Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[N:10]1[C:22]2[C:21]3[CH:20]=[CH:19][CH:18]=[C:17]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])[C:16]=3[N:15]=[C:14](Cl)[C:13]=2[CH2:12][CH2:11]1.[NH2:30][CH2:31][CH2:32][CH2:33][OH:34]>>[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[N:10]1[C:22]2[C:21]3[CH:20]=[CH:19][CH:18]=[C:17]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])[C:16]=3[N:15]=[C:14]([NH:30][CH2:31][CH2:32][CH2:33][OH:34])[C:13]=2[CH2:12][CH2:11]1
Reactant: COc1ccc(N2CCc3c(Cl)nc4c(OCC(F)(F)F)cccc4c32)c(C)c1
Reactant: NCCCO
Product: COc1ccc(N2CCc3c(NCCCO)nc4c(OCC(F)(F)F)cccc4c32)c(C)c1

Procedure:
1-(2-Methyl-4-methoxyphenyl)-4-chloro-6-β,β,β-trifluoroethoxy-2,3-dihydropyrrolo[3,2-c]quinoline(700 mg, 1.7 mmol) was dissolved in 3-amino-1-propanol(5.0 ml), and reacted at the same condition of Step 3 in the Example 49 to obtain 470 mg of desired compound as solid in 60% of yield.
Reaction SMILES: Cl[C:2]1[N:23]=[C:5]2[C:6]([NH:10][C:11]3[C:12]([N:17]([CH3:22])[S:18]([CH3:21])(=[O:20])=[O:19])=[N:13][CH:14]=[CH:15][CH:16]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[N:24]1([CH2:29][CH2:30][O:31][C:32]2[CH:37]=[CH:36][C:35]([NH2:38])=[CH:34][CH:33]=2)[CH2:28][CH2:27][CH2:26][CH2:25]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:22][N:17]([C:12]1[C:11]([NH:10][C:6]2[C:5]3[N:4]([N:3]=[C:2]([NH:38][C:35]4[CH:36]=[CH:37][C:32]([O:31][CH2:30][CH2:29][N:24]5[CH2:28][CH2:27][CH2:26][CH2:25]5)=[CH:33][CH:34]=4)[N:23]=3)[CH:9]=[CH:8][CH:7]=2)=[CH:16][CH:15]=[CH:14][N:13]=1)[S:18]([CH3:21])(=[O:20])=[O:19]
Reactant: Nc1ccc(OCCN2CCCC2)cc1
Reactant: CN(c1ncccc1Nc1cccn2nc(Cl)nc12)S(C)(=O)=O
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: CN(c1ncccc1Nc1cccn2nc(Nc3ccc(OCCN4CCCC4)cc3)nc12)S(C)(=O)=O

Procedure:
N-Methyl-N-(3-{2-[4-(2-pyrrolidin-1-yl-ethoxy)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino}-pyridin-2-yl)-methanesulfonamide was prepared from N-[3-(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-pyridin-2-yl]-N-methyl-methanesulfonamide (75.0 mg, 0.212 mmol) and 4-(2-pyrrolidin-1-yl-ethoxy)-phenylamine (53.0 mg, 0.257 mmol) (prepared as described in J. Med. Chem., 2006, 49, 4451-4454) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (25.0 mg, 0.0457 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a brown foam (0.023 g, 21%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.09 (dd, J=4.6, 1.5 Hz, 1H), 8.05 (d, J=6.5 Hz, 1H), 7.78 (dd, J=8.1, 1.4 Hz, 1H), 7.55 (s, 1H), 7.50 (d, J=9.0 Hz, 2H), 7.28-7.23 (m, 1H), 7.13 (d, J=7.7 Hz, 1H), 6.93 (d, J=9.0 Hz, 2H), 6.74 (t, J=7.2 Hz, 1H), 6.69 (s, 1H), 4.11 (t, J=6.1 Hz, 2H), 3.33 (s, 3H), 3.10 (s, 3H), 2.09 (t, J=6.0 Hz, 2H), 2.67-2.57 (m, 4H), 1.87-1.77 (m, 4H). MS=523 (MH)+.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:14]([NH2:16])=[O:15])=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=2)[N:6]=1.F[C:18]1[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][C:19]=1[N+:26]([O-:28])=[O:27].CN(C)C=O.C(=O)([O-])[O-].[Cs+].[Cs+]>O>[Cl:13][C:10]1[CH:9]=[CH:8][C:7]([C:5]2[N:6]=[C:2]([NH:1][C:18]3[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][C:19]=3[N+:26]([O-:28])=[O:27])[S:3][C:4]=2[C:14]([NH2:16])=[O:15])=[CH:12][CH:11]=1
Reactant: O=Cc1ccc(F)c([N+](=O)[O-])c1
Reactant: NC(=O)c1sc(N)nc1-c1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: NC(=O)c1sc(Nc2ccc(C=O)cc2[N+](=O)[O-])nc1-c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 101.8 %

Procedure:
To a mixture of 0.10 g (0.39 mmole) of 2-amino-4-(4-chloro-phenyl)-thiazole-5-carboxylic acid amide (V.18), 0.07 g (0.39 mmole) of 4-fluoro-3-nitrobenzaldehyde and 2 mL of dimethylformamide was added 0.19 g (0.59 mmole) of cesium carbonate. The mixture was heated at 120 degrees for 6 hours and then cooled. Water was then added and the suspension stirred at room temperature for one hour. The precipitate was collected by filtration, washed with water and dried under vacuum to give 0.16 g of 4-(4-chloro-phenyl)-2-(4-formyl-2-nitro-phenylamino)-thiazole-5-carboxylic acid amide (VI.18a).
Reaction SMILES: CN(C)[CH:3]=[O:4].P(Cl)(Cl)(Cl)=O.[CH3:11][O:12][CH2:13][C:14]([N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[C:18]1[CH3:26])([CH3:16])[CH3:15]>ClCCl>[CH3:11][O:12][CH2:13][C:14]([N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]([CH:3]=[O:4])=[C:18]1[CH3:26])([CH3:16])[CH3:15]
Reactant: CN(C)C=O
Reactant: COCC(C)(C)n1c(C)cc2ccccc21
Solvent: ClCCl
Solvent: O=P(Cl)(Cl)Cl
Product: COCC(C)(C)n1c(C)c(C=O)c2ccccc21
Temperature: 0 °C
Reaction time: 3 h
Yield: 57 %

Procedure:
To a solution of 2 ml anhydrous N,N-dimethylformamide dissolved in 80 ml anhydrous dichloromethane was added phosphoryl trichloride (5 g, 32.6 mmol) at 0° C. The resultant reaction mixture was allowed to stirred at 0° C. for 3 hours. 1-(1-methoxy-2-methylpropan-2-yl)-2-methyl-1H-indole (800 mg, 3.7 mmol) was added dropwise at 0° C. Then the resulting reaction mixture was allowed to stir for 1 hour at 0° C., and then warmed to the ambient temperature. The reaction mixture was allowed to stir for 24 hours at room temperature. The reaction mixture was quenched with saturated sodium acetate. The pH was adjusted to around 8 by progressively adding 2N sodium hydroxide below 0° C., extracted with dichloromethane (100 mL×3). The combined organic phase was dried by anhydrous sodium sulphate, and then filtered. The filtrate was concentrated and purified by column chromatograph on silica gel eluted with (petrol ether/acetic ester 10:1→5:1→2:1) to give 1-(1-methoxy-2-methylpropan-2-yl)-2-methyl-1H-indole-3-carbaldehyde (510 mg, 57%) as a light yellow oil. LCMS (M+H) m/z: calcd. 245.14. found 245.9.
Reaction SMILES: [C:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13](Cl)=[O:14])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:16]([O:18][CH:19]([O:24][CH2:25][CH3:26])[CH2:20][CH2:21][CH2:22][NH2:23])[CH3:17].C(N(CC)CC)C.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[CH2:25]([O:24][CH:19]([O:18][CH2:16][CH3:17])[CH2:20][CH2:21][CH2:22][NH:23][C:13]([N:10]1[CH2:11][CH2:12][CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:8][CH2:9]1)=[O:14])[CH3:26]
Reactant: CCOC(CCCN)OCC
Reactant: O=C(Cl)N1CCC(c2ccccc2)CC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(CCCNC(=O)N1CCC(c2ccccc2)CC1)OCC
Reaction time: 8 h

Procedure:
A solution of 895 mg (4 mmol) of 4-phenylpiperidine-1-carbonylchloride in 4 mL dichloromethane is added to 0.69 mL (4 mmol) 4,4-diethoxybutylamine and 1.68 mL (12 mmol) of triethylamine dissolved in 20 mL of dichloromethane. The mixture is stirred overnight. 20 mL of saturated sodium carbonate solution is added. The organic phase is separated, dried with sodium sulfate and the solvent evaporated.
Reaction SMILES: [Li]CCCC.Br[C:7]1[CH:18]=[CH:17][C:10]([CH2:11][N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[C:9]([Cl:19])[CH:8]=1.[O:20]=[C:21]1[CH2:24][CH:23]([C:25]([OH:27])=[O:26])[CH2:22]1>C1COCC1>[Cl:19][C:9]1[CH:8]=[C:7]([C:21]2([OH:20])[CH2:24][CH:23]([C:25]([OH:27])=[O:26])[CH2:22]2)[CH:18]=[CH:17][C:10]=1[CH2:11][N:12]1[CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: O=C1CC(C(=O)O)C1
Reactant: Clc1cc(Br)ccc1CN1CCCC1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: O=C(O)C1CC(O)(c2ccc(CN3CCCC3)c(Cl)c2)C1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
A 2.5 M solution of n-BuLi in hexanes (101 mL, 254 mmol) was added over 15 min to a solution of 1-(4-bromo-2-chlorobenzyl)pyrrolidine (69.6 g, 254 mmol) in absolute THF (450 ml) under a flow of nitrogen at −78° C. The reaction mixture was stirred at −78° C. for 30 min. Then a −78° C. chilled solution of 3-oxocyclobutanecarboxylic acid (14.4 g, 126.7 mmol) in absolute THF (150 ml) was added drop wise for 10 min at −78° C. The mixture was warmed to RT slowly and left stirring for 18 hrs and the resulting solution was used. LRMS m/z Calcd for C18H20NClO3, 309.8, found, 308.1 (M−H) APCI.
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@:15]2([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([CH2:24][C:25]4[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH3:33])=[CH:27][CH:26]=4)[CH:18]=3)[O:16][C@@:12]3([CH2:34][O:35]C(C4C=CC=CC=4)[O:37][C@H:11]3[C@@H:10]1[O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[CH2:13][O:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[Na]>C(#N)C>[CH2:45]([O:44][C@@H:10]1[C@@H:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C@:15]2([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([CH2:24][C:25]4[CH:26]=[CH:27][C:28]([O:31][CH2:32][CH3:33])=[CH:29][CH:30]=4)[CH:18]=3)[O:16][C@@:12]([CH2:34][OH:35])([CH2:13][O:14]2)[C@H:11]1[OH:37])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1
Reactant: CCOc1ccc(Cc2cc([C@@]34OC[C@]5(COC(c6ccccc6)O[C@H]5[C@H](OCc5ccccc5)[C@H]3OCc3ccccc3)O4)ccc2Cl)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na]
Solvent: CC#N
Solvent: O
Product: CCOc1ccc(Cc2cc([C@]34OC[C@](CO)(O3)[C@@H](O)[C@H](OCc3ccccc3)[C@H]4OCc3ccccc3)ccc2Cl)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 69.3 %

Procedure:
To a solution of (4aS,7S,8R,9S,9aS)-8,9-bis(benzyloxy)-7-(4-chloro-3-(4-ethoxybenzyephenye-2-phenylhexahydro-4a,7-epoxy[1,3]dioxino[5,4-c]oxepine 28c (17.56 g, 27.3 mmol) in acetonitrile (40 mL) was added p-toluenesulfonic acid monohydrate (9.4 g, 54.6 mmol) at room temperature. The mixture was stirred at room temperature for 12 hours and adjusted with saturated aqueous sodium bicarnonate till pH becomes 7. The resulting mixture was extracted with ethyl actate (100 mL×3). The combined organic phases were washed with saturated aqueous sodium chloride (30 mL×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=3/1 to give the title compound 28d as a yellow solid (11.68 g, 76.0%). The compound was characterized by the following spectroscopic data: 1H NMR (600 MHz, CDCl3) δ (ppm): 7.35 (d, 1H), 7.29-7.26 (m, 4H), 7.24 (d, 3H), 7.11 (m, 3H), 6.99 (d, 2H), 6.82 (d, 2H), 6.67 (d, 2H), 4.79 (d, 1H), 4.62 (d, 1H), 4.15 (m, 2H), 3.99 (d, 1H), 3.90 (m, 4H), 3.76 (m, 4H), 3.57 (d, 2H), 1.31 (t, 3H).
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12]([CH2:14][NH:15][CH2:16][CH2:17][O:18][CH3:19])[CH:13]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:19][O:18][CH2:17][CH2:16][NH:15][CH2:14][C:12]1[CH:13]=[C:8]([NH2:7])[CH:9]=[N:10][CH:11]=1
Reactant: COCCNCc1cncc(NC(=O)OC(C)(C)C)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COCCNCc1cncc(N)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 35 %

Procedure:
To a stirred solution of 56 (0.4 g, 1.42 mmol) in DCM (3 mL) was added TFA (3 mL) at 0° C. and stirred at rt for 3 h. The reaction mixture was concentrated, the residue was dissolved in MeOH, basified with Ambersep 900-OH resin, filtered to separate the resin and the filtrate concentrated to obtain the desired amine (90 mg, 88%) as a brown color viscous liquid. Rf: 0.1 (10% MeOH/CHCl3); (m/z):182 [M+1]+; 1H NMR (400 MHz, DMSO-d6) δ 7.77 (1H, d, J=2.4 Hz), 7.66 (1H, d, J=1.6 Hz), 6.86 (1H, d, J=2 Hz), 5.19 (2H, m), 3.66 (2H, s), 3.39-3.36 (3H, m), 3.22 (3H, s), 2.62-2.59 (2H, m), 1.93-1.92 (1H, br s).
Reaction SMILES: CC1C=CC(S(O[CH2:12][C@@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2[S:18]([C:21]2[CH:29]=[CH:28][C:27]3[N:26]4[CH2:30][C:31]([CH3:35])([CH3:34])[CH2:32][N:33]=[C:25]4[C:24]4([O:40]CCCO4)[C:23]=3[CH:22]=2)(=[O:20])=[O:19])(=O)=O)=CC=1.[CH:41]1([NH2:47])[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1>C1COCC1>[CH:41]1([NH:47][CH2:12][C@@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2[S:18]([C:21]2[CH:29]=[CH:28][C:27]3[N:26]4[CH2:30][C:31]([CH3:34])([CH3:35])[CH2:32][N:33]=[C:25]4[C:24](=[O:40])[C:23]=3[CH:22]=2)(=[O:19])=[O:20])[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1
Reactant: Cc1ccc(S(=O)(=O)OC[C@@H]2CCCN2S(=O)(=O)c2ccc3c(c2)C2(OCCCO2)C2=NCC(C)(C)CN23)cc1
Reactant: NC1CCCCC1
Solvent: C1CCOC1
Product: CC1(C)CN=C2C(=O)c3cc(S(=O)(=O)N4CCC[C@H]4CNC4CCCCC4)ccc3N2C1
Temperature: 70 °C
Reaction time: 8 h
Yield: 46.2 %

Procedure:
To a solution of {(2S)-1-[(3′,3′-dimethyl-3′,4′-dihydro-2′H-spiro[1,3-dioxane-2,10′-pyrimido[1,2-a]indol]-8′-yl)sulfonyl]pyrrolidin-2-yl}methyl 4-methylbenzenesulfonate (0.100 g, 0.170 mmol) in THF (2 mL) was added cyclohexylamine (0.034 g, 0.340 mmol) and the reaction was stirred at 70° C. overnight. Additional cyclohexylamine (0.088 g, 0.850 mmol) was added to the reaction and stirred at 100° C. for 2 days. The reaction was quenched with water and extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered, concentrated and purified on Biotage Si 12+M cartridge silica gel eluting with acetone/hexane (35/65). The resulting product was dissolved in CH2Cl2 (2 mL) and methanesulfonic acid (2 mL) was added and the solution was stirred at rt overnight. The reaction mixture was poured onto ice, basified to pH 11 with ammonium hydroxide and extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered, concentrated and purified on Biotage Si 12+M cartridge silica gel eluting with acetone/hexane (35/65) to give the title compound as a yellow foam (0.036 g, 46%). NMR (400 Mz, DMSO-d6): consistent. MS: (ESI+) m/z 459.3 [M+H].
Reaction SMILES: [N+:1]([C:4]1[CH:19]=[CH:18][C:7]2[N:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=3)[O:10][C:6]=2[CH:5]=1)([O-])=O.[Cl-].[NH4+]>C(O)C.O.[Fe]>[C:14]1([CH3:17])[CH:13]=[CH:12][C:11]([C:9]2[O:10][C:6]3[CH:5]=[C:4]([NH2:1])[CH:19]=[CH:18][C:7]=3[N:8]=2)=[CH:16][CH:15]=1
Reactant: Cc1ccc(-c2nc3ccc([N+](=O)[O-])cc3o2)cc1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: Cc1ccc(-c2nc3ccc(N)cc3o2)cc1
Yield: 3.8 %

Procedure:
To 6-nitro-2-p-tolylbenzo[d]oxazole (2.1 g, 8.27 mmol) in ethanol:water 2:1 v/v (60 mL) at 70° C. was added iron powder (2.14 g, 38.3 mmol) and ammonium chloride (819 mg, 15.3 mmol). The suspension was stirred at reflux for 16 h. After cooling, the solution was filtered through a pad of Celite® and washed with ethanol. After evaporation of the solvent, the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried over anhydrous MgSO4 and evaporated. The resulting solid was purified by column chromatography eluting with ethyl acetate:hexanes 1:3 v/v to afford 70 mg (4%) of the title compound (LCMS RT=6.12 min, MH+ 223.1)
Reaction SMILES: ClS([N:5]=[C:6]=[O:7])(=O)=O.[N-]=C=O.[NH2:11][C:12]1[N:17]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([NH2:24])[CH:19]=2)[CH2:16][N:15]=[C:14]2[O:25][CH:26]=[CH:27][C:13]=12>>[NH2:11][C:12]1[N:17]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([NH:24][C:6]([NH2:5])=[O:7])[CH:19]=2)[CH2:16][N:15]=[C:14]2[O:25][CH:26]=[CH:27][C:13]=12
Reactant: NC1=c2ccoc2=NCN1c1cccc(N)c1
Reactant: O=C=NS(=O)(=O)Cl
Agent: [N-]=C=O
Product: NC(=O)Nc1cccc(N2CN=c3occc3=C2N)c1

Procedure:
The compound was prepared following the procedure described in Example 232(b), using chlorosulfonyl isocyanate as the isocyanate of choice, and 4-Amino-3-(3-aminophenyl)furo[2,3-d]pyrimidine (10) as the diamine of choice. MS(ES) m/e 270 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:27])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)=[CH:17][CH:16]=2)[CH:7]=1.[C:28]1([S:34](Cl)(=[O:36])=[O:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C(N(CC)CC)C>[CH3:1][O:2][C:3](=[O:27])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][N:13]([S:34]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)(=[O:36])=[O:35])[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)=[CH:17][CH:16]=2)[CH:7]=1
Reactant: COC(=O)CCc1cccc(CNCc2ccc(-c3cccnc3)cc2)c1
Reactant: O=S(=O)(Cl)c1ccccc1
Solvent: CCN(CC)CC
Product: COC(=O)CCc1cccc(CN(Cc2ccc(-c3cccnc3)cc2)S(=O)(=O)c2ccccc2)c1

Procedure:
The title compound of Step B was prepared from 3-{3-[(4-pyridin-3-yl-benzylamino)-methyl]-phenyl}-propionic acid methyl ester, of Step A, and benzenesulfonyl chloride following the method described in Example 1, Step B using triethylamine in place of N,N-diisopropylethylamine. 1H NMR (400 MHz, CDCl3) δ8.79 (s, 1H), 8.58 (d, 1H), 7.87 (m, 3H), 7.61 (m, 1H), 7.54 (m, 2H), 7.40 (m, 3H), 7.18 (m, 3H), 7.03 (d, 1H), 6.88 (d, 1H), 6.79 (s, 1H), 4.36 (s, 2H), 4.33 (s, 2H), 3.65 (s, 3H), 2.79 (t, 2H), 2.48 (t, 2H); MS 501 (M+1).
Reaction SMILES: [CH2:1]([O:15][C:16]1[O:20][C:19]([C:21]([OH:23])=[O:22])=[CH:18][CH:17]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[Cl:24][C:25]([Cl:29])([Cl:28])[CH2:26]O>>[CH2:1]([O:15][C:16]1[O:20][C:19]([C:21]([O:23][CH2:26][C:25]([Cl:29])([Cl:28])[Cl:24])=[O:22])=[CH:18][CH:17]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCCCCCCCOc1ccc(C(=O)O)o1
Reactant: OCC(Cl)(Cl)Cl
Product: CCCCCCCCCCCCCCOc1ccc(C(=O)OCC(Cl)(Cl)Cl)o1

Procedure:
The title compound was prepared as described in Example 1 starting from 0.228 g (0.7 mmol) of 5-(tetradecyloxy)furan-2-carboxylic acid and 0.196 mL (2.04 mmol) of 2,2,2-trichloroethanol. 1H NMR (400 MHz, DMSO-d6) δ: 7.4 (d, 1H), 5.74 (d, 1H), 5.03 (s, 2H), 4.19 (t, 2H), 1.7 (p, 2H), 1.2-1.5 (m, 22H), 0.85 (t, 3H).
Reaction SMILES: C([O:8][C:9]1[CH:18]=[CH:17][C:12]2[CH2:13][O:14][B:15]([OH:16])[C:11]=2[CH:10]=1)C1C=CC=CC=1.[H][H]>CO.[Pd]>[OH:8][C:9]1[CH:18]=[CH:17][C:12]2[CH2:13][O:14][B:15]([OH:16])[C:11]=2[CH:10]=1
Reactant: [H][H]
Reactant: OB1OCc2ccc(OCc3ccccc3)cc21
Agent: [Pd]
Solvent: CO
Product: OB1OCc2ccc(O)cc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 98 %

Procedure:
H178 (13 mmol) was dissolved in MeOH (300 mL). To this solution under nitrogen was added 10% Pd/C (200 mg). The reaction mixture was vacuumed and backfilled hydrogen for 3 times, then stirred overnight at room temperature. After filtration and rotary evaporation, the residue was purified by recrystallization to give H181 (1.98 mg, 98% yield). 1H NMR (300 MHz, DMSO-d6): δ 9.29 (s, 1H), 9.04 (s, 1H), 7.18 (d, J=8.4 Hz, 2H), 6.87 (dd, J=8.1 & 2.4 Hz, 1H) and 4.86 (s, 2H) ppm. Mp 133-135° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]([CH3:14])[CH:7]=[C:6]2[C:15]1[N:29](S(C2C=CC(C)=CC=2)(=O)=O)[C:18]2=[N:19][CH:20]=[CH:21][C:22]([CH2:23][NH:24][CH2:25][CH2:26][O:27][CH3:28])=[C:17]2[CH:16]=1.[OH-].[K+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]([CH3:14])[CH:7]=[C:6]2[C:15]1[NH:29][C:18]2=[N:19][CH:20]=[CH:21][C:22]([CH2:23][NH:24][CH2:25][CH2:26][O:27][CH3:28])=[C:17]2[CH:16]=1
Reactant: COCCNCc1ccnc2c1cc(-c1cn(C)c3cc(OC)c(OC)cc13)n2S(=O)(=O)c1ccc(C)cc1
Agent: [K+]
Agent: [OH-]
Product: COCCNCc1ccnc2[nH]c(-c3cn(C)c4cc(OC)c(OC)cc34)cc12
Yield: 93.9 %

Procedure:
[2-(5,6-Dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl](2-methoxyethyl)amine is prepared as described in Example 179a starting with 0.12 g of [2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl](2-methoxyethyl)amine instead of the [2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl](4-trifluoromethylsulfanylbenzyl)amine used in Example 179a and 0.99 cm3 of 5N potassium hydroxide. 0.081 g of [2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl](2-methoxyethyl)amine is obtained, the characteristics of which are as follows:
Reaction SMILES: O.NN.[CH3:4][O:5][C:6]1[C:7]([N+:21]([O-])=O)=[C:8]([CH:18]=[CH:19][CH:20]=1)[C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[CH2:16][OH:17])=[O:10].[H][H]>[Ni].CO>[NH2:21][C:7]1[C:6]([O:5][CH3:4])=[CH:20][CH:19]=[CH:18][C:8]=1[C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[CH2:16][OH:17])=[O:10]
Reactant: [H][H]
Reactant: COc1cccc(C(=O)N2CCCC2CO)c1[N+](=O)[O-]
Agent: [Ni]
Agent: NN
Solvent: O
Solvent: CO
Product: COc1cccc(C(=O)N2CCCC2CO)c1N
Reaction time: 2 h
Yield: 96 %

Procedure:
Hydrazine hydrate (4.37 g, 136.4 mmol) was added dropwise to a solution of 92 (6.37 g, 22.7 mmol) in gently refluxing methanol (100 mL) over Raney nickel (2.4 g, slurry). The resulting vigorous evolution of hydrogen gas subsided after approximately 10 minutes and the reaction was deemed to be complete by TLC after 2 h. The reaction mixture was filtered through celite and the solvent evaporated. Distilled water (100 mL) was added to the residue, and the aqueous mixture was extracted with EtOAc (3×100 mL) and washed with H2O (3×100 mL) and brine (3×100 mL) and dried over anhydrous MgSO4. Evaporation of the solvent afforded a brown glass (5.49 g, 21.8 mmol) as a single spot by TLC.
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][S:5](=[O:38])([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[N:6][C:7](=[O:31])[C:8]1[CH:13]=[C:12]([C:14]#[C:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([NH:22][C:23]([C:25]3[O:26][CH:27]=[CH:28][C:29]=3[CH3:30])=[O:24])[CH:17]=2)[CH:11]=[N:10][CH:9]=1.C(Br)(Br)(Br)[Br:40].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Br:40][CH2:2][CH2:3][CH2:4][S@:5](=[O:38])([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[N:6][C:7](=[O:31])[C:8]1[CH:13]=[C:12]([C:14]#[C:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([NH:22][C:23]([C:25]3[O:26][CH:27]=[CH:28][C:29]=3[CH3:30])=[O:24])[CH:17]=2)[CH:11]=[N:10][CH:9]=1
Reactant: BrC(Br)(Br)Br
Reactant: Cc1ccoc1C(=O)Nc1cccc(C#Cc2cncc(C(=O)N=S(=O)(CCCO)c3ccccc3)c2)c1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: Cc1ccoc1C(=O)Nc1cccc(C#Cc2cncc(C(=O)N=[S@](=O)(CCCBr)c3ccccc3)c2)c1
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
N-[(3-hydroxypropyl)(oxido)phenyl--sulfanylidene]-5-({3-[(3-methyl-2-furoyl)amino]phenyl}ethynyl)nicotinamide (1.71 g, 3.24 mmol) was dissolved in anhydrous CH2Cl2 (5 mL) and the resulting solution was cooled to 0° C. A solution of carbon tetrabromide (1.565 g ) in CH2Cl2 (3 mL) was added dropwise followed by a dropwise addition of a solution of triphenylphosphine (1.24 g) in CH2Cl2 (3 mL). The reaction was stirred at room temperature for 1.5 hours and then partitioned between saturated aqueous NaHCO3 and dichloromethane. The organic layer was separated, washed with brine (1×), dried with anhydrous Na2SO4, and concentrated with silica gel under reduced pressure. A gradient column chromatography (acetone-hex: from 1:10 to 1:4) rendered title compound as white solid in amount of 1.56 g (82%).
Reaction SMILES: Br[C:2]1[C:11](=[S:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[O:4][CH:3]=1.[NH:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[NH:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[C:14]1[C:3]1[O:4][C:5]2[C:10]([C:11](=[S:12])[CH:2]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2
Reactant: S=c1c(Br)coc2ccccc12
Reactant: c1ccc2[nH]ccc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: S=c1cc(-c2cc3ccccc3[nH]2)oc2ccccc12
Temperature: 0 °C
Yield: 85.1 %

Procedure:
To an eggplant type flask (25 ml), 3-bromothiochromone (121 mg) prepared in Example 8, indole (234 mg), potassium carbonate (1382 mg), and dimethylformamide (15 ml) were added. The mixture was reacted at 80° C. for 20 hours with stirring. The reaction mixture was added to ice water and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purifiedby the silica gel colunm chromatography and recrystallized from benzene/hexane to give the titled compound (118.5 mg; yield=40.4%) as crystals. Melting point: 155°-156° C. 1H-NMR(CDCl3, δ ppm): 7.22 (s, H3), 8.57 (d, H5), 7.55-7.72 (m, H6), 7.55-7.72 (m, H7), 7.55-7.72 (m, H8), 7.45 (d, H2'), 6.79 (d, H3'), 7.60-7.70 (m, H4'), 7.22-7.38 (m, H5'), 7.22-7.38 (m, H6'), 7.88 (d, H7').