Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([BH3-])#N.[Na+].[NH2:5][CH2:6][CH2:7][CH2:8][P:9]([CH2:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)(=[O:11])[OH:10].[Cl:19][C:20]1[CH:21]=[C:22]([CH:25]=[C:26]([Cl:28])[CH:27]=1)[CH:23]=O.C(O)(=O)C>CO>[Cl:19][C:20]1[CH:21]=[C:22]([CH:25]=[C:26]([Cl:28])[CH:27]=1)[CH2:23][NH:5][CH2:6][CH2:7][CH2:8][P:9]([CH2:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)(=[O:10])[OH:11]
Reactant: NCCCP(=O)(O)CC1CCCCC1
Reactant: O=Cc1cc(Cl)cc(Cl)c1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: O=P(O)(CCCNCc1cc(Cl)cc(Cl)c1)CC1CCCCC1
Temperature: 25 °C
Reaction time: 96 h

Procedure:
2.0 g of sodium cyanoborohydride are added in portions to a solution of 6.27 g of 3-aminopropyl-(cyclohexylmethyl)-phosphinic acid and 5.0 g of 3,5-dichlorobenzaldehyde and 1.91 g of glacial acetic acid in 50 ml of anhydrous methanol and the mixture is stirred at room temperature for 4 days. The solvent is removed, the white residue is taken up in 2.0M hydrochloric acid and filtered. The filtrate is concentrated to dryness by evaporation and the white solid that remains behind is suspended in ethyl acetate, filtered off and crystallised from propanol, yielding 3-[(3,5-dichlorobenzyl)amino]-propyl-(cyclohexylmethyl)-phosphinic acid, m.p. 231°-233°.
Reaction SMILES: [Br-].[O:2]([CH2:9][CH2:10][CH2:11][CH2:12][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C([Li])CCC.[CH:37]([C:39]1[CH:51]=[CH:50][C:42]([CH:43]=[CH:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])=[CH:41][CH:40]=1)=O>C1COCC1>[O:2]([CH2:9][CH2:10][CH2:11][CH:12]=[CH:37][C:39]1[CH:40]=[CH:41][C:42](/[CH:43]=[CH:44]/[C:45]([O:47][CH2:48][CH3:49])=[O:46])=[CH:50][CH:51]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: c1ccc(OCCCC[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reactant: CCOC(=O)C=Cc1ccc(C=O)cc1
Agent: [Br-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCOC(=O)/C=C/c1ccc(C=CCCCOc2ccccc2)cc1
Temperature: -40 °C
Yield: 65 %

Procedure:
3.16 g of (4-phenoxybutyl)(triphenyl)phosphonium bromide are suspended in 25 ml of THF under argon and cooled to −40° C. 2.36 ml of n-butyllithium (1.6 molar in hexane) are added dropwise, and the mixture is warmed to 0° C. after 5 minutes and cooled again to −40° C. after 15 minutes. A solution of 0.70 g of ethyl 4-formylcinnamate in THF is added dropwise and, after 5 minutes, the reaction mixture is warmed to room temperature. The solvent is removed in a rotary evaporator. 0.75 g of product is obtained as an E/Z mixture.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][NH2:25])=[CH:19][CH:18]=1>>[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][NH:25][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[CH:4][C:3]=2[N+:12]([O-:14])=[O:13])=[CH:19][CH:18]=1
Reactant: O=[N+]([O-])c1cnc2ccccc2c1Cl
Reactant: COc1ccc(CCN)cc1
Product: COc1ccc(CCNc2c([N+](=O)[O-])cnc3ccccc23)cc1

Procedure:
Using the method of Example 1, 4-chloro-3-nitroquinoline was reacted with 2-(4-methoxyphenyl)ethylamine to provide 4-[2-(4-methoxyphenyl)ethylamino]-3-nitroquinoline.
Reaction SMILES: C(O[C:6]([C:8]1[N:9]=[C:10]([Cl:23])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][CH:20]([CH3:22])[CH3:21])[CH:12]=2)=[O:7])CCC.[CH3:24][N:25]([CH3:29])[CH2:26][CH2:27][NH2:28]>>[CH3:24][N:25]([CH3:29])[CH2:26][CH2:27][NH:28][C:6]([C:8]1[N:9]=[C:10]([Cl:23])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][CH:20]([CH3:21])[CH3:22])[CH:12]=2)=[O:7]
Reactant: CCCCOC(=O)c1nc(Cl)c2cc(OC(C)C)ccc2c1O
Reactant: CN(C)CCN
Product: CC(C)Oc1ccc2c(O)c(C(=O)NCCN(C)C)nc(Cl)c2c1

Procedure:
Synthesized from 1-chloro-4-hydroxy-7-isopropoxy-isoquinoline-3-carboxylic acid butyl ester (can be obtained according to U.S. Pat. No. 6,093,730, October 1998, Weidmann et al.) and N,N-dimethyl-ethane-1,2-diamine in analogy to example B-4, followed by deprotection in analogy to example B-1 f); MS-(+)-ion: M+1=352.1.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Br:25][C:26]1[C:31]([NH2:32])=[C:30]2[O:33][CH2:34][O:35][C:29]2=[CH:28][CH:27]=1>>[Br:25][C:26]1[C:31]([NH:32][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[C:30]2[O:33][CH2:34][O:35][C:29]2=[CH:28][CH:27]=1
Reactant: Nc1c(Br)ccc2c1OCO2
Reactant: COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1
Product: COc1cc2c(Nc3c(Br)ccc4c3OCO4)ncnc2cc1OCCCN1CCN(C)CC1

Procedure:
Using an analogous procedure to that described in Example 15, 4-chloro-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazoline was reacted with 6-bromo-2,3-Methylenedioxyaniline to give the title compound as a solid; NMR Spectrum: DMSOd6 and CF3CO2D) 2.3 (m, 2H), 2.95 (s, 3H), 3.2–3.9 (br s, 8H), 3.4 (m, 2H), 4.0 (s, 3H), 4.35 (m, 2H), 6.15 (s, 2H), 7.05 (d, 1H), 7.3 (d, 1H), 7.4 (s, 1H), 8.15 (s, 1H), 8.9 (s, 1H); Mass Spectrum: M+H+ 530 and 532; Elemental Analysis: Found C, 54.25; H, 5.54; N, 12.8. C24H28BrN5O4 requires C, 54.35; H, 5.32; N, 13.2%.
Reaction SMILES: [CH2:1]([N:3](CC)CC)C.CN.Cl[C:11]1[CH:27]=[CH:26][C:14]([C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[O:16])=[CH:13][N:12]=1>CO>[CH3:1][NH:3][C:11]1[CH:27]=[CH:26][C:14]([C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[O:16])=[CH:13][N:12]=1
Reactant: COc1ccc(NC(=O)c2ccc(Cl)nc2)cc1
Reactant: CCN(CC)CC
Agent: CN
Solvent: CO
Product: CNc1ccc(C(=O)Nc2ccc(OC)cc2)cn1
Temperature: 100 °C
Reaction time: 8 h
Yield: 89.9 %

Procedure:
Methanol (20 mL), triethylamine (1.59 mL, 11.4 mmol) and monomethylamine (2.0 M in MeOH, 19 mL, 38.0 mmol) were added to a pressure tube containing 6-chloro-N-(4-methoxyphenyl)nicotinamide (37, 2.0 g, 7.61 mmol) obtained in step 1. After agitating at 100° C. overnight and then cooling to room temperature, the product was removed by filtration. Removal of the solvent under reduced pressure yielded the target compound 6-(N-monomethylamino)-N-(4-methoxyphenyl)nicotinamide (38, 1.76 g, 90%) without further purification.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[CH:8][C:7]=2/[CH:14]=[CH:15]/[C:16]2[N:17]=[C:18]3[N:22]([C:23]=2[C:24]([OH:26])=O)[CH:21]=[CH:20][S:19]3)[CH2:3][CH2:2]1.[NH:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][CH2:29][CH2:28]1.C(N(CC)CC)C>ClCCl>[CH:1]1([CH2:4][O:5][C:6]2[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[CH:8][C:7]=2/[CH:14]=[CH:15]/[C:16]2[N:17]=[C:18]3[N:22]([C:23]=2[C:24]([N:27]2[C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[CH2:30][CH2:29][CH2:28]2)=[O:26])[CH:21]=[CH:20][S:19]3)[CH2:2][CH2:3]1
Reactant: COc1cccc(/C=C/c2nc3sccn3c2C(=O)O)c1OCC1CC1
Reactant: c1ccc2c(c1)CCCN2
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cccc(/C=C/c2nc3sccn3c2C(=O)N2CCCc3ccccc32)c1OCC1CC1

Procedure:
The title compound was prepared according to the general procedure (Method A) by coupling Intermediate 1 (100 mg, 0.269 mmol) with 1,2,3,4-tetrahydroquinoline (39 μL, 0.296 mmol) in the presence of triethylamine (68 mg, 0.674 mmol) in dichloromethane (5 mL) gave 79 mg of the product as an off-white solid; 1H NMR (300 MHz, DMSO-d6) δ 0.21-0.22 (m, 2H), 0.45-0.47 (m, 2H), 1.09-1.11 (m, 1H), 1.97-2.00 (m, 2H), 2.85-2.87 (m, 2H), 3.66 (d, J=6.6 Hz, 2H), 3.76 (s, 3H), 3.83-3.85 (m, 2H), 6.75 (d, J=16.2 Hz, 1H), 6.85-6.93 (m, 4H), 6.98-7.03 (m, 2H), 7.13-7.15 (m, 1H), 7.26 (d, J=4.2 Hz, 1H), 7.56 (s, 1H), 7.61-7.64 (m, 1H); ESI-MS (m/z) 486.45 (MH)+.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[NH:11][CH2:12][C:13]([C:28]([F:31])([F:30])[F:29])([OH:27])[CH2:14][C:15]([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=2[O:25]C)([CH3:17])[CH3:16])[CH:4]=[CH:3][CH:2]=1.B(Br)(Br)Br.C(Cl)Cl.C([O-])(O)=O.[Na+]>C(Cl)Cl>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[NH:11][CH2:12][C:13]([C:28]([F:31])([F:29])[F:30])([OH:27])[CH2:14][C:15]([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=2[OH:25])([CH3:17])[CH3:16])[CH:4]=[CH:3][CH:2]=1
Reactant: COc1ccc(F)cc1C(C)(C)CC(O)(CNc1cccc2cccnc12)C(F)(F)F
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(CC(O)(CNc1cccc2cccnc12)C(F)(F)F)c1cc(F)ccc1O
Reaction time: 20 h
Yield: 97.8 %

Procedure:
200 mg (0.46 mmol) of 1-(quinolin-8-ylamino)-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-(trifluoromethyl)pentan-2-ol in 20 ml of CH2Cl2 is mixed at 0° C. with 9 ml of 1 M boron tribromide-CH2Cl2 solution. After 20 hours at room temperature, the batch is poured into saturated NaHCO3 solution, stirred for 20 minutes and extracted with CH2Cl2. The combined organic extracts are washed with water, dried (Na2SO4) and concentrated by evaporation in a vacuum. Chromatography with hexane-ethyl acetate (0–25%) on silica gel yields 190 mg of the product.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[NH:14][CH2:15][CH2:16][CH2:17][CH2:18][OH:19])=[CH:11][CH:10]=[CH:9][CH:8]=2)([O-])=O.[H][H].C(O)C>C1(C)C=CC=CC=1.[Pd]>[NH2:1][C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[NH:14][CH2:15][CH2:16][CH2:17][CH2:18][OH:19])=[CH:11][CH:10]=[CH:9][CH:8]=2
Reactant: O=[N+]([O-])c1cnc2ccccc2c1NCCCCO
Reactant: [H][H]
Agent: [Pd]
Solvent: Cc1ccccc1
Solvent: CCO
Product: Nc1cnc2ccccc2c1NCCCCO
Reaction time: 1 h
Yield: 105.6 %

Procedure:
Catalyst (5% Pd/C) was added to a suspension of 4-[(3-nitroquinolin-4-yl)amino]butan-1-ol (18.2 g, 69.6 mmol) in toluene (450 mL) in a Parr vessel. The vessel was placed on a shaker and pressurized with hydrogen. The next day ethanol (60 mL) and additional catalyst were added and the vessel was again pressurized with hydrogen. After 1 hour analysis by TLC indicated that all of the starting material had been consumed. The reaction mixture was filtered through a layer of CELITE filter aid and then concentrated under reduced pressure to provide 17 g of 4-[(3-aminoquinolin-4-yl)amino]butan-1-ol.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.CC(C)([O-])C.[K+].Cl[C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[N:21][CH:22]=2)[CH:17]=[CH:16][N:15]=1>C(O)(C)(C)C>[N:1]1([C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[N:21][CH:22]=3)[CH:17]=[CH:16][N:15]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1
Reactant: Clc1nccc2ccncc12
Reactant: C1CNCCN1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(C)(C)O
Product: c1cc2ccnc(N3CCNCC3)c2cn1
Reaction time: 8 h
Yield: 63.9 %

Procedure:
A solution of piperazine (5.5 g, 64 mmol) in t-butanol (50 mL) was treated with potassium t-butoxide (0.9 g, 8 mmol) in one portion. After stirring for 10 minutes at 40° C. a solution of 1-chloro-2,7-naphthyridine (1.2 g, 7.3 mmol) in 10 mL of t-butanol was added. Stirring was continued overnight at 40° C. after which the solvent was removed in vacuo. The residue was purified by flash chromatography (silica gel 60 Merck, methylene chloride-methanol-ammonia 9:1:0.125) to give the product (1.0 g, 64%) as a yellow solid.
Reaction SMILES: [NH2:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([Br:9])=[CH:4][C:3]=1[C:10](=O)[CH3:11].OS(O)(=O)=O.[N:18]([O-])=O.[Na+].O.O.Cl[Sn]Cl>O>[Br:9][C:5]1[CH:4]=[C:3]2[C:2](=[C:7]([Cl:8])[CH:6]=1)[NH:1][N:18]=[C:10]2[CH3:11]
Reactant: O=N[O-]
Reactant: CC(=O)c1cc(Br)cc(Cl)c1N
Agent: Cl[Sn]Cl
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Product: Cc1n[nH]c2c(Cl)cc(Br)cc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 63.8 %

Procedure:
To a 0° C. solution of 1-(2-amino-5-bromo-3-chlorophenyl)ethanone (206 mg, 0.83 mmol) in 50% aqueous solution of concentrated H2SO4 was slowly added NaNO2 (73 mg, 1.0 mmol). The cooling bath was removed following the addition of NaNO2, stirred at room temperature for 1 hour and then recooled to 0° C. before addition of SnCl2.2H2O (573 mg, 2.49 mmol). The mixture was stirred at 0° C. for 1 hour before dilution with water. The solids were collected by vacuum filtration to afford 5-bromo-7-chloro-3-methyl-1H-indazole (130 mg, 64%).
Reaction SMILES: [N:1]1([C@H:6]2[CH2:10][CH2:9][CH2:8][C@H:7]2[NH2:11])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:12]([C:14]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([O:27][CH3:28])[C:15]=1[C:16](O)=[O:17])[CH3:13]>>[CH2:12]([C:14]1[CH:22]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:20]=[C:19]([O:27][CH3:28])[C:15]=1[C:16]([NH:11][C@@H:7]1[CH2:8][CH2:9][CH2:10][C@@H:6]1[N:1]1[CH2:2][CH2:3][CH2:4][CH2:5]1)=[O:17])[CH3:13]
Reactant: N[C@@H]1CCC[C@@H]1N1CCCC1
Reactant: CCc1cc(C(F)(F)F)cc(OC)c1C(=O)O
Product: CCc1cc(C(F)(F)F)cc(OC)c1C(=O)N[C@@H]1CCC[C@@H]1N1CCCC1

Procedure:
The title compound, light yellow oil, MS: m/e=385.2 [(M+H)+], was prepared in accordance with the general method of example 5 from cis-2-pyrrolidin-1-yl-cyclopentylamine (intermediate Q) and 2-ethyl-6-methoxy-4-trifluoromethyl-benzoic acid (intermediate AR).
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([Br:12])[N:7]=1)=[O:5].[CH3:13][O:14][C:15]([C@H:17]1[CH2:22][CH2:21][C@H:20]([C:23](Cl)=[O:24])[CH2:19][CH2:18]1)=[O:16].C(N(CC)CC)C>C(#N)C>[CH3:13][O:14][C:15]([C@H:17]1[CH2:22][CH2:21][C@H:20]([C:23](=[O:24])[NH:2][CH2:3][C:4]([C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([Br:12])[N:7]=2)=[O:5])[CH2:19][CH2:18]1)=[O:16]
Reactant: NCC(=O)c1cccc(Br)n1
Reactant: COC(=O)[C@H]1CC[C@H](C(=O)Cl)CC1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CC#N
Product: COC(=O)[C@H]1CC[C@H](C(=O)NCC(=O)c2cccc(Br)n2)CC1

Procedure:
To a suspension of 2-amino-1-(6-bromopyridin-2-yl)ethanone hydrochloride (10.00 g, 39.8 mmol) obtained in Step 1, trans-4-chlorocarbonylcyclohexanecarboxylic acid methyl ester (9.00 g, 44.0 mmol) in acetonitrile (200 ml), a solution of triethylamine (13.9 ml, 100 mmol) in acetonitrile (60 ml) was added dropwise while ice-cooled for 2 hours. After the reaction solution was concentrated, water was added and extracted with ethyl acetate. The organic layer was sequentially washed with 10% aqueous citric acid, a saturated aqueous sodium bicarbonate, a saturated brine and dried over magnesium sulfate. After concentrated, the residue was purified by flash chromatography on silica gel (n-hexane:ethyl acetate=1:2) and the title compound (7.38 g, 48%) was obtained.
Reaction SMILES: [CH:1]1([C:4]2[N:14]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[C:28]#[N:29])=[CH:18][CH:17]=3)[C:7]3=[N:8][CH:9]=[C:10](Br)[C:11]([CH3:12])=[C:6]3[N:5]=2)[CH2:3][CH2:2]1.C(O)=O>[Pd].C1(C)C=CC=CC=1>[CH:1]1([C:4]2[N:14]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[C:28]#[N:29])=[CH:18][CH:17]=3)[C:7]3=[N:8][CH:9]=[CH:10][C:11]([CH3:12])=[C:6]3[N:5]=2)[CH2:3][CH2:2]1
Reactant: Cc1c(Br)cnc2c1nc(C1CC1)n2Cc1ccc(-c2ccccc2C#N)cc1
Agent: [Pd]
Solvent: O=CO
Solvent: Cc1ccccc1
Product: Cc1ccnc2c1nc(C1CC1)n2Cc1ccc(-c2ccccc2C#N)cc1
Yield: 78 %

Procedure:
Toluene (30 ml) was added to 2.0 g (4.5 mmol) of 2-cyclopropyl-3-(2'-cyanobiphenyl-4-yl)methyl-6-bromo-7-methyl-3H-imidazo[4,5-b]pyridine, 1.24 g (27.0 mmol) of formic acid, 4.55 g (45.0 mmol) of rriethylamine and 10% Pd-C (100 mg), followed by heating under reflux for 6 hours. After the reaction liquid was brought to room temperature and filtered to remove the catalyst, vacuum concentration was effected. Chloroform (50 ml) and water (50 ml) were added to the residue and the obtained mixture was caused liquid-liquid separation. The aqueous phase was further extracted with chloroform (30 ml) twice. The organic phases were combined, dried over anhydrous magnesium sulfate and subjected to vacuum concentration. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to give 1.28 g of 2-cyclopropyl-3-(2'-cyanobiphenyl-4-yl)methyl-7-methyl-3H-imidazo[4,5-b]pyridine (yield 78%).
Reaction SMILES: C([O:4][C@H:5]1[CH:10]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH2:9][C@H:8]2[C@H:17]3[C@H:27]([CH2:28][CH2:29][C@:6]12[CH3:7])[C@:25]1([CH3:26])[C@H:20]([CH2:21][C@@H:22]([CH3:31])[C:23](=O)[CH2:24]1)[CH2:19][CH2:18]3)(=O)C.[NH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1>C(O)=O>[CH3:31][C@H:22]1[C@@H:23]([N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH2:24][C@@:25]2([CH3:26])[C@@H:20]([CH2:19][CH2:18][C@@H:17]3[C@@H:27]2[CH2:28][CH2:29][C@@:6]2([CH3:7])[C@H:8]3[CH2:9][C@H:10]([N:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)[C@@H:5]2[OH:4])[CH2:21]1
Reactant: C1CCNCC1
Reactant: CC(=O)O[C@H]1C(N2CCCCC2)C[C@H]2[C@@H]3CC[C@H]4C[C@@H](C)C(=O)C[C@]4(C)[C@H]3CC[C@]12C
Solvent: O=CO
Product: C[C@@H]1C[C@@H]2CC[C@@H]3[C@H](CC[C@]4(C)[C@@H](O)[C@@H](N5CCCCC5)C[C@@H]34)[C@@]2(C)C[C@@H]1N1CCCCC1

Procedure:
17β-Acetyloxy-3β-methyl-16-(1-piperidinyl)-5α-androstan-2-one was treated with piperidine and formic acid, as described in Example I(h), to give 3β-methyl-2β,16β-di-(1-piperidinyl)-5α-androstan-17β-ol.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:6](=[O:17])[S:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10](Br)[CH:9]=2)=[O:4].[N:18]1[CH:23]=[CH:22][CH:21]=[C:20](B(O)O)[CH:19]=1>>[CH3:1][O:2][C:3]([C:5]1[C:6](=[O:17])[S:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([C:20]1[CH:19]=[N:18][CH:23]=[CH:22][CH:21]=1)[CH:9]=2)=[O:4]
Reactant: COC(=O)c1c(O)c2ccc(Br)cc2sc1=O
Reactant: OB(O)c1cccnc1
Product: COC(=O)c1c(O)c2ccc(-c3cccnc3)cc2sc1=O

Procedure:
4-Hydroxy-2-oxo-7-pyridin-3-yl-2H-thiochromene-3-carboxylic acid methyl ester was prepared from 7-bromo-4-hydroxy-2-oxo-2H-thiochromene-3-carboxylic acid methyl ester (Example 5 e) and 3-pyridyl-boronic acid under conditions analogous to Example 14(a). MS ESI(+) m/e: 314.12 (M+1).
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.[C:11]([C:13]1([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([O:31][CH:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)[CH:24]=2)[CH2:18][CH2:17][C:16]2([O:22][CH2:21][CH2:20][O:19]2)[CH2:15][CH2:14]1)#N.S(=O)(O)[O-:38].[Na+]>C1(C)C=CC=CC=1>[CH:32]1([O:31][C:25]2[CH:24]=[C:23]([C:13]3([CH:11]=[O:38])[CH2:18][CH2:17][C:16]4([O:19][CH2:20][CH2:21][O:22]4)[CH2:15][CH2:14]3)[CH:28]=[CH:27][C:26]=2[O:29][CH3:30])[CH2:36][CH2:35][CH2:34][CH2:33]1
Reactant: O=S([O-])O
Reactant: COc1ccc(C2(C#N)CCC3(CC2)OCCO3)cc1OC1CCCC1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COc1ccc(C2(C=O)CCC3(CC2)OCCO3)cc1OC1CCCC1
Reaction time: 18 h

Procedure:
Diisobutylaluminum hydride (1.0M in toluene, 8.13 mL, 8.13 mmol) was added dropwise to a solution of 4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)-1,1-(ethylenedioxy)cyclohexane (1.16 g, 3.19 mmol) dissolved in toluene (20 mL) under an argon atmosphere. After 18 h at room temperature, saturated aqueous sodium bisulfite (100 mL) was added and the mixture was extracted three times with dichloromethane. The combined organic extract was washed with brine, was dried (potassium carbonate) and was evaporated. Purification by flash chromatography, eluting with 4:1 hexanes/ethyl acetate, provided a clear colorless oil. 1H NMR(400 MHz, CDCl3) δ 9.35 (s, 1H), 6.88 (br s, 2H), 6.80 (s, 1H), 4.73 (m, 1H), 3.95 (m, 4H), 3.85 (s, 3H), 2.33 (m, 2H), 2.10 (m, 2H), 1.57-1.99 (m, 12H).
Reaction SMILES: [OH:1][C:2]1[C:7]([NH:8][C:9]([C:11]2[O:12][CH:13]=[CH:14][CH:15]=2)=[O:10])=[C:6]([OH:16])[N:5]=[C:4](SC)[N:3]=1.[CH3:19][O:20][C:21]1[CH:29]=[CH:28][C:24]([CH2:25][CH2:26][NH2:27])=[CH:23][CH:22]=1.Cl>O>[OH:1][C:2]1[C:7]([NH:8][C:9]([C:11]2[O:12][CH:13]=[CH:14][CH:15]=2)=[O:10])=[C:6]([OH:16])[N:5]=[C:4]([NH:27][CH2:26][CH2:25][C:24]2[CH:28]=[CH:29][C:21]([O:20][CH3:19])=[CH:22][CH:23]=2)[N:3]=1
Reactant: CSc1nc(O)c(NC(=O)c2ccco2)c(O)n1
Reactant: COc1ccc(CCN)cc1
Agent: Cl
Solvent: O
Product: COc1ccc(CCNc2nc(O)c(NC(=O)c3ccco3)c(O)n2)cc1
Temperature: 90 °C
Yield: 16.6 %

Procedure:
A mixture of 4,6-dihydroxy-5-(2-furanylcarbonyl)amino-2-methylthiopyrimidine (2 g, 7.5 mM), p-methoxyphenethylamine (3.4 g, 22.5 mH), and water (25 ml) was heated at 90° C. for 15 hours. The mixture was then poured into water (100 ml) and acidified with concentrated hydrochloric acid until PH<3. The resultant precipitate was removed by filtration and recrystallised from methanol/water (3:1) to afford 4,6-dihydroxy-5-(2-furanylcarbonyl)amino-2-[(4-methoxy-phenyl)ethyl]aminopyrimidine as a white solid (0.46 g, 16.6% yield) m.p >250° C.; NMR: DMSO-d6 : 2.75(t,2H,ArCH2), 3.47(brq,2H,CH2NH), 3.73 (s,3H, OMe), 6.50(brs, 1H, NH), 6.61(m, 1H,furyl-H), 6.87(d,2H,ArH), 7.16(d,2H,ArH), 7.17(s,1H furyl-H), 7.82(d,1H,furyl-H), 8.64(brs,1H,NHCO), 10.58(brs,2H,OH ×2); m/e [M+H]+ , 371:
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].[C:13](=O)([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[O:14]C(Cl)C>C1COCC1>[C:19]([O:18][C:13]([N:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)=[O:14])([CH3:22])([CH3:21])[CH3:20]
Reactant: CC(Cl)OC(=O)OC(C)(C)C
Reactant: C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCCCC1

Procedure:
The procedure is as in Example 7, but with 8.5 g (0.1 mole) of piperidine, 60 ml of THF, 20 ml of saturated aqueous K2CO3 solution and 0.11 mole of α-chloroethyl tert-butyl carbonate.
Reaction SMILES: [CH3:1][C:2]1([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:7][CH2:6][C:5](=O)[CH2:4][CH2:3]1.CO.C([O-])=O.[NH4+:22]>[Pd].O>[NH2:22][CH:5]1[CH2:6][CH2:7][C:2]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:1])[CH2:3][CH2:4]1
Reactant: [NH4+]
Reactant: CC1(NC(=O)OC(C)(C)C)CCC(=O)CC1
Agent: [Pd]
Agent: O=C[O-]
Solvent: O
Solvent: CO
Product: CC1(NC(=O)OC(C)(C)C)CCC(N)CC1
Reaction time: 1 h
Yield: 92.8 %

Procedure:
To a mixture of tert-butyl (1-methyl-4-oxocyclohexyl)carbamate (4.00 g) and methanol (50 mL), ammonium formate (10.2 g) and water (5 mL) were added and stirred for 1 hour until they were completely dissolved. Then, 10% palladium on carbon (2.0 g) was added and stirred at room temperature for 65 hours. After insoluble materials were separated by filtration through celite, the solvent was distilled off, and chloroform was added to the resulting residue, followed by drying over anhydrous magnesium sulfate. The solvent was distilled off to give tert-butyl (4-amino-1-methylcyclohexyl)carbamate (3.73 g) as a colorless syrup.
Reaction SMILES: [C:1]([C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]=1[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][C:14]=1[P:23]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:24])#[N:2].OO.C(=O)([O-])[O-:40].[K+].[K+]>CS(C)=O.O>[C:1]([C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]=1[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][C:14]=1[P:23]([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:24])(=[O:40])[NH2:2]
Reactant: N#Cc1ccc2ccccc2c1-c1c(P(=O)(c2ccccc2)c2ccccc2)ccc2ccccc12
Reactant: O=C([O-])[O-]
Agent: OO
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: NC(=O)c1ccc2ccccc2c1-c1c(P(=O)(c2ccccc2)c2ccccc2)ccc2ccccc12
Reaction time: 15 h
Yield: 98.6 %

Procedure:
9.99 g (20.8 mmol) of (+)-2-cyano-2′-diphenylphosphinyl-1,1′-binaphthyl (the formula (4a)), synthesized according to the known method (Tetrahedron 50, 4293, (1994)), was weighed and added into a four neck flask, which was equipped with a thermometer, a cooling tube and a dropping funnel with an equalizer. 100 ml of Dimethylsulfoxide was added into the flask. 50 ml of 30 percent aqueous solution of hydrogen peroxide was added at 0° C. followed by the addition of potassium carbonate (57.6 g) and sonication for 25 minutes. Thereafter, 43 ml of water was added and 43 ml of dimethylsulfoxide was then added, followed by sonication to the resultant mixture for 30 minutes, which was then stirred for 15 hours. The resultant mixture was extracted with 300 ml of ethyl acetate, and the extract was washed with 100 ml of saturated aqueous solution of ammonium chloride and 200 ml of brine, and then dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure and the residue was purified using a silica gel column chromatography (eluent: ethyl acetate) to obtain 10.2 gram of the titled compound.