Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[C:4]2[N:5]([CH:21]=[N:22][N:23]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][CH:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:11][CH2:10]1)#[N:2].O(Cl)Cl.[P+5].CN([CH:31]=[O:32])C>>[C:1]([C:3]1[C:4]2[N:5]([C:21]([CH:31]=[O:32])=[N:22][N:23]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][CH:12]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:11][CH2:10]1)#[N:2]
Reactant: N#Cc1c(N2CCC(c3ccccc3)CC2)ccn2cnnc12
Reactant: CN(C)C=O
Agent: ClOCl
Agent: [P+5]
Product: N#Cc1c(N2CCC(c3ccccc3)CC2)ccn2c(C=O)nnc12
Yield: 26 %

Procedure:
D8 (0.25 g, 0.824 mmol) and phosphorus(V)oxychloride (0.116 ml, 1.236 mmol) in DMF (5 ml) was heated in a sealed tube at 80° C. for 4 h. After cooling, the mixture was concentrated in vacuo. The crude product was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH up to 3% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D9 (0.070 g, 26%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[C@@H:4]([O:14][CH2:15][CH3:16])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:7]=1[Cl:13].Cl[CH2:19][C:20]1[N:21]=[C:22]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[C:28]([CH3:33])[CH:27]=2)[O:23][C:24]=1[CH3:25].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+]>>[CH3:1][O:2][C:3](=[O:17])[C@@H:4]([O:14][CH2:15][CH3:16])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:19][C:20]2[N:21]=[C:22]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[C:28]([CH3:33])[CH:27]=3)[O:23][C:24]=2[CH3:25])=[CH:8][C:7]=1[Cl:13]
Reactant: CCO[C@@H](Cc1ccc(O)cc1Cl)C(=O)OC
Reactant: Cc1cc(-c2nc(CCl)c(C)o2)ccc1F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [I-]
Product: CCO[C@@H](Cc1ccc(OCc2nc(-c3ccc(F)c(C)c3)oc2C)cc1Cl)C(=O)OC

Procedure:
In analogy to the procedure described in example 1 f], (2S)-3-(2-chloro-4-hydroxy-phenyl)-2-ethoxy-propionic acid methyl ester (example 15 d]) was reacted with 4-chloromethyl-2-(4-fluoro-3-methyl-phenyl)-5-methyl-oxazole (example 5 b]) in the presence of cesium carbonate and potassium iodide to yield (S)-3-{2-chloro-4-[2-(4-fluoro-3-methyl-phenyl)-5-methyl-oxazol-4-ylmethoxy]-phenyl}-2-ethoxy-propionic acid methyl ester as colorless liquid.
Reaction SMILES: [CH3:1][CH:2]([CH3:14])[C:3]([O:5][CH:6]([O:8][C:9](SCC)=[O:10])[CH3:7])=[O:4].S(Cl)([Cl:18])(=O)=O>>[CH3:1][CH:2]([CH3:14])[C:3]([O:5][CH:6]([O:8][C:9]([Cl:18])=[O:10])[CH3:7])=[O:4]
Reactant: CCSC(=O)OC(C)OC(=O)C(C)C
Reactant: O=S(=O)(Cl)Cl
Product: CC(OC(=O)Cl)OC(=O)C(C)C
Reaction time: 0.75 h

Procedure:
1-{[(Ethylthio)carbonyl]oxy}ethyl 2-methylpropionate (WO2005/66122) (412 mg) was cooled to −30° C. Sulfuryl chloride (157 μl) was added thereto, and the mixture was then stirred for 45 minutes. The solvent in the reaction solution was distilled off under reduced pressure to obtain a crude product of the title compound.
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:17]([C:22]([O:24]C(C)(C)C)=[O:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:12][CH:11]=2)[C:7]2[CH:29]=[CH:30][CH:31]=[CH:32][C:6]=2[N:5]=1.FC(F)(F)C(O)=O>>[CH3:1][O:2][CH2:3][C:4]1[N:8]([CH2:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3[C:17]([C:22]([OH:24])=[O:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:14][CH:15]=2)[C:7]2[CH:29]=[CH:30][CH:31]=[CH:32][C:6]=2[N:5]=1
Reactant: COCc1nc2ccccc2n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Solvent: O=C(O)C(F)(F)F
Product: COCc1nc2ccccc2n1Cc1ccc(-c2ccccc2C(=O)O)cc1

Procedure:
Prepared in analogous manner to Example 9 from tert.butyl 4'-[(2-methoxymethyl-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylate and trifluoroacetic acid.
Reaction SMILES: [CH:1]([C:4]1[CH:12]=[CH:11][C:10]2[NH:9][C:8]3[C:13]4[C:18]([CH2:19][C:7]=3[C:6]=2[CH:5]=1)=[CH:17][CH:16]=[CH:15][CH:14]=4)([CH3:3])[CH3:2].C([BH3-])#N.[Na+].[OH-].[Na+]>C(O)(=O)C>[CH:1]([C:4]1[CH:12]=[CH:11][C:10]2[NH:9][C@@H:8]3[C:13]4[C:18]([CH2:19][C@@H:7]3[C:6]=2[CH:5]=1)=[CH:17][CH:16]=[CH:15][CH:14]=4)([CH3:3])[CH3:2]
Reactant: CC(C)c1ccc2[nH]c3c(c2c1)Cc1ccccc1-3
Agent: [BH3-]C#N
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Product: CC(C)c1ccc2c(c1)[C@H]1Cc3ccccc3[C@H]1N2
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
5,10-Dihydro-8-iso-propylindeno [1,2-b]indole (5.27 g, 21.3 mmol) was stirred at room temperature in glacial acetic acid (100 cm3). Sodium cyanoborohydride (5 g, 3 equivalents) was added portionwise over a period of 30 minutes. The reaction was stirred for a further 30 minutes, and then poured into ice/water (150 cm3). After stirring for 30 minutes, the solution was neutralised with aqueous sodium hydroxide, and the colourless solid thus formed collected by filtration. This solid was washed copiously with water until the residue was free from cyanide ion and then dried in a vacuum oven to give the title compound as a colourless solid. Yield: 3.25 g (61%). M.p. 104° C. [from petrol (60°-80° C.)]. 1H NMR (CDCl3) δ: 1.19 (6H, d,), 2.80 (1H, septet,), 3.20 (1H, dd,), 3.48 (1H, dd,), 4.07 (1H, br,), 4.15 (1H, ddd,), 5.21 (1H, d,), 6.53 (1H, d,), 6.86 (1H, dd,), 7.03 (1H, s,), 7.1-7.4 (4H, m,).
Reaction SMILES: [OH:1][C@H:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:13])[C:3]([O:5][CH3:6])=[O:4].C(N(CC)CC)C.[N+:21]([C:24]1[CH:29]=[CH:28][C:27]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:25]=1)([O-:23])=[O:22].Cl>CN(C)C1C=CN=CC=1.ClCCl>[N+:21]([C:24]1[CH:25]=[CH:26][C:27]([S:30]([O:1][C@H:2]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[Cl:13])[C:3]([O:5][CH3:6])=[O:4])(=[O:32])=[O:31])=[CH:28][CH:29]=1)([O-:23])=[O:22]
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Cl)cc1
Reactant: COC(=O)[C@H](O)c1ccccc1Cl
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)[C@H](OS(=O)(=O)c1ccc([N+](=O)[O-])cc1)c1ccccc1Cl
Temperature: 0 °C
Reaction time: 3 h
Yield: 98 %

Procedure:
0.72 g (6 mmoles; 0.1 equivalent) of 4-dimethylaminopyridine, 12.0 g (60 mmoles; 1 equivalent) of methyl(R)-2-hydroxy-2(2-chlorophenyl)acetate and 7.8 g (78 mmoles; 1.3 equivalent) of triethylamine and 20 ml of dichloromethane were added to a dry reaction flask. The colorless solution obtained was cooled to 0° C. and then, operating at this temperature, 13.14 g (60 mmoles; 1 equivalent) of 4-nitrobenzenesulfonyl chloride as a solution in 30 ml of dichloromethane was added. The reaction mixture was stirred for 3 hours at 0° C. and 240 ml of 1N hydrochloric acid and 240 ml of dichloromethane was added drop wise, while stirring this mixture. After decanting, the dichloromethane phase is washed with dilute hydrochloric acid and then with water, before being concentrated under reduced pressure. An analytically pure sample is obtained after purifying on a silica column. In this manner, methyl(R)-2-(4-nitrophenylsulfonyloxy)-2(2-chlorophenyl)acetate is obtained: Yield: 98%. Optical purity: 99%.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:14]([NH:16][C:17]([C:19]2[N:20]=[C:21](Cl)[O:22][CH:23]=2)=[O:18])[CH3:15])[CH:5]=[C:6]([F:13])[C:7]=1[NH:8][S:9]([CH3:12])(=[O:11])=[O:10].[CH:25]1([C:29]2[CH:30]=[C:31]([OH:35])[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][CH2:26]1>>[F:1][C:2]1[CH:3]=[C:4]([CH:14]([NH:16][C:17]([C:19]2[N:20]=[C:21]([O:35][C:31]3[CH:32]=[CH:33][CH:34]=[C:29]([CH:25]4[CH2:28][CH2:27][CH2:26]4)[CH:30]=3)[O:22][CH:23]=2)=[O:18])[CH3:15])[CH:5]=[C:6]([F:13])[C:7]=1[NH:8][S:9]([CH3:12])(=[O:11])=[O:10]
Reactant: CC(NC(=O)c1coc(Cl)n1)c1cc(F)c(NS(C)(=O)=O)c(F)c1
Reactant: Oc1cccc(C2CCC2)c1
Product: CC(NC(=O)c1coc(Oc2cccc(C3CCC3)c2)n1)c1cc(F)c(NS(C)(=O)=O)c(F)c1
Yield: 98.6 %

Procedure:
2-Chloro-oxazole-4-carboxylic acid [1-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-amide (50 mg, 0.13 mmol) was reacted with 3-cyclobutyl-phenol (38.7 mg, 0.26 mmol) to give the title compound (63 mg, 98%) after purification by column chromatography (gradient 12% to 100% EtOAc in n-hexane).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[CH3:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=1)=O.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1(C)C=CC=CC=1>[F:30][C:29]([F:31])([F:32])[C:26]1[CH:25]=[CH:24][C:23]([C:21](=[N:1][C:2]2[CH:3]=[CH:4][C:5]([O:8][C:9]3[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=3)=[N:6][CH:7]=2)[CH3:20])=[CH:28][CH:27]=1
Reactant: CC(=O)c1ccc(C(F)(F)F)cc1
Reactant: CCOC(=O)c1ccc(Oc2ccc(N)cn2)cc1
Agent: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Solvent: Cc1ccccc1
Product: CCOC(=O)c1ccc(Oc2ccc(N=C(C)c3ccc(C(F)(F)F)cc3)cn2)cc1

Procedure:
Ethyl 4-(5-aminopyridin-2-yloxy)benzoate (16.0 g, 62 mmol) was dissolved in toluene (300 mL). To the resulting solution were added 4-trifluoromethylacetophenone (11.7 g, 62 mmol) and (±)-camphor-10-sulfonic acid (1.08 g, 4.65 mmol), and refluxed overnight. The reaction solution was concentrated under reduced pressure, to thereby yield 26.5 g of the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]([C:29]([O:31]C)=O)[C:12]3[NH:13][C:14]4[CH:15]=[C:16]([N:22]5[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]5)[CH:17]=[CH:18][C:19]=4[C:20]=3[N:21]=2)[CH:5]=[CH:6][C:7]=1[OH:8].[NH3:33]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]([C:29]([NH2:33])=[O:31])[C:12]3[NH:13][C:14]4[CH:15]=[C:16]([N:22]5[CH2:23][CH2:24][N:25]([CH3:28])[CH2:26][CH2:27]5)[CH:17]=[CH:18][C:19]=4[C:20]=3[N:21]=2)[CH:5]=[CH:6][C:7]=1[OH:8]
Reactant: COC(=O)c1cc(-c2ccc(O)c(Cl)c2)nc2c1[nH]c1cc(N3CCN(C)CC3)ccc12
Reactant: N
Solvent: CO
Product: CN1CCN(c2ccc3c(c2)[nH]c2c(C(N)=O)cc(-c4ccc(O)c(Cl)c4)nc23)CC1
Temperature: 80 °C
Yield: 74 %

Procedure:
A mixture of methyl 2-(3-chloro-4-hydroxyphenyl)-7-(4-methylpiperazin-1-yl)-5H-pyrido[3,2-b]indole-4-carboxylate (100 mg, 0.222 mmol) and 7N NH3 in MeOH (5 mL) in a sealed microwave vessel was heated in an oil bath at 80° C. for 16 h. After cooling to RT, the solid was collected by filtration, and washed with MeOH, and air-dried to afford 2-(3-chloro-4-hydroxyphenyl)-7-(4-methylpiperazin-1-yl)-5H-pyrido[3,2-b]indole-4-carboxamide (75 mg, 0.16 mmol, 74% yield). MS (ESI) m/z 436.10 (M+H).
Reaction SMILES: [H-].[Na+].[CH:3]1([S:6]([NH2:9])(=[O:8])=[O:7])[CH2:5][CH2:4]1.[F:10][C:11]1[CH:12]=[C:13]([C:35](O)=[O:36])[C:14]2[CH2:15][C:16]([CH3:34])([CH3:33])[CH:17]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)[CH:22]=3)[NH:18][C:19]=2[CH:20]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O>[F:10][C:11]1[CH:12]=[C:13]([C:35]([NH:9][S:6]([CH:3]2[CH2:5][CH2:4]2)(=[O:8])=[O:7])=[O:36])[C:14]2[CH2:15][C:16]([CH3:33])([CH3:34])[CH:17]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)[CH:22]=3)[NH:18][C:19]=2[CH:20]=1
Reactant: NS(=O)(=O)C1CC1
Reactant: CC1(C)Cc2c(cc(F)cc2C(=O)O)NC1c1cccc(N2CCOCC2)c1
Agent: O=C(n1ccnc1)n1ccnc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1(C)Cc2c(cc(F)cc2C(=O)NS(=O)(=O)C2CC2)NC1c1cccc(N2CCOCC2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 39.4 %

Procedure:
To a suspension of 60% sodium hydride (200 mg, 5.0 mmol) in N,N-dimethylformamide (1.5 mL) was added cyclopropanesulfonamide (630 mg, 5.2 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h. A solution of 7-fluoro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-5-carboxylic acid (200 mg, 0.52 mmol) and 1,1′-carbonyldiimidazole (170 mg, 1.04 mmol) in N,N-dimethylformamide (2.0 mL) was stirred at 70° C. After stirring at 70° C. for 1 h, the above suspension of cyclopropanesulfonamide and sodium hydride in N,N-dimethylformamide was added and the mixture was allowed to stir at 25° C. for 1 h. Purification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded cyclopropanesulfonic acid [7-fluoro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-5-carbonyl]-amide (100 mg, 40%) as a white solid: LC/MS m/e calcd for C25H30FN3O4S (M+H)+: 488.60, observed: 488.1.
Reaction SMILES: [NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][O:10][C:6]=2[C:5]([C:11](O)=[O:12])=[CH:4][C:3]=1[Cl:14].S(Cl)([Cl:17])=O>C(Cl)(Cl)Cl>[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][O:10][C:6]=2[C:5]([C:11]([Cl:17])=[O:12])=[CH:4][C:3]=1[Cl:14]
Reactant: O=S(Cl)Cl
Reactant: Nc1c(Cl)cc(C(=O)O)c2c1CCO2
Solvent: ClC(Cl)Cl
Product: Nc1c(Cl)cc(C(=O)Cl)c2c1CCO2
Yield: 100 %

Procedure:
A mixture of 4-amino-5-chloro-2,3-dihydro-7-benzofurancarboxylic acid (4.3 g) in thionyl chloride (100 ml) and CHCl3 (200 ml) was stirred and refluxed for 2 hours. The mixture was cooled and the solvent was evaporated. Toluene was added and evaporated again, yielding 4.8 g of 4-amino-5-chloro-2,3-dihydro-7-benzofurancarbonyl chloride (100% crude residue) (intermediate 7).
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[C:11]1[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][N:12]=1>CN(C)C=O>[Br:17][C:14]1[CH:15]=[CH:16][C:11]([O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[N:12][CH:13]=1
Reactant: Oc1ccccc1
Reactant: Brc1ccc(Br)nc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Brc1ccc(Oc2ccccc2)nc1
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 81 %

Procedure:
To a solution of phenol (1.97 g, 20.9 mmol) in N,N-dimethylformamide (100 mL) was added sodium hydride (1.00 g, 20.9 mmol) at 0° C., which was stirred for 5 minutes at 0° C. 2,5-Dibromopyridine (4.50 g, 19.0 mmol) was then added to this reaction solution at 0° C., and stirred for 40 minutes at room temperature. The reaction solution was then stirred for further 3 hours at 120° C. After allowing to room temperature, the reaction solution was partitioned into water and ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under a reduced pressure. The residue was purified by silica gel column chromatography (heptane:ethyl acetate=6:1) to obtain the title compound (3.85 g, 81%).
Reaction SMILES: Br[C:2]1[C:10]2[O:9][CH2:8][CH:7]([C:11]3[CH:16]=[CH:15][C:14]([CH:17]([CH3:19])[CH3:18])=[CH:13][CH:12]=3)[C:6]=2[C:5]([CH3:20])=[C:4]([NH:21][C:22](=[O:28])[CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:3]=1[CH3:29].[CH3:30][N:31]([CH3:41])[C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1>>[CH3:30][N:31]([CH3:41])[C:32]1[CH:37]=[CH:36][C:35]([C:2]2[C:10]3[O:9][CH2:8][CH:7]([C:11]4[CH:16]=[CH:15][C:14]([CH:17]([CH3:18])[CH3:19])=[CH:13][CH:12]=4)[C:6]=3[C:5]([CH3:20])=[C:4]([NH:21][C:22](=[O:28])[CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C:3]=2[CH3:29])=[CH:34][CH:33]=1
Reactant: Cc1c(Br)c2c(c(C)c1NC(=O)CC(C)(C)C)C(c1ccc(C(C)C)cc1)CO2
Reactant: CN(C)c1ccc(B(O)O)cc1
Product: Cc1c(NC(=O)CC(C)(C)C)c(C)c2c(c1-c1ccc(N(C)C)cc1)OCC2c1ccc(C(C)C)cc1
Yield: 17 %

Procedure:
Using N-(7-bromo-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide obtained in Example 35 and (4-(dimethylamino)phenyl)boronic acid, the title compound was obtained in the same manner as in Example 107. Yield: 17%. Melting point: 180-181° C. (ethyl acetate-hexane).
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:69])[NH:10][CH:11]([C:37](=[O:68])[N:38]([CH2:53][C:54]1[CH:59]=[CH:58][C:57]([O:60][CH2:61][C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)=[CH:56][CH:55]=1)[CH2:39][C:40](=[O:52])[NH:41][CH2:42][C:43]([CH3:51])([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[CH3:44])[CH2:12][C:13]1[N:14](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:15]=[N:16][CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)C>O>[CH2:1]([O:8][C:9](=[O:69])[NH:10][C@H:11]([C:37](=[O:68])[N:38]([CH2:53][C:54]1[CH:55]=[CH:56][C:57]([O:60][CH2:61][C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)=[CH:58][CH:59]=1)[CH2:39][C:40](=[O:52])[NH:41][CH2:42][C:43]([CH3:51])([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[CH3:44])[CH2:12][C:13]1[NH:14][CH:15]=[N:16][CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(CNC(=O)CN(Cc1ccc(OCc2ccccc2)cc1)C(=O)C(Cc1cncn1C(c1ccccc1)(c1ccccc1)c1ccccc1)NC(=O)OCc1ccccc1)c1ccccc1
Solvent: O
Solvent: CC(=O)O
Product: CC(C)(CNC(=O)CN(Cc1ccc(OCc2ccccc2)cc1)C(=O)[C@H](Cc1cnc[nH]1)NC(=O)OCc1ccccc1)c1ccccc1
Temperature: 90 °C
Reaction time: 0.5 h
Yield: 91.7 %

Procedure:
To a solution of the trityl compound from Step 5 (2.25 g, 2.4 mmol) was added glacial acetic acid (20 mL) and water (5 mL). The mixture was stirred at 90° C. for 30 minutes, then cooled and concentrated. The residue was taken up in ethyl acetate. The organic solution was washed twice with saturated NaHCO3, brine, and dried over MgSO4. The solution was concentrated and the compound purified by flash chromatography (0%-8% methanol in methylene chloride) to give the title compound (1.5 g, 2.2 mmol, 93%) as a white foam; ES-MS 674 (m+1).
Reaction SMILES: [CH2:1]([CH:5](C(O)=O)[N:6](C(OCC1C=CC=CC=1)=O)[CH2:7][P:8]([S:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])([S:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])=[O:9])[CH2:2][CH2:3]C.Br.C(OCC)C.[C:41]([OH:44])(=[O:43])[CH3:42]>>[CH2:5]([N:6]([CH2:7][P:8]([S:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])([S:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])=[O:9])[CH2:42][C:41]([OH:44])=[O:43])[CH2:1][CH2:2][CH3:3]
Reactant: CCCCCSP(=O)(CN(C(=O)OCc1ccccc1)C(CCCC)C(=O)O)SCCCCC
Reactant: CC(=O)O
Agent: Br
Solvent: CCOCC
Product: CCCCCSP(=O)(CN(CCCC)CC(=O)O)SCCCCC

Procedure:
n-Butyl N-carbobenzoxy-N-[bis(pentylthio)phosphinylmethyl]glycine (5.5 g., 0.01 mole) was reacted with 32% hydrogen bromide (15 ml) in glacial acetic acid at 0° C. Diethyl ether was added and the oily precipitate isolated by decantation of the ether layer. The oil was washed twice with ether, suspended in benzene and then treated with propylene oxide. The resulting solution was concentrated in vacuo to yield n-butyl N-[bis(pentylthio)phosphinylmethyl]-glycine (0.7 g., 0.002 mole) as an oil, ND27 =1.4905.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:24]=[CH:23][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][N:16]([CH2:20][CH2:21][CH3:22])[CH2:17][CH2:18][CH3:19])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[NH:25]1[CH:29]=[CH:28][N:27]=[C:26]1[CH:30]=O>CO>[CH2:17]([N:16]([CH2:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][CH2:7][C:6]2[CH:5]=[CH:4][C:3]([CH2:2][NH:1][CH2:30][C:26]3[NH:25][CH:29]=[CH:28][N:27]=3)=[CH:24][CH:23]=2)=[CH:10][CH:11]=1)[CH2:20][CH2:21][CH3:22])[CH2:18][CH3:19]
Reactant: O=Cc1ncc[nH]1
Reactant: CCCN(CCC)Cc1ccc(NCc2ccc(CN)cc2)cc1
Solvent: CO
Product: CCCN(CCC)Cc1ccc(NCc2ccc(CNCc3ncc[nH]3)cc2)cc1
Temperature: 25 °C
Reaction time: 17 h
Yield: 59.8 %

Procedure:
The compound (63.1 mg) obtained in Example 39-2 was dissolved in methanol (2.0 ml) and then added with 2-imidazole carboxaldehyde (17.9 mg), followed by stirring at room temperature for 17 hours. After the solvent had been distilled off, the residue was dried under vacuum and then dissolved in methanol (2.5 ml). Subsequently, the solution was added with sodium borohydride (14.5 mg) and stirred at room temperature for 1 hour. The reaction solution was added with a saturated aqueous ammonium chloride solution (4.0 ml) and stirred at room temperature for 30 minutes. Then, the reaction solution was added with saturated saline solution and subjected to extraction with chloroform, followed by drying with anhydrous sodium sulfate. After the solvent had been distilled off, the residue obtained was purified through silica gel column chromatography (chloroform/acetone), thereby obtaining the subject compound (45.2 mg) as a yellow solid.
Reaction SMILES: [N:1]1[N:2]=[C:3]([C:6]2[CH:11]=[CH:10][N:9]=[CH:8][CH:7]=2)[NH:4][CH:5]=1.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20]Cl)=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][N:4]2[CH:5]=[N:1][N:2]=[C:3]2[C:6]2[CH:11]=[CH:10][N:9]=[CH:8][CH:7]=2)=[CH:16][CH:15]=1
Reactant: c1cc(-c2nnc[nH]2)ccn1
Reactant: COc1ccc(CCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(Cn2cnnc2-c2ccncc2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 59.3 %

Procedure:
A mixture of 4-(4H-1,2,4-triazol-3-yl)pyridine (0.56 g, 3.8 mmol), PMBCl (0.66 g, 4.2 mmol), and K2CO3 (2.12 g, 15.3 mmol) in DMF (10 mL) was stirred for 4 h at room temperature. The reaction mixture was then diluted with water and extracted with DCM. The combined organic layers were washed with water three times, dried with Na2SO4, filtered and concentrated. The crude product was purified by column chromatography to give 4-(4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)pyridine (0.60 g).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]([C:11]2[C:19]3[O:18][CH:17]=[CH:16][C:15]=3[CH:14]=[C:13]([F:20])[CH:12]=2)=[O:10])=[CH:4][N:3]=1.[NH3:21]>C1(C)C=CC=CC=1>[NH2:21][C:6]1[C:5]([C:9]([C:11]2[C:19]3[O:18][CH:17]=[CH:16][C:15]=3[CH:14]=[C:13]([F:20])[CH:12]=2)=[O:10])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=1
Reactant: N
Reactant: O=C(c1cnc(Cl)nc1Cl)c1cc(F)cc2ccoc12
Solvent: Cc1ccccc1
Product: Nc1nc(Cl)ncc1C(=O)c1cc(F)cc2ccoc12
Yield: 52 %

Procedure:
At 20° C., a stirred suspension of (2,4-dichloro-pyrimidin-5-yl)-(5-fluoro-benzofuran-7-yl)-methanone (0.80 g, 2.6 mmol, Step E) in toluene (70 mL) was treated with a slow stream of ammonia gas (Matheson) for 1 hour. The suspension was cooled, filtered and the filter cake washed with water. The filter cake was dissolved in acetonitrile, filtered through celite and the solvent removed to give a solid. This was crystallized from acetonitrile to give 0.4 g of (4-amino-2-chloro-pyrimidin-5-yl)-(5-fluoro-benzofuran-7-yl)-methanone (52%) as a white solid. HRMS, observed: 291.0208; Calcd for (M+H)+: 291.0211
Reaction SMILES: N12CCCN=C1CCCCC2.[F:12][C:13]([F:27])([F:26])[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([C:20]2[NH:21][O:22][C:23](=[O:25])[N:24]=2)[CH:15]=1.[CH2:28]([N:31]([CH2:35][CH:36]=[CH2:37])[C:32](Cl)=[O:33])[CH:29]=[CH2:30]>N1C=CC=CC=1>[F:27][C:13]([F:12])([F:26])[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([C:20]2[N:24]([C:32]([N:31]([CH2:35][CH:36]=[CH2:37])[CH2:28][CH:29]=[CH2:30])=[O:33])[C:23](=[O:25])[O:22][N:21]=2)[CH:15]=1
Reactant: C=CCN(CC=C)C(=O)Cl
Reactant: O=c1nc(-c2cc(C(F)(F)F)ccn2)[nH]o1
Solvent: c1ccncc1
Solvent: C1CCC2=NCCCN2CC1
Product: C=CCN(CC=C)C(=O)n1c(-c2cc(C(F)(F)F)ccn2)noc1=O
Reaction time: 8 h
Yield: 73.9 %

Procedure:
To 1 ml of pyridine were added 0.28 g of 1,8-diazabicyclo[5,4,0]undec-7-ene, and 0.3 g of 3-(4-trifluoromethylpyridin-2-yl)-1,2,4-oxadiazol-5-one, and 0.29 g of N,N-diallylcarbamoyl chloride was added at room temperature. After stirring for 8 hours, the resultant solution was concentrated, and the residue was subjected to silica gel column chromatography to obtain 0.34 g of 3-(4-trifluoromethylpyridin-2-yl)-N,N-diallyl-1,2,4-oxadiazol-5-one-4-carboxamide (present compound (17)).
Reaction SMILES: [C:1]([N:4]1[C:12]2[CH:11]=[C:10]3[O:13][CH2:14][O:15][C:9]3=[CH:8][C:7]=2[CH:6]([CH2:16][CH2:17]Br)[CH2:5]1)(=[O:3])[CH3:2].[C:19]1([C:25]2[CH2:26][CH2:27][NH:28][CH2:29][CH:30]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[C:1]([N:4]1[C:12]2[CH:11]=[C:10]3[O:13][CH2:14][O:15][C:9]3=[CH:8][C:7]=2[CH:6]([CH2:16][CH2:17][N:28]2[CH2:27][CH:26]=[C:25]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:30][CH2:29]2)[CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1CC(CCBr)c2cc3c(cc21)OCO3
Reactant: C1=C(c2ccccc2)CCNC1
Product: CC(=O)N1CC(CCN2CC=C(c3ccccc3)CC2)c2cc3c(cc21)OCO3

Procedure:
In the manner described in Example 1, treatment of 5-acetyl-7-(2-bromoethyl)-6,7-dihydro-5H-1,3-dioxolo[4,5-f]-indole with 1,2,3,6-tetrahydro-4-phenylpyridine gives white crystals, m.p. 90°-91°C., after recrystallization from dilute acetone.