catalyst-free facile synthesis of polycyclic indole ... · s1 catalyst-free facile synthesis of...

S1

Catalyst-Free Facile Synthesis of Polycyclic Indole/Pyrrole

Substituted-1,2,3-triazoles

Jitendra Gour,a Srikanth Gatadi,a Ravikumar Akunuri,a Madhavi Venkata Yaddanpudi,a N.

Jagadeesh Babu,b Mushtaq Ahmad Nengroo,c Dipak Datta,c Sidharth Chopra,d and Srinivas

Nanduri* a

aNational Institute of Pharmaceutical Education and Research (NIPER) Hyderabad 500 037,

India

bCentre for X-ray Crystallography, CSIR-Indian Institute of Chemical Technology,

Hyderabad, 500607, India

cBiochemistry Division, CSIR-Central Drug Research Institute (CDRI), Lucknow-226031,

India.

dDivision of Microbiology, CSIR-Central Drug Research Institute, Sitapur Road, Sector 10,

Janakipuram Extension, Lucknow-226031, Uttar Pradesh, India

*Corresponding author: Dr. Srinivas Nanduri; E-mail: [email protected]

Table of Contents Page

ESI/MS experiments S3

Copies of 1H and 13C NMR spectrum of compound 1u’ S4

Determination of rate limiting step S5

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2019

mailto:[email protected]

S2

Table S1: Screening of solvents S6

Table S2: Growth inhibition of the tested compounds against cancer cells S7-S9

Table S3: MIC against ESKAP pathogen panel S9-S11

X-ray crystallography information and data S12-S14

Gram-scale reaction S14

Copies of 1H and 13C NMR spectrum of compound A- D S15-S18

Copies of 1H and 13C NMR spectrum of compound 1and 3 S19-S49

Copies of 1H and 13C NMR spectrum of compound 2a-x S50-S71

Copies of 1H and 13C NMR spectrum of compound 4a-h S72-S79

S3

ESI/MS experiments:

ESI/MS experiments were performed to gain evidence for the possible intermediates in

the proposed mechanism. The experiment was conducted under the optimal reaction

condition and the reaction was monitored after 1.5 h. The ESI/MS analyses showed a

peak of intermediates, which was identified as a triazoline species. We tried to isolate and

characterize the intermediate. We could not isolate dihydrotirazole, only we were able to isolate 1u’

under optimized reaction condition. We characterized and included NMR spectrum of compound

1u’.

Figure S1: ESI/MS spectra

S4

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1u’

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1u’

9 8 7 6 5 4 3 2 1 0 ppm

2.510

3.473

3.677

4.587

7.081

7.095

7.110

7.226

7.241

7.255

7.526

7.565

7.581

7.596

7.624

7.657

7.671

7.685

7.909

7.939

7.983

8.013

8.152

8.167

2.07

2.00

1.30

1.25

1.08

4.23

1.27

1.20

1.21

2.12

8.08.1 ppm

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

39.34

39.51

39.67

39.84

40.01

40.09

40.17

40.34

42.53

51.44

105.28

111.00

121.09

121.70

122.45

124.17

127.74

128.90

129.32

132.43

133.61

135.83

138.05

138.90

188.97

S5

Determination of rate limiting step

The reaction of 1u (0.1 mmol) and sodium azide (0.13 mmol) was carried out in NMR tube

using DMSO-d6 as a solvent. The reactions were conducted for the specified time (such as 15

min, 30 min, 1 h, 2 h, 3 h, 6 h, 10 h and 20 h), then the progress of the reaction was monitored

by 1H NMR spectroscopy. Conversion of 1u to 1u’ (replacement of bromo to azide) which is

giving the corresponding cyclized product (2u) was estimated by the relative integration of

aliphatic proton( 1u: 4.82,3.82, 1u’: 4.59, 3.68 and 2u: 5.04, 4.69) and α, β-unsaturated ketone

protons. The results were listed in figure S2. We observed that the intramolecular azide-alkene

cycloaddition is slower than bromo to azide formation (1u to 1u’). Based on the result of figure

S2, it may be concluded that the intramolecular azide-alkene cycloaddition step is the rate

limiting step.

Figure S2: Progress of the reaction (1u-2u) monitored by 1H NMR (500 MHz, DMSO-d6).

S6

Table S1: Screening of solventsa

Entry Catalyst Solvent Yieldb(%)

1 None Chloroform 0

2 None DMSO 74

3 None THF 52

4 None Water Trace

5 None Methanol 61

6 None Ethanol 64

7 None Water: Methanol (2:1) Trace

8 None Water: Methanol (1:1) 11

9 None Water: Ethanol (1:1) Trace

10 None Acetone 60

11 None Water: Acetone (1:1) 86

12 None Water: Acetone (2:1) 26

13c None Water: Acetone (2:1) 56

14c None Water: Acetone (1:2) 68

14 None Water: DMF (1:1) 15

15 None Water: DMSO (1:1) 0

aReaction conditions: 1a (0.5 mmol) and NaN3 (0.6 mmol), solvent (5 mL) and the reaction was performed

at room temp for 20 h under air atmosphere. bYield of the products. Reaction was performed at room temp

for 36 h under air atmosphere

S7

Materials and Method:

Cell Lines

Multiple human cancer cell lines including HT-29 (colorectal adenocarcinoma), A549 (lung

carcinoma), PC-3 (prostate adenocarcinoma), MIA PaCa-2 (Pancreatic Carcinoma) and MCF-

7 (breast ductal carcinoma) were obtained from ATCC, USA. Early passage cells were

resuscitated from liquid nitrogen vapour stocks as needed and cultured according to the

manufacturer's instructions. Cells were routinely inspected microscopically for stable

phenotype, and all experiments were performed within early passages (within 10) of individual

cells.

Evaluation of in-vitro anticancer activity of synthetic compounds by Sulphorhodamine B

(SRB) calorimetric assay

Efficacy of the compounds as anticancer agents on various cancer cell lines was assessed using

standard Sulphorhodamine B (SRB) calorimetric assay for cytotoxicity screening as described

by before.1,2 Briefly, appropriate number of cells in 5% FBS containing medium were seeded

in 96 well plates and incubated at 37 °C in a humidified incubator with 5% CO2 until the cells

attached completely. The cells were treated with a single dose of compounds and were

incubated for further 48 hours. After an incubation period, cell monolayers were fixed with

10% (wt/vol) trichloroacetic acid followed by washing under slow running tap water. The cells

were stained with SRB dye for 30 minutes, after which the excess dye was removed by washing

3-4 times with 1% (vol/vol) acetic acid. The protein-bound dye is dissolved in 10 mM Tris

base solution for OD determination at 510 nm using a microplate reader (Epoch Microplate

Reader, Biotek, USA). Percentage of cell growth inhibition was calculated using the formula

[100-(Absorbance of compound treated cells/ Absorbance of control cells)] X 100.2

S8

References

1. Vichai, V.; Kirtikara, K., Sulforhodamine B colorimetric assay for cytotoxicity

screening. Nat. Protoc. 2006, 1 , 1112.

2. Maheshwari, S.; Avula, S. R.; Singh, A.; Singh, L. R.; Palnati, G. R.; Arya, R.

K.; Cheruvu, S. H.; Shahi, S.; Sharma, T.; Meena, S., Discovery of a Novel Small-

Molecule Inhibitor that Targets PP2A–β-Catenin Signaling and Restricts Tumor

Growth and Metastasis. Mol. Cancer Ther. 2017, 16, 1791-1805.

Table S2: Percentage Growth inhibition of the tested compounds against human cancer

cell line at 10 µM.

HT-29

(Colon)

MCF-7

(Breast) A549 (Lung) MIA PaCa-2

(Pancreatic) PC-3

(Prostate) Compound Average ± SE Average ± SE Average ± SE Average ± SE Average ± SE 2a

9.95± 6.86

21.2±3.06 8.55±5.79 10.81±0.16 9.47±0.00

2b

15.39±8.9 25.43±0.95 17.22±6.83 14.96±0.03 16.62±2.10

2c

26.91±7.07

24.89±1.33 19.97±5.99 24.84±2.33 13.27±1.38

2d

22.75±4.62

30.39±0.60 14.61±7.15 16.16±0.86 16.78±3.80

2e

7.64±3.87

20.47±0.93 9.69±8.72 0.39±2.43 8.70±0.92

2f

40.1±5.45

33.29±1.11 22.79±10.67 30.28±2.17 16.05±4.25

2g

5.71±6.59

19±5.68 8.41±10.22 20.71±12.23 18.89±4.31

2h

15.38±6.20

20.29±4.73 10.24±10.35 17.33±1.53 14.95±3.05

2i

-3.18±8.45 33.43±5.47 5.3±1.38 5.27±0.60 2.27±3.05

2j 8.1±3.24 26.31±7.16 10.86±3.18 19.87±1.39 18.53±1.47

2k

17.13±1.07 32.05±6.15 18.04±2.44 21.09±0.75 7.05±0.91

2m

7.75±1.18

23.07±0.92 13.12±3.60 7.91±1.00 3.07±0.71

2n

38.51±4.75

47.25±0.40 40.78±3.74 36.42±1.87 37.45±1.00

S9

2o

0.57±3.50

27.79±2.00 8.54±5.04 7.17±0.08 8.36±3.97

2p

3.19±4.41

27.85±6.22 16.68±10.04 7.90±4.42 11.17±0.33

2q

10.5±4.67

34.58±2.81 22.32±3.98 19.90±6.80 29.27±5.74

2r

1.59±2.70

27.4±0.65 13.27±10.46 19.97±10.22 19.67±3.82

2s

19.67±0.56

23.81±2.53 14.41±11.12 18.73±1.95 17.34±2.75

2t

-3.9±3.48

45.48±6.01 36.54±1.62 37.80±1.83 39.64±1.00

2u

-9.42±5.33

33.07±5.13 14.11±2.52 15.41±1.19 6.30±1.92

2v

-8.57±0.31

23.68±7.18 10.57±0.34 5.10±4.53 -3.20±0.51

2x

34.57±14.5

40.85±6.76 38.79±5.19 27.89±17.75 29.99±1.54

4a 21.25±0.59

39.36±7.39 29.74±2.51 14.62±4.52 20.19±0.47

4b

-13.93±3.28

18.81±2.03 12.68±1.92 26.99±13.70 -8.01±0.21

4c

NT NT NT NT

4d

-10.4±5.49

33.95±6.31 3.02±1.52 11.92±8.50 -7.34±3.90

4f

8.32±7.39

35.8±4.17 18.8±6.40 21.66±13.92 6.31±0.05

4g

-1.76±3.06

28.37±6.48 13.18±1.24 5.35±0.70 3.37±3.20

4h

-9.07±4.34

18.91±5.65 10.37±1.95 16.71±3.20 -1.61±2.43

NT = Not Tested

Antibiotic susceptibility testing against ESKAP pathogen panel

Antibiotic susceptibility testing was carried out on the newly synthesized compounds by

determining the Minimum Inhibitory Concentration (MIC) according to the standard CLSI

guidelines.3,4 MIC is defined as the minimum concentration of compound at which visible

bacterial growth is inhibited. Bacterial cultures were grown in Mueller-Hinton cation

supplemented broth (CA-MHB). Optical density (OD600) of the cultures was measured,

followed by dilution for ~106 CFU/mL. This inoculum was added into a series of test wells in

a microtitre plate that contained various concentrations of compound under test ranging from

64-0.03 µg/mL. Controls i.e., cells alone and media alone (without compound+cells) and

S10

Levofloxacin used as a reference standard. Plates were incubated at 37 °C for 16-18 h followed

by observations of MIC values by the absence or presence of visible growth. For each

compound, MIC determinations were performed independently thrice using duplicate samples

each time.

References

3. Jorgensen, J. H.; Hindler, J. F.; Reller, L. B.; Weinstein, M. P., New consensus

guidelines from the Clinical and Laboratory Standards Institute for antimicrobial

susceptibility testing of infrequently isolated or fastidious bacteria. Clin. Infect. Dis.

2007, 44, 280-286.

4. Pandey, M.; Singh, A. K.; Thakare, R.; Talwar, S.; Karaulia, P.; Dasgupta, A.;

Chopra, S.; Pandey, A. K., Diphenyleneiodonium chloride (DPIC) displays broad-

spectrum bactericidal activity. Nat. Protoc. 2017, 7, 11521.

Table S3: MIC (µg/mL) of indolo- and pyrrolo[1,4]diazepines/pyrazines against ESKAP

pathogen panel

Compound

Gram +ve Gram -ve

S. aureus

ATCC

29213

E. coli

ATCC

25922

K.

pneumoni

ae

BAA-

1705

A. baumannii

BAA 1605

P. aeruginosa

ATCC 27853

2a >64

>64 >64 >64 >64

2b 64

>64 >64 >64 >64

2c >64

>64 >64 >64 >64

2d >64

>64 >64 >64 >64

S11

2e >64 >64 >64 >64 >64

2f >64 >64 >64 >64 >64

2g 16 >64 >64 >64 >64

2h >64 >64 >64 >64 >64

2i >64 >64 >64 >64 >64

2j

>64 >64 >64 >64 >64

2k

8 >64 >64 >64 >64

2m

>64 >64 >64 >64 >64

2n

8 >64 >64 >64 >64

2o >64

>64 >64 >64 >64

2p >64 >64 >64 >64 >64

2q >64 >64 >64 >64 >64

2r >64 >64 >64 >64 >64

2s 32 >64 >64 >64 >64

2t >64 >64 >64 >64 >64

2u >64 >64 >64 >64 >64

2v >64 >64 >64 >64 >64

2x NT NT NT NT NT

4a >64 >64 >64 >64 >64

4b NT NT NT NT NT

4c >64 >64 >64 >64 >64

4d >64 >64 >64 >64 >64

4e NT NT NT NT NT

4f >64 >64 >64 >64 >64

4g >64 >64 >64 >64 >64

4h >64 >64 >64 >64 >64

Levofloxacin <0.5 <0.5 64 8 1

NT = Not Tested

S12

X-ray crystallography information and data

Figure S3. The molecular structure of KA555 (compound 2j) with the atom-numbering

scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown

as small spheres of arbitrary radius. CCDC 1887445 contains the supplementary

crystallographic data.

Sample preparation: Compound 2j was dissolved in ethanol (100 mg in 3 mL ethanol) and

allowed for crystallization at room temperature for 7-8 days.

Table S4: Crystal data and structure refinement.

Identification code KA555

Chemical formula C22H19N5O2

Molecular weight 385.42

Temperature 293(2)K

Wavelength 0.71073Å

Crystal system ; space group monoclinic ; P 21/c

Unit cell dimensions

A = 14.4652(12)Å

b = 15.665(3)Å

c = 8.435(2)Å

α = 90 °

β = 91.931(7) °

γ = 90 °

Volume 1910.2(6) Å³

Z, Calculated density 4, 1.340 g/cm³

Absorption coefficient 0.090 1/mm

F(000) 808

Theta range for data collection 2.600° to 27.500°

Limiting indices -18 <= h <= 18 ; -20 <= k <= 20 ; -10 <= l <= 10

S13

Reflection collected / unique 34927 / 4384 [R(int) = 0.0710]

Completeness to theta max 99.9 %

Refinement method Full-matrix least-square on F²

Data / restraints / parameters 4384 / 72 / 296

Goodness of fit on F² 1.172

Final R indices [I>2sigma(I)] R1 = 0.0533 ; wR2 = 0.1497

Final R indices [all data] R1 = 0.0772 ; wR2 = 0.1703

Largest diff peak and hole 0.376 and -0.251 e/Å³

Data collection and structure solution of KA555 (2j): Single crystal X-ray data for two

compounds were collected at room temperature on a Bruker D8 QUEST equipped with a four-

circle kappa diffractometer and Photon 100 detector. An Iμs microfocus Mo source

(l=0.71073Å) supplied the multi-mirror monochromated incident beam. A combination of Phi

and Omega scans were used to collect the necessary data. Unit cell dimensions were determined

using 9898 reflections. Integration and scaling of intensity data were accomplished using

SAINT program.1 The structures were solved by Direct Methods using SHELXS972 and

refinement was carried out by full-matrix least-squares technique using SHELXL-2014/7.2-3

Anisotropic displacement parameters were included for all non-hydrogen atoms. All H atoms

were positioned geometrically and treated as riding on their parent C atoms with C-H distances

of 0.93--0.97 Å, and with Uiso(H) = 1.2Ueq (C) or 1.5Ueq for methyl atoms. CCDC 1887445

contains the supplementary crystallographic data for this paper which can be obtained free of

charge at https://summary.ccdc.cam.ac.uk/structure-summary-form or from the

Cambridge Crystallographic Data Centre (CCDC), 12 Union Road, Cambridge CB2 1EZ, UK;

fax: +44(0) 1223 336 033; email: [email protected].

https://summary.ccdc.cam.ac.uk/structure-summary-form

mailto:[email protected]

S14

SMART & SAINT. Software Reference manuals. Versions 6.28a & 5.625, Bruker Analytical

X-ray Systems Inc., Madison, Wisconsin, U.S.A., 2001.

Sheldrick, G. M. SHELXS97 and SHELXL Version 2014/7, http://shelx.uni-

ac.gwdg.de/SHELX/index.php

Muller, P, Herbst-Imer, R, Spek, A. L, Schneider, T. R, and Sawaya, M. R. Crystal Structure

Refinement: A Crystallographer’s Guide to SHELXL. Muller, P. Ed. 2006 Oxford University

Press: Oxford, New York, pp. 57–91.

Scheme S1. Gram-scale reaction.

http://shelx.uni-ac.gwdg.de/SHELX/index.php

http://shelx.uni-ac.gwdg.de/SHELX/index.php

S15

1H NMR (500 MHz, DMSO-d6) spectrum of compound A

13C NMR (125 MHz, DMSO-d6) spectrum of compound A

10 9 8 7 6 5 4 3 2 1 0 ppm

2.213

2.227

2.240

2.254

2.268

2.511

2.513

3.365

3.467

3.481

3.494

4.618

4.632

4.646

7.165

7.179

7.195

7.421

7.437

7.452

7.491

7.654

7.671

7.774

7.790

9.897

9.899

2.03

2.06

2.00

1.05

1.02

0.95

1.03

1.09

1.02

200 180 160 140 120 100 80 60 40 20 0 ppm

31.72

33.82

39.54

39.71

39.88

40.04

40.21

40.38

40.54

43.24

111.38

118.32

121.39

123.84

126.39

127.30

135.50

140.26

183.78

S16

1H NMR (500 MHz, CDCl3) spectrum of compound B

13C NMR (125 MHz, CDCl3 + DMSO-d6) spectrum of compound B

10 9 8 7 6 5 4 3 2 1 0 ppm

3.656

3.670

3.684

4.864

4.878

4.891

7.178

7.181

7.191

7.194

7.197

7.208

7.210

7.244

7.300

7.301

7.418

7.420

7.431

7.435

7.437

7.448

7.450

7.458

7.475

7.725

7.739

7.741

9.854

2.18

2.18

1.06

1.06

2.17

1.02

1.00

200 180 160 140 120 100 80 60 40 20 0 ppm

35.28

44.38

44.55

44.72

44.88

45.05

45.22

50.66

82.44

82.70

82.85

82.95

115.49

123.63

126.24

128.22

131.10

132.12

139.79

145.12

187.28

S17

1H NMR (500 MHz, DMSO-d6) spectrum of compound C

13C NMR (125 MHz, DMSO-d6) spectrum of compound C

10 9 8 7 6 5 4 3 2 1 0 ppm

2.503

2.507

2.511

2.514

2.518

3.331

3.739

3.752

3.764

4.644

4.657

4.670

6.266

6.271

6.274

6.279

7.096

7.099

7.104

7.107

7.372

9.514

9.515

200 180 160 140 120 100 80 60 40 20 0 ppm

33.16

39.52

39.69

39.86

40.03

40.12

40.19

40.28

40.36

40.45

40.53

49.72

109.96

125.62

131.28

133.35

180.04

S18

1H NMR (500 MHz, DMSO-d6) spectrum of compound D

13C NMR (125 MHz, DMSO-d6) spectrum of compound D

10 9 8 7 6 5 4 3 2 1 0 ppm

2.193

2.207

2.220

2.234

2.247

2.505

2.508

2.512

3.329

3.389

3.402

3.416

4.370

4.383

4.397

6.250

6.255

6.258

6.263

7.056

7.059

7.063

7.067

7.303

9.514

2.04

2.01

2.00

0.92

0.94

0.98

0.92

180 160 140 120 100 80 60 40 20 0 ppm

31.49

34.09

39.53

39.70

39.86

40.03

40.20

40.37

40.53

47.13

110.04

125.22

131.37

132.69

179.77

S19

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1a

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1a

10 9 8 7 6 5 4 3 2 1 0 ppm

2.208

2.221

2.235

2.249

2.262

2.509

2.512

2.516

3.352

3.514

3.527

3.539

4.503

4.517

4.531

7.095

7.111

7.125

7.250

7.252

7.267

7.281

7.505

7.579

7.596

7.612

7.634

7.650

7.669

7.671

7.686

7.699

7.701

7.933

7.964

7.994

8.024

8.171

8.174

8.188

2.06

2.06

2.00

1.02

1.04

1.06

2.95

1.02

1.09

1.01

1.08

1.99

7.47.57.67.77.87.98.0 ppm

200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

31.95

33.89

39.52

39.69

39.86

40.02

40.19

40.28

40.36

40.52

41.51

105.11

110.77

120.97

121.79

122.67

124.15

127.64

128.91

129.29

132.21

133.56

135.43

138.11

138.89

188.89

S20

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1b

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1b

9 8 7 6 5 4 3 2 1 0 ppm

2.140

2.147

2.511

2.515

3.360

3.368

3.434

3.445

4.363

7.079

7.088

7.094

7.101

7.117

7.239

7.247

7.250

7.256

7.261

7.264

7.269

7.279

7.301

7.311

7.369

7.378

7.449

7.456

7.460

7.465

7.470

7.474

7.479

7.486

7.490

7.520

7.528

7.543

7.545

7.550

7.555

7.558

7.560

7.564

7.570

7.581

7.606

7.613

7.622

7.629

7.741

7.749

7.757

7.765

2.01

2.02

2.00

0.99

1.95

1.02

1.05

3.87

1.12

0.96

200 180 160 140 120 100 80 60 40 20 0 ppm

31.88

33.56

39.53

39.69

39.86

40.03

40.19

40.28

40.36

40.53

41.40

105.67

110.87

119.22

121.10

121.97

124.51

126.44

127.62

128.37

129.73

132.26

133.69

134.59

139.07

141.18

193.93

S21

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1c

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1c

11 10 9 8 7 6 5 4 3 2 1 0 ppm

2.199

2.212

2.225

2.240

2.253

2.502

2.505

2.509

2.512

2.516

3.335

3.505

3.518

3.531

4.495

4.510

4.524

7.091

7.093

7.107

7.122

7.123

7.249

7.252

7.263

7.266

7.268

7.280

7.282

7.511

7.571

7.572

7.588

7.629

7.645

7.780

7.785

7.788

7.798

7.802

7.926

7.956

7.965

7.996

8.096

8.101

8.104

8.114

8.118

8.123

2.16

2.11

2.00

1.08

1.07

1.11

1.07

1.13

2.05

1.11

1.00

2.03

200 180 160 140 120 100 80 60 40 20 0 ppm

31.94

33.88

39.54

39.70

39.87

40.04

40.20

40.29

40.37

40.46

40.54

41.50

105.35

110.80

121.01

121.84

122.25

124.27

127.63

127.69

130.92

132.33

132.66

135.35

137.11

138.95

187.98

S22

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1d

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1d

11 10 9 8 7 6 5 4 3 2 1 0 ppm

2.199

2.212

2.225

2.239

2.253

2.509

2.512

2.516

3.364

3.509

3.522

3.535

4.499

4.513

4.527

7.094

7.109

7.124

7.253

7.269

7.283

7.565

7.573

7.590

7.602

7.617

7.633

7.649

7.664

7.731

7.733

7.745

7.747

7.749

7.947

7.962

7.978

8.002

8.032

8.118

8.120

8.134

8.136

8.189

8.193

8.205

8.208

2.00

2.03

2.00

1.04

1.05

2.13

1.95

1.09

1.01

1.08

1.04

1.01

200 180 160 140 120 100 80 60 40 20 0 ppm

31.95

33.89

39.51

39.68

39.85

40.01

40.18

40.27

40.35

40.52

41.49

105.61

110.81

121.03

121.86

122.13

124.32

127.52

127.63

128.56

131.23

132.92

133.24

134.34

135.32

138.98

139.95

187.61

S23

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1e

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1e

9 8 7 6 5 4 3 2 1 0 ppm

1.909

1.921

1.932

2.512

3.182

3.192

3.212

3.224

3.235

3.364

4.397

4.410

4.422

6.171

6.647

6.664

7.064

7.078

7.093

7.203

7.218

7.233

7.361

7.488

7.505

7.594

7.610

7.788

7.819

7.907

7.942

7.960

2.13

2.22

2.11

2.05

2.00

0.98

1.05

1.04

1.06

0.98

1.01

3.01

200 180 160 140 120 100 80 60 40 20 0 ppm

30.67

39.50

39.66

39.83

40.00

40.17

40.33

40.50

49.08

58.39

103.67

110.64

113.26

120.62

121.41

123.09

123.49

125.86

127.68

129.96

131.49

136.10

138.60

154.34

185.72

S24

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1f

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1f

9 8 7 6 5 4 3 2 1 0 ppm

0.880

0.893

1.863

1.877

1.890

1.904

1.917

1.931

1.944

2.203

2.216

2.230

2.244

2.257

2.506

2.510

2.513

2.548

2.563

3.336

3.510

3.523

3.535

4.496

4.511

4.524

7.090

7.104

7.119

7.242

7.244

7.258

7.272

7.274

7.355

7.372

7.483

7.572

7.589

7.626

7.641

7.909

7.940

7.979

8.009

8.091

8.107

6.03

1.03

2.05

2.17

1.97

2.00

1.01

1.04

2.00

0.97

1.02

1.01

1.01

1.04

1.97

200 180 160 140 120 100 80 60 40 20 0 ppm

22.60

30.01

31.92

33.90

39.53

39.70

39.87

40.03

40.20

40.29

40.37

40.46

40.53

41.51

44.96

104.91

110.74

120.93

121.74

122.82

124.06

127.66

128.93

129.83

131.82

135.50

135.91

138.84

147.47

188.41

S25

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1g

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1g

10 9 8 7 6 5 4 3 2 1 ppm

1.901

1.914

1.926

1.938

1.951

2.510

3.200

3.212

3.223

3.348

4.416

4.429

4.443

7.067

7.072

7.076

7.083

7.090

7.106

7.229

7.245

7.259

7.379

7.394

7.410

7.458

7.485

7.489

7.493

7.510

7.526

7.614

7.629

7.644

7.659

7.905

9.816

2.04

2.13

2.00

2.05

1.05

1.07

0.98

1.01

1.05

1.05

1.03

2.03

1.02

200 180 160 140 120 100 80 60 40 20 0 ppm

30.62

39.53

39.69

39.86

40.03

40.20

40.28

40.36

40.45

40.53

58.36

68.81

104.79

110.79

115.02

119.91

120.69

120.79

121.69

122.42

124.00

127.62

130.32

132.32

135.61

138.89

139.62

158.24

188.83

S26

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1h

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1h

9 8 7 6 5 4 3 2 1 0 ppm

2.205

2.217

2.231

2.244

2.257

2.513

3.382

3.505

3.518

3.531

3.885

4.489

4.503

4.517

7.092

7.106

7.123

7.239

7.255

7.269

7.486

7.565

7.582

7.629

7.644

7.658

7.661

7.911

7.929

7.933

7.939

8.006

8.037

2.08

2.09

5.99

2.00

2.01

1.14

1.19

1.10

2.10

1.94

1.05

200 180 160 140 120 100 80 60 40 20 0 ppm

31.92

33.88

39.52

39.69

39.86

40.03

40.19

40.36

40.53

41.50

56.08

56.24

104.71

110.70

111.26

111.40

120.90

121.66

122.77

123.69

123.95

127.68

131.05

131.25

135.62

138.78

149.31

153.70

187.08

S27

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1i

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1i

10 9 8 7 6 5 4 3 2 1 0 ppm

2.203

2.216

2.230

2.244

2.256

2.507

2.510

2.514

3.344

3.513

3.525

3.538

4.502

4.517

4.531

7.094

7.109

7.124

7.250

7.251

7.266

7.280

7.401

7.418

7.436

7.512

7.522

7.556

7.577

7.593

7.632

7.648

7.926

7.957

7.973

8.002

8.033

8.242

8.260

8.264

8.271

8.278

8.285

8.289

2.02

2.00

2.03

1.04

1.07

2.09

1.09

1.05

1.08

1.01

1.03

2.04

200 180 160 140 120 100 80 60 40 20 0 ppm

31.96

33.89

39.51

39.68

39.85

40.01

40.10

40.18

40.27

40.35

40.44

40.51

40.60

41.49

105.18

110.78

116.21

116.39

120.98

121.80

122.41

124.19

127.62

131.86

131.94

132.35

134.77

134.79

135.39

138.89

164.51

166.51

187.41

S28

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1j

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1j

11 10 9 8 7 6 5 4 3 2 1 0 ppm

2.094

2.209

2.222

2.236

2.250

2.263

2.510

3.338

3.514

3.527

3.539

4.504

4.518

4.532

7.095

7.110

7.125

7.253

7.268

7.283

7.453

7.504

7.520

7.535

7.579

7.596

7.632

7.648

7.868

7.878

7.899

7.920

7.951

8.260

10.180

3.11

2.03

1.98

2.00

1.05

1.04

1.02

1.15

0.98

1.09

4.19

1.02

1.08

200 180 160 140 120 100 80 60 40 20 0 ppm

24.50

31.95

33.88

39.50

39.67

39.84

40.01

40.09

40.17

40.26

40.34

40.43

40.51

40.60

41.52

104.96

110.78

118.94

120.99

121.81

122.76

123.78

123.93

124.18

127.63

129.69

132.32

135.39

138.62

138.90

140.30

169.09

188.85

S29

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1k

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1k

9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

2.198

2.211

2.225

2.239

2.251

2.511

2.514

3.354

3.507

3.520

3.532

4.498

4.512

4.526

7.096

7.111

7.126

7.258

7.273

7.288

7.540

7.576

7.593

7.637

7.653

7.934

7.950

7.985

7.990

8.021

8.330

8.347

2.06

2.00

2.01

1.00

1.01

0.96

1.03

1.00

3.93

1.90

200 180 160 140 120 100 80 60 40 20 0 ppm

31.94

33.86

39.51

39.68

39.84

40.01

40.10

40.18

40.27

40.34

40.43

40.51

40.60

41.49

105.63

110.83

121.05

121.91

122.28

123.24

124.40

125.41

126.19

126.22

127.61

129.65

132.42

132.67

132.93

133.18

133.27

135.24

139.03

141.38

188.31

S30

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1m

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1m

9 8 7 6 5 4 3 2 1 0 ppm

2.248

2.261

2.274

2.289

2.301

2.464

2.551

2.554

2.557

3.386

3.558

3.571

3.584

4.543

4.557

4.571

7.136

7.151

7.166

7.289

7.305

7.320

7.433

7.449

7.538

7.547

7.619

7.635

7.671

7.687

7.952

7.983

8.030

8.061

8.129

8.145

2.13

3.09

2.19

2.00

1.16

1.22

2.14

1.13

1.08

1.09

1.16

1.10

2.04

200 180 160 140 120 100 80 60 40 20 0 ppm

21.68

31.95

33.90

39.52

39.69

39.85

40.02

40.19

40.36

40.52

41.51

104.92

110.75

120.94

121.74

122.74

124.07

127.66

129.06

129.86

131.83

135.50

135.59

138.84

144.01

188.29

S31

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1n

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1n

10 9 8 7 6 5 4 3 2 1 0 ppm

2.189

2.202

2.216

2.231

2.243

2.502

2.505

2.509

2.512

2.516

3.335

3.503

3.516

3.528

4.500

4.515

4.529

7.118

7.123

7.136

7.141

7.155

7.160

7.406

7.410

7.425

7.430

7.511

7.605

7.614

7.623

7.632

7.926

7.944

7.957

7.960

8.007

8.037

8.336

8.352

2.00

2.02

2.00

0.98

0.96

0.96

1.00

2.92

1.07

2.02

200 180 160 140 120 100 80 60 40 20 0 ppm

31.87

33.88

39.51

39.68

39.84

40.01

40.10

40.18

40.27

40.34

40.43

40.51

40.60

41.75

105.15

105.19

105.86

106.05

112.15

112.23

112.74

112.96

123.12

125.40

126.22

126.25

127.64

127.72

129.71

132.48

132.74

132.91

132.99

135.73

136.83

141.26

157.16

159.02

188.38

S32

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1o

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1o

10 9 8 7 6 5 4 3 2 1 0 ppm

2.188

2.200

2.215

2.228

2.241

2.507

2.511

2.514

3.492

3.505

3.517

4.478

4.492

4.506

7.084

7.099

7.114

7.240

7.256

7.270

7.511

7.526

7.542

7.549

7.570

7.606

7.622

7.638

7.832

7.834

7.836

7.848

7.850

7.852

7.937

7.968

7.980

8.011

8.149

8.164

8.324

8.327

8.331

2.10

2.01

2.00

1.03

1.04

3.02

1.13

1.01

0.90

1.11

0.96

0.92

180 160 140 120 100 80 60 40 20 0 ppm

31.91

33.88

39.54

39.70

39.87

40.04

40.20

40.37

40.54

41.49

105.64

110.78

121.01

121.86

122.07

122.84

124.31

127.64

127.86

131.42

132.88

135.31

136.09

138.98

140.13

187.50

S33

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1p

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1p

9 8 7 6 5 4 3 2 1 0 ppm

2.509

2.512

3.321

3.821

3.834

3.846

4.837

4.849

4.862

7.112

7.126

7.141

7.255

7.269

7.284

7.549

7.565

7.581

7.587

7.607

7.624

7.640

7.655

7.880

7.896

7.943

7.973

7.992

8.022

8.167

8.183

8.341

2.10

2.00

1.13

1.23

4.39

1.07

1.04

1.20

1.01

1.00

200 180 160 140 120 100 80 60 40 20 0 ppm

32.87

39.53

39.70

39.86

40.03

40.12

40.20

40.29

40.37

40.46

40.53

40.62

44.35

105.67

111.22

121.19

121.75

121.95

122.82

124.29

127.69

127.91

131.43

131.52

133.35

135.73

136.16

138.89

140.17

187.64

S34

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1q

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1q

9 8 7 6 5 4 3 2 1 0 ppm

0.887

0.900

1.871

1.885

1.898

1.912

1.925

1.939

1.952

2.509

2.512

2.515

2.557

2.572

3.348

3.818

3.830

3.843

4.825

4.838

4.850

7.106

7.121

7.136

7.242

7.258

7.273

7.329

7.365

7.382

7.505

7.599

7.616

7.634

7.649

7.914

7.945

7.983

8.013

8.103

8.120

6.24

1.05

2.20

2.02

2.00

1.02

1.06

2.02

1.04

0.95

0.99

1.08

1.04

2.06

200 180 160 140 120 100 80 60 40 20 0 ppm

22.61

30.03

32.82

39.50

39.66

39.83

40.00

40.16

40.25

40.33

40.42

40.50

44.35

44.96

104.98

111.14

121.11

121.64

122.56

124.05

127.71

128.95

129.85

132.18

135.90

138.73

147.51

188.40

S35

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1r

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1r

11 10 9 8 7 6 5 4 3 2 1 0 ppm

2.505

2.509

2.512

3.349

3.817

3.829

3.842

4.829

4.841

4.854

7.108

7.123

7.138

7.249

7.251

7.265

7.280

7.281

7.582

7.598

7.605

7.614

7.621

7.637

7.654

7.732

7.734

7.736

7.748

7.750

7.752

7.948

7.979

7.995

8.026

8.125

8.141

8.207

8.211

8.214

2.11

2.00

1.11

1.09

4.23

1.05

1.05

1.13

1.01

1.04

200 180 160 140 120 100 80 60 40 20 0 ppm

32.85

39.52

39.69

39.86

40.03

40.19

40.28

40.36

40.45

40.53

44.34

105.65

111.19

121.19

121.75

121.95

124.29

127.53

127.69

128.57

131.24

133.25

133.32

134.34

135.73

138.88

139.96

187.67

S36

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1s

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1s

9 8 7 6 5 4 3 2 1 0 ppm

2.513

3.336

3.806

3.818

3.831

3.878

3.909

3.952

4.783

4.795

4.807

6.664

6.668

6.681

6.685

6.718

6.722

7.094

7.109

7.124

7.223

7.245

7.259

7.590

7.607

7.613

7.620

7.629

7.651

7.665

7.683

7.746

7.777

2.18

3.00

3.03

2.00

0.97

0.95

1.07

2.05

4.10

1.21

200 180 160 140 120 100 80 60 40 20 0 ppm

32.55

39.52

39.69

39.86

40.03

40.12

40.19

40.28

40.36

40.45

40.53

40.61

44.46

56.12

56.53

99.11

104.38

106.62

111.03

121.02

121.52

121.82

123.85

127.71

129.94

132.67

135.97

138.72

160.80

164.56

188.85

S37

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1t

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1t

10 9 8 7 6 5 4 3 2 1 0 ppm

2.507

2.511

2.514

3.343

3.819

3.831

3.843

4.825

4.837

4.849

7.069

7.073

7.085

7.089

7.105

7.120

7.134

7.242

7.244

7.258

7.273

7.382

7.398

7.413

7.491

7.494

7.504

7.602

7.619

7.628

7.644

7.651

7.667

7.913

9.817

2.07

2.00

0.93

1.02

1.06

1.06

1.97

3.17

2.16

1.09

200 180 160 140 120 100 80 60 40 20 0 ppm

32.80

39.51

39.68

39.84

40.01

40.10

40.18

40.27

40.35

40.43

40.51

44.35

105.03

111.15

115.03

119.98

120.74

121.11

121.66

122.63

124.08

127.71

130.34

132.37

135.83

138.76

139.56

158.24

188.82

S38

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1u

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1u

10 9 8 7 6 5 4 3 2 1 0 ppm

2.510

2.513

3.346

3.824

3.837

3.849

4.832

4.844

4.856

7.111

7.126

7.141

7.249

7.263

7.265

7.279

7.525

7.586

7.602

7.618

7.640

7.656

7.675

7.677

7.691

7.704

7.707

7.934

7.965

7.973

7.975

7.991

8.021

8.178

8.195

2.00

1.99

1.06

1.03

1.19

4.17

1.16

1.02

1.18

2.00

200 180 160 140 120 100 80 60 40 20 0 ppm

32.81

39.53

39.70

39.87

40.03

40.20

40.37

40.53

44.37

105.17

111.16

121.14

121.69

122.47

124.13

127.71

128.92

129.30

132.59

133.57

135.83

138.13

138.80

188.93

S39

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1v

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1v

9 8 7 6 5 4 3 2 1 0 ppm

0.915

0.920

0.930

0.945

1.598

1.612

1.627

1.642

2.197

2.211

2.225

2.502

2.506

2.510

2.513

2.517

2.703

2.717

2.731

3.329

3.496

3.508

3.521

4.480

4.494

4.508

6.918

6.950

7.070

7.072

7.086

7.100

7.101

7.195

7.223

7.225

7.237

7.239

7.242

7.253

7.255

7.551

7.552

7.568

7.587

7.603

7.716

7.748

2.99

2.10

2.00

2.00

2.06

2.00

1.08

1.15

0.96

1.08

0.99

1.03

1.01

200 180 160 140 120 100 80 60 40 20 0 ppm

14.17

17.83

32.03

33.81

39.53

39.69

39.86

40.03

40.12

40.19

40.28

40.36

40.45

40.53

40.62

41.40

42.24

104.07

110.68

120.85

121.64

123.85

127.12

127.42

128.62

130.31

135.07

138.71

199.90

S40

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1w

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1w

11 10 9 8 7 6 5 4 3 2 1 0 ppm

1.796

1.802

1.808

2.502

2.506

2.510

2.513

2.517

3.333

3.519

3.531

3.544

4.433

4.446

7.087

7.092

7.105

7.110

7.124

7.129

7.381

7.386

7.401

7.406

7.464

7.582

7.586

7.597

7.613

7.623

7.633

7.642

7.674

7.677

7.679

7.688

7.691

7.695

7.704

7.706

7.708

7.873

7.904

8.004

8.034

8.170

8.172

8.187

4.12

2.05

2.06

1.00

0.99

0.98

3.04

1.03

1.02

1.04

1.99

200 180 160 140 120 100 80 60 40 20 0 ppm

29.58

30.03

34.92

39.53

39.70

39.87

40.03

40.20

40.29

40.37

40.53

42.41

104.46

104.50

105.65

105.83

112.25

112.33

112.55

123.32

127.56

127.65

128.94

129.31

132.00

133.65

135.69

136.98

138.02

157.07

158.93

188.94

S41

1H NMR (500 MHz, DMSO-d6) spectrum of compound 1x

13C NMR (125 MHz, DMSO-d6) spectrum of compound 1x

9 8 7 6 5 4 3 2 1 0 ppm

0.919

0.934

0.948

1.599

1.614

1.628

1.643

2.506

2.510

2.513

2.707

2.721

2.736

3.323

3.797

3.809

3.821

4.823

4.836

4.848

6.906

6.938

7.082

7.097

7.111

7.213

7.218

7.234

7.249

7.251

7.571

7.588

7.606

7.733

7.765

3.07

2.23

2.08

2.13

2.00

1.12

1.33

2.09

2.20

1.15

200 180 160 140 120 100 80 60 40 20 0 ppm

14.17

17.82

32.95

39.52

39.69

39.86

40.03

40.12

40.19

40.28

40.36

40.45

40.53

40.62

42.16

44.23

104.03

111.06

121.01

121.52

123.80

127.25

127.69

130.75

135.47

138.63

200.00

S42



8 7 6 5 4 3 2 1 0 ppm

2.511

3.329

3.758

3.770

3.782

4.537

4.550

4.562

6.255

7.122

7.127

7.213

7.545

7.560

7.575

7.589

7.630

7.645

7.659

7.720

7.750

8.090

8.105

2.26

2.00

1.05

0.92

0.91

3.06

1.12

1.12

1.96

200 180 160 140 120 100 80 60 40 20 0 ppm

33.69

39.53

39.70

39.87

40.03

40.20

40.29

40.37

40.46

40.53

47.85

110.35

113.78

116.88

128.49

128.61

129.15

129.67

132.28

133.08

138.64

188.83

S43

1H NMR (500 MHz, DMSO-d6) spectrum of compound 3b

13C NMR (125 MHz, DMSO-d6) spectrum of compound 3b

9 8 7 6 5 4 3 2 1 0 ppm

2.504

2.507

2.511

2.514

2.517

3.327

3.754

3.767

3.779

4.537

4.550

4.562

6.250

6.256

6.263

7.126

7.129

7.133

7.136

7.211

7.215

7.219

7.362

7.380

7.397

7.564

7.594

7.715

7.745

8.177

8.188

8.194

8.206

2.00

2.06

0.93

0.93

0.93

1.96

1.03

1.09

1.93

200 180 160 140 120 100 80 60 40 20 0 ppm

33.76

39.50

39.67

39.84

40.00

40.09

40.17

40.26

40.34

40.43

40.50

40.60

47.82

110.39

113.89

116.04

116.21

116.57

128.57

129.66

131.50

131.58

132.45

135.28

164.23

166.23

187.36

S44



10 9 8 7 6 5 4 3 2 1 0 ppm

2.506

2.510

2.514

3.351

3.751

3.764

3.776

4.539

4.551

4.563

6.258

6.264

6.265

6.271

7.180

7.183

7.188

7.191

7.224

7.229

7.232

7.497

7.512

7.528

7.553

7.583

7.745

7.775

7.810

7.812

7.814

7.815

7.826

7.827

7.830

7.831

8.089

8.105

8.231

8.234

2.08

2.08

0.98

0.99

1.03

1.01

1.01

1.07

0.98

1.06

1.00

7.37.47.57.67.77.8 ppm

200 180 160 140 120 100 80 60 40 20 0 ppm

33.72

36.70

39.53

39.70

39.86

40.03

40.20

40.29

40.37

40.53

47.85

110.51

114.37

116.31

122.73

127.61

128.87

129.69

131.13

131.33

133.00

135.65

140.70

187.40

S45

1H NMR (500 MHz, CDCl3) spectrum of compound 3d

13C NMR (125 MHz, CDCl3) spectrum of compound 3d

10 9 8 7 6 5 4 3 2 1 0 ppm

-0.000

1.642

3.591

3.604

3.618

4.461

4.474

4.488

6.315

6.321

6.328

6.982

6.990

6.994

7.265

7.300

7.330

7.684

7.700

7.716

7.821

7.850

8.333

8.349

8.404

8.406

8.408

8.420

8.422

8.424

8.822

1.98

2.00

1.03

1.96

1.16

1.03

1.05

0.98

1.00

0.94

200 180 160 140 120 100 80 60 40 20 0 ppm

30.64

48.45

76.78

77.03

77.28

110.88

114.15

115.61

123.03

126.75

128.21

129.12

129.81

132.84

133.87

140.01

148.45

187.03

S46



9 8 7 6 5 4 3 2 1 0 ppm

2.182

2.195

2.209

2.223

2.236

2.506

2.510

2.514

3.339

3.433

3.446

3.459

4.243

4.257

4.271

6.244

6.251

6.257

7.166

7.174

7.498

7.514

7.530

7.546

7.576

7.759

7.789

7.816

7.818

7.832

8.082

8.098

8.224

8.228

8.231

2.11

2.06

2.03

0.98

1.97

0.95

1.01

0.99

0.99

1.01

1.00

200 180 160 140 120 100 80 60 40 20 0 ppm

31.66

34.69

39.54

39.70

39.87

40.04

40.20

40.37

40.54

45.05

110.53

114.45

116.31

122.71

127.61

128.66

129.46

131.10

131.36

132.95

135.64

140.73

187.44

S47

1H NMR (500 MHz, DMSO-d6) spectrum of compound 3f

13C NMR (125 MHz, DMSO-d6) spectrum of compound 3f

9 8 7 6 5 4 3 2 1 0 ppm

2.183

2.196

2.210

2.223

2.236

2.502

2.505

2.509

2.513

2.516

3.346

3.430

3.443

3.456

4.245

4.260

4.273

6.252

6.257

6.259

6.264

7.149

7.152

7.157

7.160

7.175

7.180

7.183

7.547

7.577

7.778

7.808

7.889

7.905

8.248

8.264

2.09

2.14

2.07

0.96

2.01

0.97

1.06

2.08

2.00

200 180 160 140 120 100 80 60 40 20 0 ppm

31.61

34.68

39.52

39.69

39.86

40.02

40.19

40.28

40.36

40.45

40.53

45.05

110.61

114.45

116.48

121.11

123.28

125.45

126.01

126.04

126.07

127.61

128.83

129.10

129.33

129.42

132.03

132.29

132.54

132.79

133.25

141.99

188.15

S48

1H NMR (500 MHz, DMSO-d6) spectrum of compound 3g

13C NMR (125 MHz, DMSO-d6) spectrum of compound 3g

9 8 7 6 5 4 3 2 1 0 ppm

2.181

2.194

2.208

2.221

2.234

2.506

2.510

2.513

3.350

3.353

3.432

3.445

3.457

4.243

4.257

4.271

6.245

6.252

6.258

7.164

7.168

7.175

7.550

7.556

7.564

7.580

7.585

7.595

7.682

7.684

7.698

7.700

7.764

7.794

8.042

8.058

8.097

8.100

8.104

2.17

2.11

2.00

1.04

2.01

2.17

1.24

1.03

0.99

0.96

200 180 160 140 120 100 80 60 40 20 0 ppm

31.64

34.69

39.53

39.70

39.87

40.03

40.20

40.37

40.53

45.05

110.53

114.42

116.33

127.23

128.24

128.65

129.46

131.09

132.73

132.94

134.20

140.53

187.50

S49



9 8 7 6 5 4 3 2 1 0 ppm

2.184

2.197

2.211

2.224

2.237

2.508

2.511

2.514

3.350

3.437

3.449

3.462

3.836

3.845

3.859

3.868

4.237

4.250

4.264

6.224

6.230

6.237

7.077

7.094

7.101

7.116

7.120

7.559

7.569

7.584

7.587

7.600

7.709

7.739

7.807

7.811

7.824

7.828

2.05

2.06

6.05

2.00

1.10

3.36

2.05

1.01

1.09

200 180 160 140 120 100 80 60 40 20 0 ppm

31.71

34.68

39.53

39.69

39.86

40.03

40.12

40.19

40.28

40.36

40.45

40.53

45.03

56.06

56.22

110.16

111.19

111.38

113.43

117.00

123.16

127.83

129.53

131.32

131.51

149.19

153.29

187.21

S50

1H NMR (500 MHz, CDCl3) spectrum of compound 2a

13C NMR (125 MHz, CDCl3) spectrum of compound 2a

9 8 7 6 5 4 3 2 1 0 ppm

-0.000

2.598

2.612

2.625

2.639

2.652

4.245

4.258

4.272

4.625

4.639

4.652

7.162

7.176

7.192

7.256

7.257

7.314

7.329

7.331

7.345

7.372

7.389

7.498

7.514

7.529

7.588

7.604

7.623

7.736

7.752

8.303

8.318

8.319

2.02

2.08

2.00

0.95

0.96

1.04

2.00

1.92

1.00

1.94

200 180 160 140 120 100 80 60 40 20 0 ppm

28.92

40.75

46.60

76.79

77.05

77.30

109.00

109.78

120.62

122.42

124.10

124.95

127.60

128.31

130.74

133.08

134.75

137.23

138.15

143.74

186.25

S51

1H NMR (500 MHz, CDCl3) spectrum of compound 2b

13C NMR (125 MHz, CDCl3) spectrum of compound 2b

9 8 7 6 5 4 3 2 1 0 ppm

0.000

2.573

2.586

2.599

2.613

2.626

4.243

4.256

4.270

4.591

4.604

4.618

7.162

7.177

7.192

7.249

7.317

7.332

7.346

7.348

7.369

7.385

7.397

7.399

7.412

7.414

7.427

7.429

7.553

7.556

7.568

7.571

7.614

7.625

7.723

7.739

2.10

2.03

2.00

1.00

4.19

1.02

1.90

1.04

200 180 160 140 120 100 80 60 40 20 0 ppm

28.75

41.12

46.82

76.83

77.09

77.34

109.17

110.17

120.14

120.77

122.45

124.37

124.59

127.12

127.61

130.05

131.67

133.36

134.47

138.41

140.53

143.04

188.02

S52

1H NMR (500 MHz, CDCl3) spectrum of compound 2c

13C NMR (125 MHz, CDCl3) spectrum of compound 2c

9 8 7 6 5 4 3 2 1 0 ppm

0.000

2.519

2.533

2.546

2.559

2.572

4.160

4.173

4.186

4.541

4.555

4.568

7.089

7.103

7.118

7.178

7.242

7.257

7.272

7.293

7.309

7.547

7.567

7.584

7.662

7.678

8.142

8.159

2.06

2.10

2.06

1.01

2.19

3.05

1.00

2.06

200 180 160 140 120 100 80 60 40 20 0 ppm

-0.00

27.90

39.75

45.63

75.77

76.02

76.28

108.00

108.97

119.68

121.43

123.22

123.77

126.56

127.32

130.59

131.27

133.96

134.99

137.20

142.41

183.86

S53

1H NMR (500 MHz, DMSO-d6) spectrum of compound 2d

13C NMR (125 MHz, DMSO-d6) spectrum of compound 2d

9 8 7 6 5 4 3 2 1 0 ppm

2.512

2.544

2.558

2.571

2.584

3.336

4.375

4.387

4.400

4.657

4.670

4.684

7.147

7.162

7.304

7.319

7.334

7.460

7.619

7.635

7.651

7.694

7.711

7.729

7.745

7.770

7.785

8.094

8.109

8.175

2.26

2.08

2.00

1.06

1.03

1.00

1.02

3.07

0.96

0.92

200 180 160 140 120 100 80 60 40 20 0 ppm

28.62

39.51

39.68

39.85

40.01

40.10

40.18

40.27

40.35

40.43

40.51

41.17

47.35

108.79

110.73

120.72

122.00

124.12

125.12

127.13

129.23

130.47

130.89

133.27

133.57

134.85

138.41

139.43

143.04

185.08

S54



8 7 6 5 4 3 2 1 0 ppm

2.512

2.544

2.557

2.569

3.341

4.356

4.368

4.380

4.654

4.667

4.680

5.390

6.855

6.870

7.115

7.129

7.144

7.178

7.194

7.209

7.263

7.281

7.299

7.320

7.411

7.676

7.693

7.709

2.25

2.06

2.00

1.95

0.96

1.24

1.12

3.93

2.04

4.24.44.64.85.05.25.4 ppm

200 180 160 140 120 100 80 60 40 20 0 ppm

28.42

39.56

39.73

39.89

40.06

40.23

40.39

40.56

41.54

47.50

63.29

107.98

110.67

115.41

118.64

119.18

120.66

121.86

123.89

125.36

127.22

129.21

133.63

138.22

138.33

143.82

149.22

187.57

S55

1H NMR (500 MHz, CDCl3) spectrum of compound 2f

13C NMR (125 MHz, CDCl3) spectrum of compound 2f

9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

0.000

0.919

0.932

1.864

1.875

1.888

1.902

1.915

1.929

1.942

1.956

1.970

1.983

2.549

2.563

2.591

2.604

2.618

2.631

2.645

4.239

4.252

4.265

4.621

4.634

4.648

7.152

7.154

7.168

7.182

7.184

7.255

7.274

7.291

7.295

7.303

7.305

7.320

7.322

7.334

7.336

7.364

7.380

7.598

7.724

7.740

8.235

8.251

2.82

2.93

1.05

2.01

2.02

2.00

2.00

1.04

2.03

1.11

1.04

0.93

1.01

1.91

2.02.12.22.32.42.52.62.7 ppm

200 180 160 140 120 100 80 60 40 20 0 ppm

22.38

28.91

30.09

40.76

45.53

46.58

76.76

77.02

77.22

77.27

108.95

109.64

120.57

122.39

124.00

125.06

127.65

129.09

130.76

134.50

134.93

138.13

143.98

147.67

185.89

S56

1H NMR (500 MHz, CDCl3) spectrum of compound 2g

13C NMR (125 MHz, CDCl3) spectrum of compound 2g

9 8 7 6 5 4 3 2 1 0 ppm

0.006

2.584

2.598

2.611

2.625

2.638

4.237

4.250

4.263

4.613

4.626

4.640

7.072

7.073

7.077

7.088

7.090

7.093

7.118

7.158

7.174

7.188

7.258

7.313

7.330

7.346

7.363

7.378

7.588

7.726

7.742

7.787

7.790

7.794

7.851

7.866

2.03

2.02

2.00

1.04

1.07

1.36

1.93

0.93

0.97

0.96

1.04

200 180 160 140 120 100 80 60 40 20 0 ppm

-0.03

28.88

40.74

46.65

76.75

77.00

77.20

77.25

108.98

109.81

117.20

120.53

120.65

122.43

123.30

124.15

124.80

127.60

129.62

134.80

138.17

138.49

143.65

155.79

185.78

S57



9 8 7 6 5 4 3 2 1 0 ppm

2.505

2.508

2.512

2.515

2.533

2.546

2.559

3.321

3.642

3.840

4.339

4.352

4.365

4.616

4.629

4.642

6.595

6.599

6.629

6.633

6.646

6.650

7.103

7.104

7.118

7.133

7.184

7.274

7.276

7.291

7.293

7.305

7.307

7.515

7.532

7.645

7.661

7.667

7.684

2.10

3.00

3.00

2.04

2.04

0.94

1.06

1.00

0.97

1.03

1.00

2.03

200 180 160 140 120 100 80 60 40 20 0 ppm

33.19

44.32

44.48

44.65

44.82

44.99

45.07

45.15

45.32

46.38

52.07

60.81

60.96

103.94

110.54

112.49

115.48

125.48

126.43

126.71

128.62

130.17

131.99

137.20

137.45

143.01

149.75

165.34

168.90

191.55

S58

1H NMR (500 MHz, CDCl3) spectrum of compound 2i

13C NMR (125 MHz, CDCl3) spectrum of compound 2i

10 9 8 7 6 5 4 3 2 1 0 ppm

-0.000

2.605

2.618

2.631

2.645

2.658

2.782

4.247

4.260

4.273

4.628

4.642

4.656

7.168

7.182

7.185

7.198

7.202

7.257

7.319

7.321

7.336

7.338

7.350

7.351

7.375

7.391

7.618

7.741

7.757

8.393

8.397

8.403

8.410

8.417

8.421

2.03

2.01

2.00

2.95

1.01

1.06

0.96

0.98

1.95

200 180 160 140 120 100 80 60 40 20 0 ppm

-0.00

28.95

40.76

46.64

76.77

77.03

77.28

109.00

109.91

115.35

115.53

120.69

122.46

124.19

124.88

127.62

133.47

133.54

134.89

138.20

143.61

164.86

166.89

184.41

S59

1H NMR (500 MHz, DMSO-d6) spectrum of compound 2j

13C NMR (125 MHz, DMSO-d6) spectrum of compound 2j

11 10 9 8 7 6 5 4 3 2 1 0 ppm

2.087

2.505

2.508

2.512

2.537

2.550

2.564

2.577

2.590

3.348

4.357

4.370

4.383

4.656

4.669

4.683

7.117

7.132

7.146

7.286

7.301

7.315

7.403

7.479

7.495

7.511

7.671

7.688

7.704

7.720

7.823

7.839

7.922

7.938

8.355

10.192

3.09

2.04

2.05

2.00

1.08

1.08

1.07

1.09

2.15

1.10

1.04

0.97

1.05

200 180 160 140 120 100 80 60 40 20 0 ppm

24.45

28.51

39.56

39.73

39.89

40.06

40.23

40.39

40.56

41.42

47.46

108.45

110.67

120.68

120.94

121.93

124.00

124.08

125.24

125.64

127.21

129.17

134.28

138.02

138.38

139.88

143.40

169.07

186.56

S60

1H NMR (500 MHz, CDCl3) spectrum of compound 2k

13C NMR (125 MHz, CDCl3) spectrum of compound 2k

10 9 8 7 6 5 4 3 2 1 0 ppm

-0.000

2.617

2.631

2.644

2.658

2.671

4.260

4.273

4.286

4.640

4.653

4.667

7.178

7.181

7.192

7.194

7.196

7.208

7.210

7.255

7.334

7.336

7.348

7.351

7.353

7.364

7.367

7.385

7.386

7.401

7.402

7.662

7.663

7.747

7.755

7.771

7.787

8.422

8.438

2.00

2.02

2.00

1.07

1.07

1.17

1.01

3.04

1.92

200 180 160 140 120 100 80 60 40 20 0 ppm

-0.01

28.92

40.77

46.69

76.78

77.03

77.28

109.05

110.21

120.78

122.50

122.68

124.38

124.64

124.85

125.23

125.26

125.29

125.32

127.54

130.98

133.73

133.99

134.25

134.51

135.29

138.28

140.16

143.18

185.02

S61

1H NMR (500 MHz, CDCl3) spectrum of compound 2m

13C NMR (125 MHz, CDCl3) spectrum of compound 2m

9 8 7 6 5 4 3 2 1 0 ppm

0.000

2.431

2.579

2.592

2.606

2.619

2.632

4.227

4.240

4.254

4.607

4.620

4.634

7.149

7.163

7.178

7.252

7.298

7.314

7.328

7.356

7.373

7.601

7.721

7.737

8.214

8.231

3.03

2.00

2.05

2.02

1.06

2.91

1.10

0.92

1.00

1.90

200 180 160 140 120 100 80 60 40 20 0 ppm

21.72

28.91

40.79

46.60

76.80

77.05

77.31

108.98

109.65

120.58

122.38

124.02

125.06

127.64

129.04

130.89

134.51

134.71

138.14

143.94

143.96

185.88

S62

1H NMR (500 MHz, CDCl3) spectrum of compound 2n

13C NMR (125 MHz, CDCl3) spectrum of compound 2n

9 8 7 6 5 4 3 2 1 0 ppm

-0.000

2.631

2.644

2.658

2.672

2.685

4.245

4.258

4.271

4.658

4.672

4.685

7.086

7.091

7.104

7.109

7.122

7.127

7.260

7.302

7.310

7.320

7.328

7.385

7.390

7.403

7.408

7.606

7.776

7.793

8.425

8.441

2.13

2.16

2.00

1.14

1.18

1.10

1.01

2.20

2.04

200 180 160 140 120 100 80 60 40 20 0 ppm

-0.04

28.92

41.13

46.67

76.74

77.00

77.25

106.78

106.97

109.76

109.81

109.89

113.03

113.25

122.65

124.82

125.24

125.27

125.30

125.33

126.15

127.66

127.75

130.98

134.09

134.35

134.90

134.92

140.05

143.33

157.24

159.13

185.00

S63

1H NMR (500 MHz, CDCl3) spectrum of compound 2o

13C NMR (125 MHz, CDCl3) spectrum of compound 2o

11 10 9 8 7 6 5 4 3 2 1 0 ppm

-0.000

2.612

2.625

2.639

2.652

2.666

4.253

4.267

4.280

4.636

4.649

4.663

7.172

7.173

7.187

7.201

7.203

7.218

7.258

7.327

7.328

7.343

7.345

7.357

7.359

7.378

7.394

7.410

7.627

7.713

7.715

7.717

7.719

7.729

7.731

7.733

7.735

7.746

7.762

8.275

8.291

8.457

8.461

8.464

2.02

2.02

2.00

1.09

1.16

2.09

0.91

2.04

0.97

0.87

200 180 160 140 120 100 80 60 40 20 0 ppm

28.93

40.73

46.66

76.78

77.04

77.24

77.29

109.04

110.04

120.72

122.48

122.52

124.28

124.70

127.54

129.35

129.89

133.61

135.10

135.87

138.22

138.95

143.23

184.57

S64

1H NMR (500 MHz, CDCl3) spectrum of compound 2p

13C NMR (125 MHz, CDCl3) spectrum of compound 2p

9 8 7 6 5 4 3 2 1 0 ppm

-0.000

4.524

4.535

4.547

4.914

4.926

4.937

7.189

7.197

7.205

7.213

7.221

7.230

7.257

7.363

7.370

7.396

7.411

7.427

7.725

7.741

7.760

7.776

8.084

8.351

8.366

8.521

2.02

2.00

1.19

1.97

1.39

2.37

0.99

1.02

0.94

200 180 160 140 120 100 80 60 40 20 0 ppm

39.85

45.38

76.76

77.01

77.27

108.87

109.26

121.24

122.50

122.90

123.44

125.03

128.35

129.29

129.84

133.02

133.47

135.68

137.39

139.24

141.33

184.47

S65

1H NMR (500 MHz, CDCl3 + DMSO-d6) spectrum of compound 2q

13C NMR (125 MHz, CDCl3 + DMSO-d6)) spectrum of compound 2q

10 9 8 7 6 5 4 3 2 1 0 ppm

-0.000

0.922

0.926

0.938

0.945

0.951

1.910

1.923

1.936

1.950

1.963

1.977

2.555

2.558

2.569

2.584

3.141

4.538

4.550

4.562

4.923

4.935

4.947

7.171

7.173

7.185

7.187

7.200

7.203

7.305

7.318

7.322

7.334

7.349

7.362

7.364

7.373

7.389

7.735

7.751

8.011

8.023

8.027

8.034

8.041

8.285

8.289

8.301

8.318

6.17

1.06

2.06

2.00

1.98

1.01

4.41

1.00

0.96

1.95

200 180 160 140 120 100 80 60 40 20 0 ppm

22.44

30.03

39.66

39.83

39.99

40.16

40.33

40.50

40.66

45.34

45.46

78.01

78.27

78.53

107.53

109.92

120.96

122.32

123.85

124.59

128.07

129.03

130.58

132.49

135.26

137.34

141.58

147.27

185.62

S66

1H NMR (500 MHz, CDCl3) spectrum of compound 2r

13C NMR (125 MHz, CDCl3) spectrum of compound 2r

11 10 9 8 7 6 5 4 3 2 1 0 ppm

-0.000

4.527

4.539

4.551

4.917

4.930

4.941

7.189

7.196

7.204

7.212

7.220

7.257

7.353

7.362

7.370

7.458

7.474

7.489

7.569

7.572

7.574

7.576

7.585

7.588

7.590

7.592

7.760

7.776

8.087

8.301

8.303

8.314

8.316

8.373

8.376

8.380

2.14

2.12

1.11

2.07

1.18

1.05

1.07

1.00

1.04

1.00

180 160 140 120 100 80 60 40 20 0 ppm

39.84

45.37

76.76

77.02

77.27

108.85

109.26

121.23

122.88

123.45

125.02

128.35

128.83

129.57

130.59

132.75

133.00

134.49

137.39

139.03

141.36

184.54

S67

1H NMR (500 MHz, DMSO-d6) spectrum of compound 2s

13C NMR (125 MHz, DMSO-d6) spectrum of compound 2s

9 8 7 6 5 4 3 2 1 0 ppm

2.501

2.504

2.508

2.511

2.515

3.323

3.734

3.876

4.652

4.664

4.676

4.975

4.988

5.000

6.654

6.659

6.671

6.675

6.719

6.723

7.145

7.146

7.160

7.175

7.325

7.327

7.342

7.356

7.358

7.486

7.503

7.646

7.662

7.754

7.770

7.794

3.00

3.00

2.03

2.02

1.00

1.01

1.03

1.04

1.01

1.03

1.01

0.94

200 180 160 140 120 100 80 60 40 20 0 ppm

39.56

39.72

39.89

40.06

40.22

40.39

40.48

40.56

45.43

56.04

56.27

99.40

105.58

106.32

110.92

121.06

122.28

122.37

124.29

124.58

127.92

131.07

131.99

137.49

142.33

160.09

163.57

187.19

S68

1H NMR (500 MHz, CDCl3 + DMSO-d6) spectrum of compound 2t

13C NMR (125 MHz, CDCl3 + DMSO-d6) spectrum of compound 2t

9 8 7 6 5 4 3 2 1 0 ppm

-0.000

4.501

4.511

4.524

4.871

4.879

4.889

4.901

7.091

7.107

7.123

7.128

7.135

7.154

7.169

7.184

7.295

7.301

7.313

7.317

7.328

7.349

7.365

7.695

7.715

7.731

7.805

7.824

7.842

7.863

7.985

7.989

8.006

2.00

2.01

2.13

3.28

1.00

2.03

0.99

200 180 160 140 120 100 80 60 40 20 0 ppm

44.38

44.55

44.64

44.71

44.88

45.05

45.21

45.38

50.16

82.81

83.07

83.33

112.24

114.69

121.99

125.04

125.65

126.28

126.98

128.58

129.35

132.79

134.01

137.27

142.07

143.52

146.27

162.22

190.67

S69

1H NMR (500 MHz, CDCl3) spectrum of compound 2u

13C NMR (125 MHz, CDCl3) spectrum of compound 2u

10 9 8 7 6 5 4 3 2 1 0 ppm

-0.000

4.513

4.525

4.538

4.902

4.915

4.927

7.178

7.185

7.186

7.194

7.202

7.210

7.254

7.350

7.358

7.521

7.524

7.536

7.551

7.597

7.600

7.602

7.611

7.614

7.619

7.627

7.629

7.632

7.750

7.766

8.087

8.367

8.370

8.373

8.384

8.386

2.03

2.00

1.08

2.03

2.05

1.08

1.06

0.94

1.94

200 180 160 140 120 100 80 60 40 20 0 ppm

39.86

45.38

76.79

77.05

77.30

108.57

109.26

121.15

122.83

123.63

124.86

128.33

128.36

130.65

132.76

132.92

137.30

137.50

141.75

186.27

S70

1H NMR (500 MHz, DMSO-d6) spectrum of compound 2v

13C NMR (125 MHz, DMSO-d6) spectrum of compound 2v

8 7 6 5 4 3 2 1 0 ppm

0.948

0.963

0.978

1.663

1.677

1.692

1.706

1.721

1.735

2.513

2.525

2.539

3.114

3.128

3.142

3.328

4.296

4.309

4.322

4.587

4.600

4.613

7.123

7.138

7.153

7.288

7.303

7.318

7.424

7.665

7.681

7.710

7.725

3.08

2.10

2.15

2.05

2.00

2.08

0.96

1.01

0.91

2.01

200 180 160 140 120 100 80 60 40 20 0 ppm

14.15

17.55

28.55

39.53

39.70

39.87

40.03

40.20

40.37

40.53

41.26

41.97

47.21

108.80

110.68

120.67

121.91

123.99

125.22

127.12

132.43

138.33

143.33

194.69

S71

1H NMR (500 MHz, DMSO-d6) spectrum of compound 2x

13C NMR (125 MHz, DMSO-d6) spectrum of compound 2x

8 7 6 5 4 3 2 1 0 ppm

0.970

0.984

0.999

1.727

1.742

1.756

1.771

2.509

3.141

3.156

3.170

3.324

4.623

4.635

4.647

4.964

4.976

4.988

7.138

7.152

7.168

7.318

7.333

7.348

7.627

7.644

7.750

7.766

7.839

3.09

2.17

2.12

2.03

2.00

1.09

1.15

1.05

1.05

1.03

200 180 160 140 120 100 80 60 40 20 0 ppm

14.19

17.73

39.52

39.69

39.85

40.02

40.19

40.35

40.52

41.53

45.47

106.66

110.95

121.07

122.41

124.12

124.63

127.87

130.29

137.51

141.43

194.82

S72



9 8 7 6 5 4 3 2 1 0 ppm

2.506

2.509

2.513

2.636

3.351

4.488

4.500

4.513

4.835

4.848

4.860

6.316

6.321

6.323

6.329

7.265

7.268

7.272

7.442

7.445

7.449

7.452

7.571

7.586

7.602

7.665

7.680

7.695

8.215

8.217

8.232

2.02

2.01

1.02

1.04

1.06

2.06

1.06

2.00

200 180 160 140 120 100 80 60 40 20 0 ppm

39.49

39.66

39.83

40.00

40.08

40.16

40.25

40.33

40.42

40.50

43.41

45.34

109.97

114.47

118.54

126.01

128.74

130.53

133.11

133.19

138.01

139.25

185.89

S73

1H NMR (500 MHz, CDCl3) spectrum of compound 4b

13C NMR (125 MHz, CDCl3) spectrum of compound 4b

10 9 8 7 6 5 4 3 2 1 0 ppm

4.397

4.409

4.422

4.776

4.788

4.800

6.370

6.375

6.378

6.383

6.933

6.936

6.938

6.941

7.164

7.170

7.174

7.187

7.201

7.205

7.210

7.222

7.262

7.302

7.640

7.643

7.648

7.650

8.417

8.422

8.427

8.433

8.440

8.447

8.451

8.457

2.08

2.00

1.01

1.00

2.06

0.97

2.00

200 180 160 140 120 100 80 60 40 20 0 ppm

43.58

45.14

76.77

77.02

77.22

77.28

110.82

115.21

115.38

115.63

118.82

124.49

133.19

133.21

133.26

133.93

133.96

139.78

164.58

166.60

184.33

S74



9 8 7 6 5 4 3 2 1 0 ppm

1.995

2.509

3.320

4.506

4.518

4.530

4.860

4.872

4.884

6.345

6.352

6.358

7.301

7.493

7.498

7.888

7.904

7.920

8.516

8.530

8.532

8.645

8.660

9.070

2.04

2.00

1.07

1.06

1.16

1.15

1.05

1.18

0.96

200 180 160 140 120 100 80 60 40 20 0 ppm

39.59

39.76

39.93

40.09

40.26

40.35

40.43

40.52

40.59

43.44

45.42

110.16

114.93

118.38

125.20

126.41

127.40

130.62

133.68

136.55

138.75

139.05

148.12

183.31

S75

1H NMR (500 MHz, CDCl3) spectrum of compound 4d

13C NMR (125 MHz, CDCl3) spectrum of compound 4d

9 8 7 6 5 4 3 2 1 0 ppm

0.000

4.397

4.409

4.422

4.779

4.792

4.804

6.372

6.377

6.379

6.385

6.933

6.936

6.937

6.940

7.261

7.503

7.518

7.533

7.578

7.580

7.593

7.605

7.607

7.651

7.654

7.659

7.662

8.325

8.328

8.342

2.00

2.01

0.95

0.95

1.11

1.03

0.94

1.93

200 180 160 140 120 100 80 60 40 20 0 ppm

43.59

45.14

76.78

77.04

77.24

77.29

110.78

115.50

118.87

124.43

128.22

130.49

132.62

133.10

137.71

139.91

186.22

S76

1H NMR (500 MHz, CDCl3) spectrum of compound 4e

13C NMR (125 MHz, CDCl3) spectrum of compound 4e

9 8 7 6 5 4 3 2 1 0 ppm

2.546

2.559

2.572

2.586

2.600

4.079

4.092

4.106

4.571

4.585

4.598

6.305

6.311

6.318

6.917

6.921

6.925

7.261

7.300

7.302

7.335

7.359

7.375

7.391

7.693

7.694

7.696

7.708

7.710

7.712

8.235

8.251

8.418

2.06

2.00

2.00

1.01

1.05

1.16

1.14

1.13

1.02

0.96

200 180 160 140 120 100 80 60 40 20 0 ppm

29.48

45.12

46.38

76.75

77.00

77.20

77.25

109.28

117.44

118.51

122.40

126.09

129.24

129.75

133.50

135.55

139.30

142.01

184.56

S77

1H NMR (500 MHz, CDCl3) spectrum of compound 4f

13C NMR (125 MHz, CDCl3) spectrum of compound 4f

9 8 7 6 5 4 3 2 1 0 ppm

2.553

2.567

2.580

2.594

2.607

4.089

4.102

4.115

4.577

4.590

4.604

6.320

6.325

6.328

6.333

6.929

6.933

6.934

6.938

7.262

7.295

7.298

7.302

7.306

7.751

7.768

8.378

8.394

2.09

2.05

2.00

0.95

0.98

1.01

2.08

1.94

200 180 160 140 120 100 80 60 40 20 0 ppm

29.47

45.14

46.42

76.75

77.00

77.21

77.26

109.33

117.61

118.45

120.55

122.72

124.89

125.11

125.14

125.17

125.20

126.23

127.05

130.86

133.47

133.72

133.98

134.24

135.71

140.49

141.96

185.01

S78

1H NMR (500 MHz, CDCl3) spectrum of compound 4g

13C NMR (125 MHz, CDCl3) spectrum of compound 4g

9 8 7 6 5 4 3 2 1 0 ppm

2.544

2.557

2.571

2.584

2.598

4.077

4.091

4.104

4.569

4.583

4.596

6.304

6.309

6.311

6.317

6.916

6.920

6.923

7.261

7.420

7.435

7.451

7.539

7.541

7.555

7.557

8.185

8.201

8.267

8.270

8.273

2.04

2.02

2.00

0.94

0.98

1.02

1.02

0.95

0.95

0.91

200 180 160 140 120 100 80 60 40 20 0 ppm

29.48

45.12

46.39

76.76

77.01

77.21

77.26

109.27

117.42

118.51

126.08

128.79

129.48

130.61

132.63

134.39

135.51

139.10

142.04

184.66

S79

1H NMR (500 MHz, CDCl3) spectrum of compound 4h

13C NMR (125 MHz, CDCl3) spectrum of compound 4h

9 8 7 6 5 4 3 2 1 0 ppm

-0.000

2.532

2.545

2.558

2.572

2.585

3.962

3.965

4.067

4.081

4.094

4.562

4.575

4.589

6.283

6.289

6.295

6.896

6.940

6.957

7.215

7.222

7.266

7.870

8.128

8.145

2.07

6.39

2.05

2.00

0.98

0.97

1.11

0.97

0.99

1.00

200 180 160 140 120 100 80 60 40 20 0 ppm

29.51

45.09

46.33

55.99

56.06

76.77

77.03

77.28

109.13

110.07

112.55

116.97

118.80

125.64

126.23

130.36

134.97

142.83

148.80

153.35

184.49

catalyst-free facile synthesis of polycyclic indole ... · s1 catalyst-free facile synthesis of...

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