Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1]O.[CH3:3][S:4][C:5]1[NH:6][CH:7]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=2)[N:9]=1>CO>[CH3:3][S:4]([C:5]1[NH:6][CH:7]=[C:8]([C:10]2[CH:11]=[CH:12][C:13]([N+:16]([O-:18])=[O:17])=[CH:14][CH:15]=2)[N:9]=1)=[O:1]
Reactant: CSc1nc(-c2ccc([N+](=O)[O-])cc2)c[nH]1
Reactant: OO
Solvent: CO
Product: CS(=O)c1nc(-c2ccc([N+](=O)[O-])cc2)c[nH]1
Temperature: 60 °C

Procedure:
Hydrogen peroxide (36%, 100 ml) was added over a period of 2 hours, while stirring, to a hot (60° C.) solution of 2-methylthio-4-(4-nitro-phenyl)-1H-imidazole (19.6 g) in methanol (500 ml). After an additional 24 hours of heating at 60° C., the mixture was cooled to room temperature, filtered, and the filter cake was dried to give 16.1 g of the title compound.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4]([NH:27][NH:28][C:29]([C:31]2[O:32][CH:33]=[CH:34][CH:35]=2)=O)[C:5]2[CH:10]=[CH:9][N:8]([CH2:11][CH2:12][N:13]([CH2:15][CH2:16][N:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])[CH3:18])[CH3:14])[C:6]=2[N:7]=1>C[Si](N[Si](C)(C)C)(C)C>[NH2:1][C:2]1[N:27]2[N:28]=[C:29]([C:31]3[O:32][CH:33]=[CH:34][CH:35]=3)[N:3]=[C:4]2[C:5]2[CH:10]=[CH:9][N:8]([CH2:11][CH2:12][N:13]([CH3:14])[CH2:15][CH2:16][N:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])[CH3:18])[C:6]=2[N:7]=1
Reactant: CN(CCN(C)c1ccc(F)cc1F)CCn1ccc2c(NNC(=O)c3ccco3)nc(N)nc21
Agent: C[Si](C)(C)N[Si](C)(C)C
Product: CN(CCN(C)c1ccc(F)cc1F)CCn1ccc2c1nc(N)n1nc(-c3ccco3)nc21
Temperature: 120 °C
Reaction time: 1 h

Procedure:
The title C compound, N′-(2-amino-7-(2-((2-((2,4-difluorophenyl)(methyl)amino)ethyl)-(methyl)amino)ethyl) -7H-pyrrolo[2,3-d]pyrimidin-4-yl)furan-2-carbohydrazide (crude from the previous step) (0.50 mmol) is dissolved in 2 mL of HMDS and 2 mL of BSA. The mixture is heated at 120° C. overnight, then cooled down to RT and the solvent removed in vacuo. The residue is dissolved in a mixture of DCM (2 mL) and 6N aqueous HCl (2 mL), and stirred at RT for 1 h. The pH value is adjusted to 12 using 1M aqueous NaOH. The organic phase is separated and the aqueous phase is extracted with additional DCM. The combined organic phase is dried over anhydrous Na2SO4, filtered and evaporated. The residue is purified by flash chromatography to obtain N1-(2-(5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)ethyl)-N2-(2,4-difluorophenyl)-N1,N2-dimethylethane-1,2-diamine: LC/MS (M+1=467). 1H NMR (DMSO-d6) δ 2.22 (s, 3H), 2.42-2.49 (m, 2H), 2.65 (s, 3H), 2.72 (t, 2H, J=6.37 Hz), 3.01 (t, 2H, J=6.81 Hz), 4.16 (t, 2H, J=6.37 Hz), 6.57 (d, 1H, J=3.42 Hz), 6.70 (dd, 1H, J=3.39 Hz and 1.78 Hz), 6.75-6.90 (m, 2H), 7.01-7.16 (m, 2H), 7.18 (dd, 1H, J=3.39 Hz and 0.81 Hz), 7.47 (s, 2H), 7.99 (dd, 1H, J=1.73 Hz and 0.81 Hz).
Reaction SMILES: [CH3:1][Si:2]([CH3:12])([CH3:11])[C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1.Cl.[F:14][C:15]([F:27])([F:26])[O:16][C:17]1[CH:18]=[C:19]([CH2:23][CH2:24][NH2:25])[CH:20]=[CH:21][CH:22]=1.C(N(CC)CC)C.[BH4-].[Na+]>CO.O>[F:14][C:15]([F:26])([F:27])[O:16][C:17]1[CH:18]=[C:19]([CH2:23][CH2:24][NH:25][CH2:7][C:6]2[CH:9]=[CH:10][C:3]([Si:2]([CH3:12])([CH3:11])[CH3:1])=[CH:4][CH:5]=2)[CH:20]=[CH:21][CH:22]=1
Reactant: C[Si](C)(C)c1ccc(C=O)cc1
Reactant: NCCc1cccc(OC(F)(F)F)c1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CO
Solvent: O
Product: C[Si](C)(C)c1ccc(CNCCc2cccc(OC(F)(F)F)c2)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 100.7 %

Procedure:
4-Trimethylsilanyl-benzaldehyde (178 mg, 1 mmol), 2-(3-trifluoromethoxy-phenyl)-ethyl-amine hydrochloride (241 mg, 1.1 mmol) and triethyl amine (151 mg, 1.5 mmol) were dissolved in methanol (5 ml) and the solution was stirred at rt for 5 min. Sodium borohydride (37 mg, 1 mmol) was added under nitrogen and the reaction mixture was stirred at rt for 1 h. Water was added and methanol was evaporated in vacuo. The reaction was extracted twice with diethyl ether and the combined organic layers were washed once with water and once with sat. aq. NaCl solution, dried with sodium sulfate, filtered off and concentrated in vacuo to yield [2-(3-trifluoromethoxy-phenyl)-ethyl]-(4-trimethylsilanyl-benzyl)-amine (370 mg, 100%) as a colorless oil. MS (ISP) 368.2 (100) (M+H)+.
Reaction SMILES: [BH4-].[Na+].[Cl:3][C:4]1[N:9]=[CH:8][C:7]([C:10](=[N:12]O)[CH3:11])=[CH:6][CH:5]=1.[OH-].[NH4+]>COCCOC.[Ti](Cl)(Cl)(Cl)Cl>[Cl:3][C:4]1[N:9]=[CH:8][C:7]([CH:10]([NH2:12])[CH3:11])=[CH:6][CH:5]=1
Reactant: CC(=NO)c1ccc(Cl)nc1
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: [BH4-]
Agent: [NH4+]
Solvent: COCCOC
Product: CC(N)c1ccc(Cl)nc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 38.3 %

Procedure:
Cool a solution of sodium borohydride (2.96 g, 82.65 mmol) and titanium tetrachloride (1 M in toluene, 41.33 mL, 41.33 mmol) in 50 mL of dry 1,2-dimethoxyethane to 0° C. under N2. Add 1-(6-chloropyridin-3-yl)ethanone oxime (3.52 g, 20.66 mmol) to the solution dropwise. Stir the mixture overnight at RT. Quench the reaction with 200 mL of water. Basify the mixture with ammonium hydroxide. Subsequently, extract the crude product into toluene and ethyl acetate. Separate the layers and dry the organic layer over sodium sulfate. Concentrate in vacuo to give the crude product (1.24 g, 38%). 1H NMR (400 MHz, CDCl3) δ 3.53 (s, 3H), 5.23 (s, 2H), 7.39 (d, J=4.0 Hz, 1H), 7.96 (d, J=1.6 Hz, 1H).
Reaction SMILES: [Cl:1][C:2]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:9]2[C:4](=[CH:5][C:6]([C:18]3[O:22][C:21]([CH:23]=[O:24])=[CH:20][CH:19]=3)=[CH:7][CH:8]=2)[N:3]=1.[CH3:25][Mg]Br.C(OCC)C>C1COCC1>[Cl:1][C:2]1[N:11]=[C:10]([N:12]2[CH2:13][CH2:14][O:15][CH2:16][CH2:17]2)[C:9]2[C:4](=[CH:5][C:6]([C:18]3[O:22][C:21]([CH:23]([OH:24])[CH3:25])=[CH:20][CH:19]=3)=[CH:7][CH:8]=2)[N:3]=1
Reactant: O=Cc1ccc(-c2ccc3c(N4CCOCC4)nc(Cl)nc3c2)o1
Reactant: C[Mg]Br
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC(O)c1ccc(-c2ccc3c(N4CCOCC4)nc(Cl)nc3c2)o1
Temperature: 0 °C
Reaction time: 3 h

Procedure:
To a 50 mL round bottom flask, 5-(2-chloro-4-morpholino-quinazolin-7-yl)furan-2-carbaldehyde (0.5 g, 0.001457 mol) and THF (25 mL) was added and cooled to 0° C. To the flask was slowly added 1.5 M methyl magnesium bromide in diethyl ether (0.145 mL, 0.002186 mol). The resulting reaction mixture was stirred at room temperature for 3 h. The reaction was quenched with water and extracted with ethyl acetate (3×50 mL). The organic layer was dried over anhydrous sodium sulfate and evaporated to provide the crude product. The crude product was purified by column chromatography using 60-120 silica gel and 40% ethyl acetate in hexane [0.3 g, 57%]. 1H NMR (300 MHz, CDCl3): δ 8.05 (d, J=1.2 Hz, 1H), 7.83 (d, J=6.3 Hz, 1H), 7.71 (dd, J′=6.6, J″=1.2 Hz, 1H), 6.82 (d, J=2.4 Hz, 1H), 6.40 (d, J=2.7 Hz, 1H), 4.91 (q, J=4.8 Hz, 1H), 3.89 (s, 8H), 1.63 (d, J=4.8 Hz, 3H). LC-MS (ESI): Calculated mass: 359.1; Observed mass: 360.1 (RT: 1.58 min).
Reaction SMILES: [CH3:1][CH:2]1[CH:6]([C:7]([O:9][CH2:10][O:11][C:12](=[O:17])[C:13]([CH3:16])([CH3:15])[CH3:14])=[O:8])[N:5]2[C:18](=[O:43])[CH:19]([NH:20][C:21](=[O:42])[CH:22]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[NH:23][C:24]([N:26]3[CH2:31][CH2:30][N:29]([CH2:32][CH3:33])[C:28](=[O:34])[C:27]3=[O:35])=[O:25])[C@H:4]2[C:3]1=[O:44].C(Cl)Cl.[BH4-].C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)(=O)C.C(Cl)(Cl)Cl>[OH:44][CH:3]1[C@@H:4]2[CH:19]([NH:20][C:21](=[O:42])[CH:22]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[NH:23][C:24]([N:26]3[CH2:31][CH2:30][N:29]([CH2:32][CH3:33])[C:28](=[O:34])[C:27]3=[O:35])=[O:25])[C:18](=[O:43])[N:5]2[CH:6]([C:7]([O:9][CH2:10][O:11][C:12](=[O:17])[C:13]([CH3:16])([CH3:15])[CH3:14])=[O:8])[CH:2]1[CH3:1]
Reactant: CCN1CCN(C(=O)NC(C(=O)NC2C(=O)N3C(C(=O)OCOC(=O)C(C)(C)C)C(C)C(=O)[C@H]23)c2ccccc2)C(=O)C1=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [BH4-]
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Solvent: CCOC(C)=O
Product: CCN1CCN(C(=O)NC(C(=O)NC2C(=O)N3C(C(=O)OCOC(=O)C(C)(C)C)C(C)C(O)[C@H]23)c2ccccc2)C(=O)C1=O
Yield: 15.2 %

Procedure:
Pivaloyloxymethyl 2-methyl-1-oxo-6-[2-phenyl-2-(4-ethyl-2,3dioxopiperazine-1-carboxamido)acetamido]carbapenam-3-carboxylate (103 mg., 0.16 mmole) in 10 ml. of methylene chloride was reacted with tetrabutylammonium borohydride (11 mg., 0.04 mmole) at -78° C. After 15 minutes tlc (ethyl acetate) indicated reduction was complete. Isolation according to Example 3, except using 1:1 chloroform:ethyl acetate as eluant in the chromatography, afforded pivaloyloxymethyl 1-hydroxy-2-methyl-6-[2-phenyl-2-(4-ethyl-2,3-dioxopiperazine-1-carboxamido)acetamido]carbapenam-3-carboxylate [15 mg., 15%; ir (CH2Cl2) 1775, 1760, 1720, 1690 cm-1 ; Rf 0.0 (ethyl acetate)].
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][S:5][C:6]=1[CH2:7][CH2:8]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:29]N1C(=O)CCC1=O>ClCCl>[Br:29][CH2:8][CH2:7][C:6]1[S:5][CH:4]=[N:3][C:2]=1[CH3:1]
Reactant: Cc1ncsc1CCO
Reactant: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: Cc1ncsc1CCBr
Temperature: 0 °C
Reaction time: 2 h
Yield: 62.6 %

Procedure:
1 g (6.98 mmol) of 2-(4-methylthiazol-5-yl)ethanol is dissolved in 15 mL of dichloromethane. The solution is cooled to 0° C. When the temperature is reached, 1.85 g (6.98 mmol) of triphenylphosphine are added, followed by portionwise addition of 1.30 g (6.98 mmol) of N-bromosuccinimide. After stirring for 2 hours at 0° C., the mixture is evaporated to dryness. The residue is purified by chromatography on silica gel (eluent: 50/50 EtOAc/heptane) to give 900 mg of 5-(2-bromoethyl)-4-methylthiazole, the characteristics of which are as follows:
Reaction SMILES: FC1C=C(C[C@H](NC(=O)CN2C3CCCCC=3C(C(F)(F)F)=N2)C2N(C3C=CC(OC)=CC=3)C=CN=2)C=C(F)C=1.Cl.[Cl:42][C:43]1[CH:48]=[CH:47][C:46]([C:49]2[O:50][C:51]([CH:54]([NH2:64])[CH2:55][C:56]3[CH:61]=[C:60]([F:62])[CH:59]=[C:58]([F:63])[CH:57]=3)=[CH:52][N:53]=2)=[CH:45][CH:44]=1.[OH:65][C:66]1[CH:67]=[C:68]2[C:72](=[CH:73][CH:74]=1)[NH:71][CH:70]=[C:69]2[CH2:75][C:76](O)=[O:77]>>[Cl:42][C:43]1[CH:48]=[CH:47][C:46]([C:49]2[O:50][C:51]([CH:54]([NH:64][C:76](=[O:77])[CH2:75][C:69]3[C:68]4[C:72](=[CH:73][CH:74]=[C:66]([OH:65])[CH:67]=4)[NH:71][CH:70]=3)[CH2:55][C:56]3[CH:61]=[C:60]([F:62])[CH:59]=[C:58]([F:63])[CH:57]=3)=[CH:52][N:53]=2)=[CH:45][CH:44]=1
Reactant: NC(Cc1cc(F)cc(F)c1)c1cnc(-c2ccc(Cl)cc2)o1
Reactant: O=C(O)Cc1c[nH]c2ccc(O)cc12
Agent: COc1ccc(-n2ccnc2[C@H](Cc2cc(F)cc(F)c2)NC(=O)Cn2nc(C(F)(F)F)c3c2CCCC3)cc1
Agent: Cl
Product: O=C(Cc1c[nH]c2ccc(O)cc12)NC(Cc1cc(F)cc(F)c1)c1cnc(-c2ccc(Cl)cc2)o1

Procedure:
The title compound was prepared according to the method presented for the synthesis of compound 5F of Example 5 utilizing 19E and 2-(5-hydroxy-1H-indol-3-yl)acetic acid. 1H NMR (400 MHz, CDCl3) δ 8.06 (s, 1H), 7.81 (d, J=8.3 Hz, 2H), 7.41 (d, J=8.5 Hz, 2H), 7.27 (m, 1H), 7.08 (s, 1H), 6.87-6.76 (m, 2H), 6.60 (m, 1H), 6.47 (d, J=6.0 Hz, 2H), 6.30 (s, 1H), 5.26 (d, J=7.9 Hz, 1H), 3.67 (s, 2H), 3.08-2.93 (m, 2H). MS (m/z) 508.1 [M+H]+.
Reaction SMILES: [OH-].[Na+].[NH2:3][C:4]([CH3:15])([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([I:14])[CH:9]=1)[CH2:5][OH:6].[Cl:16][CH2:17][C:18](Cl)=[O:19]>C(Cl)Cl>[Cl:16][CH2:17][C:18]([NH:3][C:4]([CH2:5][OH:6])([CH3:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([I:14])[CH:9]=1)=[O:19]
Reactant: O=C(Cl)CCl
Reactant: CC(N)(CO)Cc1cccc(I)c1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CC(CO)(Cc1cccc(I)c1)NC(=O)CCl
Temperature: 35 °C

Procedure:
NaOH 1M aq. soln. (10 mL) followed by NaOH 32% (270 μL) were added to a 0° C. solution of rac-2-amino-3-(3-iodo-phenyl)-2-methyl-propan-1-ol H-6 (850 mg, 2.92 mmol) in DCM (10 mL). After 10 min a solution of chloroacetyl chloride (261 mL, 3.21 mmol) in DCM (10 mL) was added dropwise to the reaction mixture maintaining the temperature below 5° C. The resulting suspension was heated to 35° C. for 30 min after which complete formation of product was observed by LCMS. The layers were separated and the aqueous layer extracted with DCM (2×). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and evaporated in vacuo to give the title compound that was used further without purification. LC-MS A: tR=0.79 min; [M(35Cl)+H]+=367.91.
Reaction SMILES: [NH2:1][C:2]([C:4]1([NH:9][C:10](=O)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])[CH2:8][CH2:7][CH2:6][CH2:5]1)=[O:3].[OH-].[Na+].Cl>CO.C(Cl)Cl>[Cl:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:10]1[NH:1][C:2](=[O:3])[C:4]2([CH2:8][CH2:7][CH2:6][CH2:5]2)[N:9]=1
Reactant: NC(=O)C1(NC(=O)c2ccccc2Cl)CCCC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: ClCCl
Product: O=C1NC(c2ccccc2Cl)=NC12CCCC2
Temperature: 90 °C

Procedure:
Into a solution of N-[1-(aminocarbonyl)cyclopentyl]-2-chlorobenzamide from Step A (0.51 g, 1.912 mmol) in methanol (10 mL) was added NaOH (1.15 mL, 5 N). This solution was heated at 90° C. for 2.5 h. After allowing the reaction mixture to cool, the bulk of the solvent was removed in vacuo to give a residue, which was then neutralized by the addition of 1 N HCl and diluted with DCM. The layers were separated and the aqueous layer was extracted with an additional volume of DCM. The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo to yield the title compound as a white solid. MS: m/z=249 (M+1).
Reaction SMILES: O=C1CCC(=O)N1O[C:9](=[O:27])[C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17](=[O:26])[N:18]([CH3:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:12][CH:11]=1.[CH3:28][C:29]([CH3:34])([CH3:33])[CH2:30][CH2:31][NH2:32]>>[CH3:28][C:29]([CH3:34])([CH3:33])[CH2:30][CH2:31][NH:32][C:9]([C:10]1[CH:11]=[CH:12][C:13]([O:16][C:17](=[O:26])[N:18]([CH3:25])[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:14][CH:15]=1)=[O:27]
Reactant: CN(C(=O)Oc1ccc(C(=O)ON2C(=O)CCC2=O)cc1)c1ccccc1
Reactant: CC(C)(C)CCN
Product: CN(C(=O)Oc1ccc(C(=O)NCCC(C)(C)C)cc1)c1ccccc1

Procedure:
The title product was prepared from 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester and 3,3-dimethylbutylamine. The crude product was used without further purification (88%, oil). HPLC-MS: m/z=355.1 (M+1); Rt: 3.10 min.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([C:12]1[CH:13]=[C:14]([CH:25]=[CH:26][CH:27]=1)[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])[C:6]([CH3:29])([CH3:28])[CH:5]2O.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([C:12]1[CH:13]=[C:14]([CH:25]=[CH:26][CH:27]=1)[C:15]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:16])[C:6]([CH3:29])([CH3:28])[CH2:5]2
Reactant: CC1(C)C(O)c2cc(Cl)ccc2NC1c1cccc(C(=O)OCc2ccccc2)c1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC1(C)Cc2cc(Cl)ccc2NC1c1cccc(C(=O)OCc2ccccc2)c1
Temperature: 25 °C
Yield: 47.9 %

Procedure:
To a sealed tube was added benzyl 3-(6-chloro-4-hydroxy-3,3-dimethyl-1,2,3,4-tetrahydroquinolin-2-yl)benzoate (1.98 g, 4.70 mmol), dichloromethane (25 ml) and triethylsilane (1.10 g, 9.40 mmol, 2.0 eq.), followed by the addition of trifluoroacetic acid (1.61 g, 14.11 mmol, 3.0 eq.). The sealed tube was heated at 60 for 16 h and cooled to room temperature. The reaction mixture was washed with saturated Sodium bicarbonate and separated. The organic layer was dried the residue was purified by column chromatography using petroleum ether/ethyl acetate=20:1 to afford benzyl 3-(6-chloro-3,3-dimethyl-1,2,3,4-tetrahydroquinolin-2-yl)benzoate 914 mg (47.9% yield) as a yellow solid. MS (ESI+APCI) M+1=406.2.
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.COC1C=C(OC)C=CC=1C[N:17]([CH2:32][C:33]1[CH:38]=[CH:37][N:36]=[C:35]2[NH:39][C:40]([C:42]3[C:50]4[C:45](=[CH:46][C:47]([O:53][CH3:54])=[C:48]([O:51][CH3:52])[CH:49]=4)[N:44]([CH3:55])[CH:43]=3)=[CH:41][C:34]=12)[S:18]([C:21]1[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=1)(=[O:20])=[O:19].[OH-].[Na+]>ClCCl.C1(C)C=CC=CC=1.O>[CH3:52][O:51][C:48]1[CH:49]=[C:50]2[C:45](=[CH:46][C:47]=1[O:53][CH3:54])[N:44]([CH3:55])[CH:43]=[C:42]2[C:40]1[NH:39][C:35]2=[N:36][CH:37]=[CH:38][C:33]([CH2:32][NH:17][S:18]([C:21]3[CH:22]=[CH:23][C:24]([O:27][C:28]([F:29])([F:30])[F:31])=[CH:25][CH:26]=3)(=[O:19])=[O:20])=[C:34]2[CH:41]=1
Reactant: COc1ccc(CN(Cc2ccnc3[nH]c(-c4cn(C)c5cc(OC)c(OC)cc45)cc23)S(=O)(=O)c2ccc(OC(F)(F)F)cc2)c(OC)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: O
Solvent: ClCCl
Product: COc1cc2c(-c3cc4c(CNS(=O)(=O)c5ccc(OC(F)(F)F)cc5)ccnc4[nH]3)cn(C)c2cc1OC
Temperature: 25 °C
Reaction time: 24 h
Yield: 20.3 %

Procedure:
0.053 g of para-toluenesulfonic acid is added to a solution of 0.050 g of N-(2,4-dimethoxybenzyl)-N-[2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl]-4-trifluoromethoxybenzenesulfonamide in 2 cm3 of dichloromethane and 5 cm3 of toluene, at a temperature in the region of 20° C. The reaction medium is stirred at this same temperature for 24 hours, at room temperature, and then heated at a temperature in the region of 60° C. for 24 hours. After cooling, the reaction medium is concentrated under reduced pressure. 5 cm3 of water and 10 cm3 of dichloromethane are added. The reaction medium is basified to pH 9 with 1N sodium hydroxide. After separation of the phases by settling, the organic phase is dried over magnesium sulfate, filtered and then concentrated under reduced pressure. The residue obtained is purified on preparative LC/MS (water/acetonitrile/TFA). The solid obtained is taken up in 5 cm3 of dichloromethane and 2 cm3 of water, and then basified with 1N sodium hydroxide to pH 9. 0.008 g of N-[2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl]-4-trifluoromethoxybenzenesulfonamide is obtained, the characteristics of which are as follows:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:35][CH3:36])=[C:6]([CH:34]=1)[CH2:7][CH:8]1[C:14](=[O:15])[N:13]([C:16]([NH:18][CH:19]([CH2:31][CH3:32])[C:20]([NH:22][CH2:23][C:24](OC(C)(C)C)=O)=[O:21])=[O:17])[CH2:12][C:11](=[O:33])[NH:10][CH2:9]1.Cl.C(OC(=O)CN)(C)(C)C.C(OC([C:54]1(N)C=C[CH:57]=[C:56]([NH2:60])[CH2:55]1)=O)(C)(C)C>>[NH2:60][C:56]1[CH:57]=[C:23]([CH:24]=[CH:54][CH:55]=1)[NH:22][C:20]([C@H:19]([NH:18][C:16]([N:13]1[C:14](=[O:15])[CH:8]([CH2:7][C:6]2[CH:34]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[O:35][CH3:36])[CH2:9][NH:10][C:11](=[O:33])[CH2:12]1)=[O:17])[CH2:31][CH3:32])=[O:21]
Reactant: CC(C)(C)OC(=O)C1(N)C=CC=C(N)C1
Reactant: CCC(NC(=O)N1CC(=O)NCC(Cc2cc(Cl)ccc2OC)C1=O)C(=O)NCC(=O)OC(C)(C)C
Agent: CC(C)(C)OC(=O)CN
Agent: Cl
Product: CC[C@@H](NC(=O)N1CC(=O)NCC(Cc2cc(Cl)ccc2OC)C1=O)C(=O)Nc1cccc(N)c1

Procedure:
Instead of the starting material compound of Example 220, that is, the glycine tert-butyl ester hydrochloride, 1-(tert-butoxycarbonyl)-1,3-phenylenediamine was used for the similar procedure as in Example 220 and Example 245 to obtain the title compound.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:31])[C:4]1[CH:9]=[C:8](Br)[CH:7]=[C:6]([CH3:11])[C:5]=1[N:12]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[S:13]([C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)(=[O:15])=[O:14].C[Si]([C:36]#[CH:37])(C)C>CN(C=O)C.C(N(CC)CC)C.CCOCC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[CH3:1][O:2][C:3](=[O:31])[C:4]1[CH:9]=[C:8]([C:36]#[CH:37])[CH:7]=[C:6]([CH3:11])[C:5]=1[N:12]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[S:13]([C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)(=[O:15])=[O:14]
Reactant: COC(=O)c1cc(Br)cc(C)c1N(Cc1ccccc1)S(=O)(=O)c1ccc(OC)cc1
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOCC
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: C#Cc1cc(C)c(N(Cc2ccccc2)S(=O)(=O)c2ccc(OC)cc2)c(C(=O)OC)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 80 %

Procedure:
To a solution of 0.277 g (0.50 mmol) of the product of Example 11 in 2.0 mL of DMF and 2.0 mL of triethylamine was added 0.39 mL (0.2.748 mmol) of trimetylsilyl acetylene, 19 mg (0.027 mmol) of bis(triphenylphosphine)palladium(II)dichloride and 2.6 mg of copper(I)iodide. The reaction mixture was then heated to 65 degrees for 2 h and then cooled to room temperature and diluted with ether. The organics were washed with 5% Hcl solution, water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was dissolved in 5 mL of THF, 1 mL of 1M tetrbutylammonium fluoride-THF solution was added and the reaction was stirred at room temperatue for 1 h, then diluted with ether, washed with 5% HCl solution, water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was chromatographed on silica eluting with EtOAc-Hex (1:10) to provide 0.197 g (80%) of the desired product as a white foam. Electrospray Mass Spec: 450.3 (M+H)+.
Reaction SMILES: C(OC([N:8]1[CH2:24][CH2:23][C:11]2[NH:12][C:13]3[C:14]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:16]=[CH:17][C:18]=3[C:10]=2[CH2:9]1)=O)(C)(C)C.Cl>C(Cl)Cl.O1CCOCC1>[CH3:22][S:19]([C:14]1[C:13]2[NH:12][C:11]3[CH2:23][CH2:24][NH:8][CH2:9][C:10]=3[C:18]=2[CH:17]=[CH:16][CH:15]=1)(=[O:20])=[O:21]
Reactant: CC(C)(C)OC(=O)N1CCc2[nH]c3c(S(C)(=O)=O)cccc3c2C1
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: CS(=O)(=O)c1cccc2c3c([nH]c12)CCNC3
Reaction time: 2.5 h

Procedure:
6-methanesulfonyl-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester (214 mg, 0.61 mmol) was dissolved in DCM (1 mL) and the 4M HCl in dioxane (1 mL) added. Evolution of gas commenced immediately and the reaction was stirred for 2.5 h when no further evolution was observed but a black solid had separated from the reaction.
Reaction SMILES: [CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].[CH2:7]([NH:9][C:10](=[O:20])[CH:11]([C:13]1[CH:18]=[CH:17][C:16](I)=[CH:15][CH:14]=1)[CH3:12])[CH3:8].CCOC(C)=O>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH2:7]([NH:9][C:10](=[O:20])[CH:11]([C:13]1[CH:18]=[CH:17][C:16]([C:6]#[C:5][Si:2]([CH3:4])([CH3:3])[CH3:1])=[CH:15][CH:14]=1)[CH3:12])[CH3:8]
Reactant: CCNC(=O)C(C)c1ccc(I)cc1
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CCNC(=O)C(C)c1ccc(C#C[Si](C)(C)C)cc1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
To 4.90 g (49.9 mmol) trimethylsilylacetylene in 450 mL acetonitrile are added 12.1 g (39.9 mmol) N-ethyl-2-(4-iodo-phenyl)-propionamide (IV.1) under argon, followed by 1.68 g (2.40 mmol) Pd(PPh3)2Cl2 as catalyst, 0.23 g (1.20 mmol) copper(I)iodide and 11.1 mL (80 mmol) TEA as base. The mixture is stirred at rt for 2.5 h. After that time, EtOAc is added and the organic layer is washed with saturated ammonium chloride solution and brine. The organic layer is separated, dried over sodium sulphate and the solvent is evaporated. The residue is purified by column chromatography (silicia gel; EtOAc/heptane, gradient 50% to 80%) to yield the desired product.