Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:30]#[N:31])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([O:27][CH3:28])[CH2:23][CH2:22]3)[C:17](O)=[O:18])[C:10](=[O:29])[CH:9]=2)[CH:7]=1.[NH2:32][C:33]1[CH:43]=[CH:42][C:36]([C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:35][CH:34]=1.CC(C)N=C=NC(C)C>CN(C)C=O.[Cl-].[Li+].C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:30]#[N:31])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([O:27][CH3:28])[CH2:23][CH2:22]3)[C:17]([NH:32][C:33]3[CH:34]=[CH:35][C:36]([C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:42][CH:43]=3)=[O:18])[C:10](=[O:29])[CH:9]=2)[CH:7]=1
Reactant: CCOC(=O)c1ccc(N)cc1
Reactant: COc1cn(C(C[C@H]2CC[C@H](OC)CC2)C(=O)O)c(=O)cc1-c1cc(Cl)ccc1C#N
Agent: CC(C)N=C=NC(C)C
Agent: [Cl-]
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)c1ccc(NC(=O)C(C[C@H]2CC[C@H](OC)CC2)n2cc(OC)c(-c3cc(Cl)ccc3C#N)cc2=O)cc1

Procedure:
1.70 g (purity 82%, 3.82 mmol) of 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-(trans-4-methoxycyclohexyl)propanoic acid (racemate), 631 mg (3.82 mmol) of ethyl 4-aminobenzoate, 543 mg (3.82 mmol) of Oxima and 595 μl (3.82 mmol) of DIC in 38 ml of dimethylformamide were reacted according to General Method 5B. After complete conversion, the reaction solution was diluted with 213 ml of 10% strength lithium chloride solution and 170 ml of ethyl acetate and the phases were separated. The aqueous phase was extracted twice with 170 ml of ethyl acetate. The combined organic phases were dried over magnesium sulphate and filtered, and the solvent was removed under reduced pressure. The crude product was purified by column chromatography (ethyl acetate/cyclohexane gradient, 100 g silica cartridge, flow rate 50 ml/min), giving the title compound. Yield: 1.1 g (purity 78%, 49% of theory)
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][CH:7]=1.C(N(CC)CC)C.Cl[C:22](Cl)([O:24]C(=O)OC(Cl)(Cl)Cl)Cl>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:13])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]=[C:22]=[O:24])=[CH:8][CH:7]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COC(=O)COc1ccc(N)cc1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: COC(=O)COc1ccc(N=C=O)cc1
Temperature: 25 °C
Yield: 159.1 %

Procedure:
To a mixture of (4-Amino-phenoxy)-acetic acid methyl ester 15 (15 g, 82.87 mmol) and triethylamine (16.77 g, 165.73 mmol) in toluene (225 ml) under nitrogen atm. at 0° C. was added triphosgene (9 g, 30.33 mmol) in one lot. The reaction was exothermic and the temperature raised to 25° C. Later the reaction mixture was heated to 75° C. over a period of one hour and maintained at this temperature for 26 hours. The reaction mixture was then cooled to room temperature, the solids were filtered off, and the toluene was distilled off under vacuum to get crude 28, which was vacuum distilled to get pure 28 (10 g, 58.3%) as a white powder. M.p: 50-53° C.
Reaction SMILES: [F:1][C:2]1[C:11]2[C:12]3[CH:13]=[CH:14][C:15]([F:20])=[CH:16][C:17]=3[C:18](=O)[C:10]=2[CH:9]=[C:8]2[C:3]=1C(C)=CC(C)(C)[NH:7]2.CCCCCC.CC[O:32]C(C)=O>>[NH2:7][C:8]1[C:9](=[O:32])[C:10]2[C:11](=[C:2]([F:1])[CH:3]=1)[C:12]1[C:17](=[CH:16][C:15]([F:20])=[CH:14][CH:13]=1)[CH:18]=2
Reactant: CCOC(C)=O
Reactant: CC1=CC(C)(C)Nc2cc3c(c(F)c21)-c1ccc(F)cc1C3=O
Solvent: CCCCCC
Product: NC1=CC(F)=C2C(=Cc3cc(F)ccc32)C1=O

Procedure:
This compound was prepared according to General Method 3 (EXAMPLE 16) from Compound 132 (1.0 g, 4.6 mmol) to afford 5,8-difluoro-1,2-dihydro-2,2,4-trimethyl-10-oxoindeno[1,2-g]quinoline (structure 19 of Scheme VI, where R2, R5 =F, R3-4, R6 =H). Data for 5,8-difluoro-1,2-dihydro-2,2,4-trimethyl-10-oxoindeno[1,2-g]quinoline: Rf =0.49 (silca gel, hexane/EtOAc, 3:1), 1H NMR (400 MHz, acetone-d6) 7.50 (dd, J=8.1, 4.6, 1H), 7.27 (m, 2H), 6.73 (s, 1H), 6.03 (br s, 1H), 5.47 (s, 1H), 2.16 (dd, J=7.1, 1.5, 3H), 1.29 (s, 6H).
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]([CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][S:17][C:16]2[CH:20]=[CH:21][C:22]([N+:24]([O-])=O)=[CH:23][C:15]1=2)[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].I.[S:28]1[CH:32]=[CH:31][CH:30]=[C:29]1[C:33](SC)=[NH:34]>C(O)C.ClCCl.[Pd]>[OH:1][CH2:2][CH2:3][N:4]([CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][S:17][C:16]2[CH:20]=[CH:21][C:22]([NH:24][C:33]([C:29]3[S:28][CH:32]=[CH:31][CH:30]=3)=[NH:34])=[CH:23][C:15]1=2)[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(C)OC(=O)N(CCO)CCN1CCSc2ccc([N+](=O)[O-])cc21
Reactant: CSC(=N)c1cccs1
Agent: [Pd]
Agent: I
Solvent: ClCCl
Solvent: CCO
Product: CC(C)(C)OC(=O)N(CCO)CCN1CCSc2ccc(NC(=N)c3cccs3)cc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 47.6 %

Procedure:
A stirred suspension of tert-butyl 2-hydroxyethyl(2-(6-nitro-2H-benzo[b][1,4]thiazin-4(3H)-yl)ethyl)carbamate (590 mg, 1.539 mmol) and palladium, 10 wt. % on activated carbon (164 mg, 0.154 mmol) in ethanol (10 mL) was stirred at room temperature under an atmosphere of hydrogen (1 atm) for 2 hours (yellow color disappears). To this mixture was then added methyl thiophene-2-carbimidothioate hydroiodide (878 mg, 3.08 mmol), and the resulting mixture was stirred overnight at room temperature. The mixture was then diluted with dichloromethane and then filtered through Celite. The filtrate was then diluted with water and extracted with dichloromethane (4×). The combined organics were dried, filtered, concentrated, and then chromatographed in ethyl acetate, giving the desired product (339 mg, 47.6%) as a yellow foam. 1H NMR (DMSO-d6) δ 7.69 (s, 1H), 7.58 (d, J=4.8 Hz, 1H), 7.07 (t, J=4.2 Hz, 1H), 6.41-6.25 (m, 3H), 6.08 (d, J=8.1 Hz, 1H), 4.71-4.65 (m, 1H), 3.63-3.54 (m, 2H), 3.49-3.33 (m, 6H), 3.27-3.15 (m, 2H), 3.02-2.94 (m, 2H), 1.39-1.29 (m, 9H); ESI-MS (m/z, %): 463 (MH+, 100).
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:12])[N:4]([CH3:11])[C:5](S(C)=O)=[N:6][N:7]=1.[CH3:13][O-:14].[Na+]>CO>[NH2:1][C:2]1[C:3](=[O:12])[N:4]([CH3:11])[C:5]([O:14][CH3:13])=[N:6][N:7]=1
Reactant: Cn1c(S(C)=O)nnc(N)c1=O
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1nnc(N)c(=O)n1C
Temperature: 50 °C
Reaction time: 0.5 h

Procedure:
4.1 g of 6-amino-4-methyl-3-methylsulfinyl-1,2,4-triazin-5-one are suspended in 50 ml of absolute methanol, and 4.3 ml of 30% strength methanolic sodium methylate solution are added at room temperature. The reaction proceeds slightly exothermically and the temperature rises to 35° C. The solution is then stirred at 50° C. for 30 minutes, whereupon a colourless precipitate separates out of the clear yellow solution. The reaction mixture is evaporated and the residue is taken up in ethyl acetate and ice-water. The organic phase is separated off, dried with magnesium sulfate and evaporated. The residue is washed with a little methanol and dried. 1.6 g of 6-amino-4-methyl-3-methoxy-1,2,4-triazin-5-one with a melting point of 198°-199° C. are obtained in this manner.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[S:10])=[C:4]([CH3:11])[CH:3]=1.Cl.[CH3:13][NH:14][O:15][CH2:16][C:17]([OH:19])=[O:18].C(N(CC)CC)C>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([N:14]([CH3:13])[O:15][CH2:16][C:17]([OH:19])=[O:18])=[S:10])=[C:4]([CH3:11])[CH:3]=1
Reactant: CNOCC(=O)O
Reactant: Cc1cc(Cl)ccc1N=C=S
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: Cc1cc(Cl)ccc1NC(=S)N(C)OCC(=O)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 69.1 %

Procedure:
A mixture of 4-chloro-2-methylphenyl-isothiocyanate (12.8 g), N-methyl aminooxy acetic acid hydrochloride (10 g), triethylamine (7.5 g) and chloroform (100 mL) was heated at reflux for one hour, stirred at ambient temperature for one hour, then evaporated to dryness. The residue was dissolved in ethyl acetate (200 mL) and extracted with sodium bicarbonate saturated solution (2×200 mL). The aqueous extract was acidified with 6N HCl and extracted with ethyl acetate (2×300 mL). The organic phase was washed with water (200 mL), dried over anhydrous magnesium sulfate and evaporated to dryness to give 13.9 g of [[[[(4-Chloro-2-methylphenyl)amino]thioxomethyl]methylamino]oxy]acetic acid as a solid, m.p. 110-113° C. Mass spectrum (El, M.+) m/z 288/290. 1H-NMR (DMSO-d6; 400 MHz) δ□13.20 (br s, 1H), 10.12 (s, 1H), 7.34-7.19 (m, 3H),4.69 (q, 2H), 3.55 (s, 3H), and 2.17 ppm (s, 3H).
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[C:13]3[C:21](=[C:22]([C:24](=[O:26])[NH2:25])[CH:23]=2)[NH:20][C:19]2[CH:18]=[C:17]([N:27]4[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]4)[CH:16]=[CH:15][C:14]3=2)=[CH:7][C:6]=1[Cl:40].[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[C:24]([C:22]1[CH:23]=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([O:4][CH2:3][CH2:2][N:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)=[C:6]([Cl:40])[CH:7]=2)[CH:12]=[C:13]2[C:21]=1[NH:20][C:19]1[CH:18]=[C:17]([N:27]3[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]3)[CH:16]=[CH:15][C:14]2=1)(=[O:26])[NH2:25]
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc3c(c2)[nH]c2c(C(N)=O)cc(-c4ccc(OCCBr)c(Cl)c4)cc23)CC1
Reactant: C1COCCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCN(c2ccc3c(c2)[nH]c2c(C(N)=O)cc(-c4ccc(OCCN5CCOCC5)c(Cl)c4)cc23)CC1
Temperature: 75 °C
Yield: 89.4 %

Procedure:
tert-Butyl 4-(6-(4-(2-bromoethoxy)-3-chlorophenyl)-8-carbamoyl-9H-carbazol-2-yl)piperazine-1-carboxylate (342 mg, estimated purity 55%, ˜0.30 mmol, Example 409C) was dissolved in DMF (6 ml). Morpholine (0.5 ml, 5.7 mmol) and K2CO3 (160 mg, 1.16 mmol) were added and the mixture heated to 75° C. for 2 hour. The reaction mixture was poured into a separating funnel that was loaded with 100 ml water+25 ml saturated aq. NH4Cl solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, filtered and evaporated to dryness. Purification by prep HPLC gave 170 mg tert-butyl 4-(8-carbamoyl-6-(3-chloro-4-(2-morpholinoethoxy)phenyl)-9H-carbazol-2-yl)piperazine-1-carboxylate. MS (ESI) m/e+=634/636, m/e−=632/634 [1 Cl isotope pattern]. HPLC retention time 16.96 min. (Sunfire C18 3.5 μm, 3.0×150 mm column, 15 min gradient, 10-100% B, 0.5 mL/min. Solvent A: 5% CH3CN—95% H2O—0.1% TFA; Solvent B: 95% CH3CN—5% H2O—0.1% TFA), then isocratic at 100% B. 1H NMR (DMSO-d6) δ ppm 11.14 (s, 1H), 8.50 (d, 1H, J=1.3), 8.33 (b, 1H), 8.14 (d, 1H, J=1.5), 8.07 (d, 1H, J=8.8), 7.98 (d, 1H, J=2.3), 7.82 (dd, 1H, J=8.8, 2.3), 7.51 (b, 1H), 7.31 (d, 1H, J=8.8), 7.25 (d, 1H, J=2.0), 6.95 (dd, 1H, J=8.8, 2.0), 4.26 (t, 2H, J=5.8), 3.63-3.59 (m, 4H), 3.53 (b, 4H), 3.21-3.17 (m, 4H), 2.79 (t, 2H, J=5.8), 2.58-2.54 (m, 4H), 1.46 (s, 9H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][F:17])[C:11](=[O:18])[CH2:10]2)=[C:6]([F:8])[CH:7]=1.N1C=CC=CC=1.Cl[C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27]>ClCCl>[CH2:29]([O:28][C:26]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][F:17])[C:11](=[O:18])[CH2:10]2)=[C:6]([F:8])[CH:7]=1)=[O:27])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: Nc1ccc(N2CCN(CCF)C(=O)C2)c(F)c1
Reactant: O=C(Cl)OCc1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(Nc1ccc(N2CCN(CCF)C(=O)C2)c(F)c1)OCc1ccccc1
Reaction time: 0.17 h

Procedure:
5-Amino-2-(4-[2-fluoroethyl]-3-oxopiperazin-1-yl)fluorobenzene (2.6 g) is dissolved in dry dichloromethane (50 ml) under argon. Pyridine (1.03 ml) is added, and the mixture cooled to −20°. Benzyl chloroformate (1.6 ml) is added and the mixture stirred for 10 minutes at −20°, before allowing the temperature to rise to 20-25° over 1.5 hours. The solvents are removed and the residue is dissolved in dichloromethane and washed with sodium bicarbonate solution. After drying over magnesium sulfate and removal of the solvent, the residue is chromatographed (silica, eluting with a gradient increasing in polarity from 0 to 5% methanol in dichloromethane) to give 5-benzyloxycarbonylamino-2-(4-[2 fluoroethyl]-3-oxopiperazin-1-yl)fluorobenzene.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:16]([NH:18][CH2:19][CH3:20])=[O:17])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14]Br)[CH:9]=2)=[CH:6][N:7]=1.[C@@H:21]1([NH2:30])[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22]1.C(N(C(C)C)CC)(C)C>C(#N)C>[NH2:1][C:2]1[C:3]([C:16]([NH:18][CH2:19][CH3:20])=[O:17])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][NH:30][C@@H:21]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH2:23][CH2:22]3)[CH:9]=2)=[CH:6][N:7]=1
Reactant: N[C@H]1CCc2ccccc21
Reactant: CCNC(=O)c1nc(-c2cccc(CBr)c2)cnc1N
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CCNC(=O)c1nc(-c2cccc(CN[C@H]3CCc4ccccc43)c2)cnc1N
Reaction time: 7 h
Yield: 38.8 %

Procedure:
The 3-amino-6-[3-(bromomethyl)phenyl]-N-ethylpyrazine-2-carboxamide (112 mg, 1.0 eq) was dissolved in acetonitrile (5 mL) and treated with (1S)-2,3-dihydro-1H-inden-1-amine (133.8 mg, 3.0 eq), diisopropylethylamine (69.3 mg, 1.6 eq) at ambient temperature. After being stirred for 7 h, the white suspension was filtered on Celite and concentrated in vacuo. The resulting residue was purified by flash column chromatography to give the 3-amino-6-(3-{[(1S)-2,3-dihydro-1H-inden-1-ylamino]methyl}phenyl)-N-ethylpyrazine-2-carboxamide (50.2 mg, 39% yield): 1H NMR (400 MHz, CD3OD): δ 8.72 (s, 1H), 8.21 (s, 1H), 8.11 (d, 1H), 7.61 (d, 1H), 7.58 (t, 1H), 7.49 (d, 1H), 7.39 (d, 2H), 7.39 (d, 2H), 7.37 (m, 1H), 4.38 (s, 2H), 3.47 (m 1H), 3.23 (m, 1H), 3.01 (m, 1H), 2.64 (m, 1H), 2.39 (m, 1H); MS (EI) for C23H25N5O: 388.22 (MH+).
Reaction SMILES: [C:1]([O:5][C:6](=[O:35])[N:7]([CH2:24][CH2:25][CH2:26][NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:8][C:9]1[CH:14]=[CH:13][C:12](B2OC(C)(C)C(C)(C)O2)=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:36][O:37][C:38](=[O:44])[C:39](I)=[CH:40][O:41][CH3:42].[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:36][O:37][C:38](=[O:44])[C:39]([C:12]1[CH:13]=[CH:14][C:9]([CH2:8][N:7]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:35])[CH2:24][CH2:25][CH2:26][NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[CH:10][CH:11]=1)=[CH:40][O:41][CH3:42]
Reactant: COC=C(I)C(=O)OC
Reactant: CC(C)(C)OC(=O)NCCCN(Cc1ccc(B2OC(C)(C)C(C)(C)O2)cc1)C(=O)OC(C)(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: COC=C(C(=O)OC)c1ccc(CN(CCCNC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)cc1
Temperature: 80 °C
Yield: 91.3 %

Procedure:
A mixture of (3-tert-butoxycarbonylamino-propyl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-carbamic acid tert-butyl ester (6.00 g, 12.25 mmol), 2-iodo-3-methoxy-acrylic acid methyl ester (4.45 g, 18.38 mmol), K3PO4 (7.79 g, 36.75 mmol), Pd(PPh3)4 (0) (0.68 g, 0.61 mmol), dioxane (60 mL) and water (12 mL) was degassed and heated at 80° C. for 20 h under argon atmosphere. The reaction mixture was diluted with EtOAc (500 mL), washed with water (300 mL) and brine (300 mL). The organic solution was concentrated and purified by flash chromatography (0%-30% EtOAc in heptane) to give desired product (5.35 g, 91%) as brown oil. 1NMR (300 MHz, CDCl3): δ 7.56 (s, 1H), 7.30 (d, J=8.1 Hz, 2H), 7.20 (br.d, 2H), 5.20 (br.s, 0.5H), 4.62 (br.s, 0.5H), 4.39 (br, 2H), 3.86 (s, 3H), 3.74 (s, 3H), 3.27 (m, 2H), 3.08 (m, 2H), 1.62 (m, 2H), 1.50 (br.d, 9H), 1.43 (s, 9H). LCMS (EI) m/z: 501 (M+Na+).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12](=[O:17])[CH2:11][CH2:10]2.[SH:18][C:19]1[S:20][C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[N:23]=1>>[S:20]1[C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[N:23]=[C:19]1[S:18][CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12](=[O:17])[CH2:11][CH2:10]2
Reactant: Sc1nc2ccccc2s1
Reactant: O=C1CCc2cc(OCCCCCl)ccc2N1
Product: O=C1CCc2cc(OCCCCSc3nc4ccccc4s3)ccc2N1

Procedure:
Prepared analogous to Example 1 from 6-(4-chlorobutoxy)-3,4-dihydro-carbostyril (m.p.: 147°-148° C.) and 2-mercapto-benzthiazole.
Reaction SMILES: [O:1]=[C:2]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:6]2[S:14][C:15]([C:23](O)=[O:24])=[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:5]=2[CH:4]=[CH:3]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:40][N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1>C(Cl)Cl>[CH3:40][N:41]1[CH2:46][CH2:45][N:44]([C:23]([C:15]2[S:14][C:6]3[N:7]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[C:2](=[O:1])[CH:3]=[CH:4][C:5]=3[C:16]=2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:24])[CH2:43][CH2:42]1
Reactant: CN1CCNCC1
Reactant: O=C(O)c1sc2c(ccc(=O)n2-c2ccccc2)c1-c1ccccc1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: ClCCl
Product: CN1CCN(C(=O)c2sc3c(ccc(=O)n3-c3ccccc3)c2-c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 65.8 %

Procedure:
To a suspension of the compound of Example 59 (100 mg, 0.29 mmol) in DCM (2 mL) was added EDC (67 mg, 0.348 mmol) and HOBT (43 mg, 0.32 mmol) and the mixture stirred at r.t. for 15 minutes. A solution N-methyl piperazine (28 mg, 0.32 mmol) in DCM (0.5 mL) was added and the reaction stirred at r.t. for 18 h. The reaction mixture was diluted with DCM (10 mL), washed with water (2×5 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by chromatography on silica (0–20% THF in DCM) to give the title compound as an off-white solid (82 mg). δH (DMSO-d6) 7.67 (1H, dd, J 10, 1 Hz), 7.62–7.52 (3H, m), 7.51–7.40 (5H, m), 7.35–7.31 (2H, m), 6.51 (1H, dd, J 10, 1 Hz), 2.44 (8H, m), 1.88 (3H, s). LCMS (ES+) RT 2.18 minutes, 430 (M+H)+.
Reaction SMILES: [OH:1][N:2]=[C:3]([C:9]#[N:10])[C:4]([O:6][CH2:7][CH3:8])=[O:5].C(N(CC)CC)C.[C:18]1([CH3:28])[CH:23]=[CH:22][C:21]([S:24](Cl)(=[O:26])=[O:25])=[CH:20][CH:19]=1>C(OCC)(=O)C>[C:18]1([CH3:28])[CH:23]=[CH:22][C:21]([S:24]([O:1][N:2]=[C:3]([C:9]#[N:10])[C:4]([O:6][CH2:7][CH3:8])=[O:5])(=[O:26])=[O:25])=[CH:20][CH:19]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CCOC(=O)C(C#N)=NO
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CCOC(=O)C(C#N)=NOS(=O)(=O)c1ccc(C)cc1
Reaction time: 8 h
Yield: 94.1 %

Procedure:
In ethyl acetate (50 ml) are dissolved ethyl 2-hydroxyimino-2-cyanoacetate (7.1 g) and triethylamine (7.0 ml). To the solution is added p-toluenesulfonyl chloride (9.5 g) with stirring under ice-cooling, and the mixture is stirred for 2 hours and allowed to stand overnight. The reaction mixture is filtered and the filtrate is concentrated. To the residue is added cyclohexane and the resulting crystals are separated by filtration and dried to give ethyl 2-(p-toluenesulfonyloxyimino)-2-cyanoacetate (13.9 g), melting point: 84°-87° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][CH2:9][CH2:8][CH2:7]2.[C:12]1([CH2:18][CH2:19][CH:20]=O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl>CO>[C:12]1([CH2:18][CH2:19][C:20]2[N:10]3[C:11]4[C:6]([CH2:7][CH2:8][CH2:9]3)=[CH:5][CH:4]=[CH:3][C:2]=4[N:1]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: Nc1cccc2c1NCCC2
Reactant: O=CCCc1ccccc1
Agent: Cl
Solvent: CO
Product: c1ccc(CCc2nc3cccc4c3n2CCC4)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Thirty-five grams of 8-amino-1,2,3,4-tetrahydroquinoline was dissolved in methanol (700 mL) and, following the addition of 3-phenylpropionaldehyde (37.4 mL) and 1N HCl (7 mL) and subsequent stirring at room temperature for 1 hr, silica gel (75 g) was added to the reaction solution and the solvent was removed under reduced pressure. The residue was heated at 100° C. for 1 hr, purified by silica gel column chromatography (eluent: dichloromethane/ethyl acetate) and recrystallized with ethyl acetate to yield the titled compound as pale yellow crystals (19.3 g).
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=2)[O:3]1.Cl[C:18]([O:20][CH2:21][CH2:22][O:23][CH3:24])=[O:19].CN1CCOCC1>O1CCCC1>[CH3:24][O:23][CH2:22][CH2:21][O:20][C:18](=[O:19])[NH:15][C:12]1[CH:13]=[CH:14][C:9]([B:4]2[O:3][C:2]([CH3:16])([CH3:1])[C:6]([CH3:7])([CH3:8])[O:5]2)=[CH:10][CH:11]=1
Reactant: CC1(C)OB(c2ccc(N)cc2)OC1(C)C
Reactant: COCCOC(=O)Cl
Solvent: C1CCOC1
Solvent: CN1CCOCC1
Product: COCCOC(=O)Nc1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
107 mg of 4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenylamine (0.48 mmol) were dissolved in tetrahydrofuran. 96 mg of 2-methoxyethyl chloroformate (0.68 mmol) and 79 mg of N-methylmorpholine (0.78 mmol) were added at room temperature. The mixture was left to stir at room temperature for 1 day, precipitated solid was filtered off and the solvent was removed under reduced pressure. This gave a yellowish oil which was used without further purification in the next reaction.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.Br[C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([S:20]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)(=[O:22])=[O:21])[CH:15]=[C:14]2[C:29]1[CH2:30][CH2:31][N:32]([CH3:35])[CH2:33][CH:34]=1.C(O)CC.C([O-])([O-])=O.[Na+].[Na+]>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:35][N:32]1[CH2:33][CH:34]=[C:29]([C:14]2[C:13]3[C:17](=[CH:18][CH:19]=[C:11]([C:4]4[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=4)[CH:12]=3)[N:16]([S:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)(=[O:22])=[O:21])[CH:15]=2)[CH2:30][CH2:31]1
Reactant: CN1CC=C(c2cn(S(=O)(=O)c3ccccc3)c3ccc(Br)cc23)CC1
Reactant: OB(O)c1cccnc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCCO
Solvent: O
Product: CN1CC=C(c2cn(S(=O)(=O)c3ccccc3)c3ccc(-c4ccncc4)cc23)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 43.1 %

Procedure:
Into a 100 mL 3-necked round bottom flask was placed pyridin-3-ylboronic acid (200 mg, 1.63 mmol), 5-bromo-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1-(phenylsulfonyl)-1H-indole (470 mg, 1.08 mmol), and n-propanol (140 mL). The mixture was stirred at room temperature for 30 min during which time the solids dissolved. A solution of Na2CO3 (430 mg, 4.06 mmol) in water (5 mL) was then added, followed by the addition of Pd(PPh3)4 (130 mg, 0.108 mmol). The resulting solution was stirred at reflux temperature overnight, and then concentrated. The residue was dissolved in water (10 mL), and the resulting solution was extracted diethylether (2×50 mL). The organic layers were combined and the residue was purified by column chromatography using a 1:5 dichloromethane/methanol solvent system to afford 200 mg (42.5%) of 3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1-(phenylsulfonyl)-5-(pyridin-4-yl)-1H-indole as a deep yellow solid. 1H NMR (CDCl3) δ 8.69 (d, 2H), 8.12 (d, 1H), 7.93 (t, 3H), 7.60 (d, 3H), 7.48 (d×d, 4H), 6.18 (s, 1H), 2.85 (2H), 1.52 (2H), 1.25 (3H), 0.87 (2H). LC/MS (EI) tR 2.18, m/z 430.0 (M++1)