Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br-].[CH3:2][O:3][C:4]([C:6]1[CH:31]=[CH:30][C:9]([CH2:10][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:8][CH:7]=1)=[O:5].CC(C)([O-])C.[K+].[CH:38]([C:40]1[N:41]=[C:42]([NH:54][C:55](=[O:57])[CH3:56])[S:43][C:44]=1[CH2:45][C:46]1[CH:51]=[CH:50][C:49]([S:52][CH3:53])=[CH:48][CH:47]=1)=O>CN(C=O)C>[C:55]([NH:54][C:42]1[S:43][C:44]([CH2:45][C:46]2[CH:47]=[CH:48][C:49]([S:52][CH3:53])=[CH:50][CH:51]=2)=[C:40](/[CH:38]=[CH:10]\[C:9]2[CH:8]=[CH:7][C:6]([C:4]([O:3][CH3:2])=[O:5])=[CH:31][CH:30]=2)[N:41]=1)(=[O:57])[CH3:56]
Reactant: CSc1ccc(Cc2sc(NC(C)=O)nc2C=O)cc1
Reactant: COC(=O)c1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CC(C)(C)[O-]
Agent: [Br-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(/C=C\c2nc(NC(C)=O)sc2Cc2ccc(SC)cc2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 96.9 %

Procedure:
[4-(Methoxycarbonyl)benzyl](triphenyl)phosphonium bromide (4.81 g) and DMF (60 ml) were combined under N2 atmosphere. Then potassium tert-butoxide (1.32 g) and N-{4-formyl-5-[4-(methylthio)benzyl]-1,3-thiazol-2-yl}acetamide (3 g) were added to the suspension at 0° C. The reaction mixture was stirred at r.t. for 18 hours, poured into ice-water, and extracted with AcOEt. The organic layer was washed with water and brine, dried over anhydrous MgSO4, and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel with CHCl3/AcOEt (2:1) as an eluent. The solid was suspended in AcOEt, and the suspension was filtered. The filtrate was concentrated in vacuo to give methyl 4-((Z)-2-(2-(acetylamino)-5-[4-(methylthio)benzyl]-1,3-thiazol-4-yl}vinyl)benzoate (4.16 g) as a yellow amorphous substance.
Reaction SMILES: [C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](F)=[CH:5][CH:4]=1)#[N:2].[O:14]=[C:15]1[N:20]2[CH2:21][CH:22]3[CH2:27][CH:26]([C:19]2=[CH:18][CH:17]=[CH:16]1)[CH2:25][NH:24][CH2:23]3>>[O:14]=[C:15]1[N:20]2[CH2:21][CH:22]3[CH2:27][CH:26]([C:19]2=[CH:18][CH:17]=[CH:16]1)[CH2:25][N:24]([C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]([C:1]#[N:2])=[CH:4][CH:5]=1)[CH2:23]3
Reactant: O=c1cccc2n1CC1CNCC2C1
Reactant: N#Cc1ccc(F)c2ccccc12
Product: N#Cc1ccc(N2CC3CC(C2)c2cccc(=O)n2C3)c2ccccc12
Yield: 7.5 %

Procedure:
The title compound (3 mg, 8% yield) was prepared as described for 196MBT2-4 from 1-cyano-4-fluoronaphthalene (20 mg, 0.117 mmol) and 8-oxo-1,5,6,8-tetrahydro-2H,4H-1,5-methanopyrido[1,2-a][1,5]diazocine (89 mg, 0.468 mmol).
Reaction SMILES: [C:1]([CH2:3][CH2:4][N:5]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:6][CH2:7][C:8]#[N:9])#[N:2].[H][H]>CO>[NH2:9][CH2:8][CH2:7][CH2:6][N:5]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:4][CH2:3][CH2:1][NH2:2]
Reactant: [H][H]
Reactant: N#CCCN(CCC#N)Cc1ccccc1
Solvent: CO
Product: NCCCN(CCCN)Cc1ccccc1
Yield: 98.2 %

Procedure:
8.53 g of N,N-bis(2-cyanoethyl)benzylamine, 0.72 g of Raney Co and 100 mL of methanol were charged in an autoclave and a hydrogenation reaction was carried out at an initial hydrogen pressure of 9.0 MPa at 100° C. for 1 hour. After the catalyst was removed by filtration, the obtained filtrate was concentrated to dryness to give 8.69 g of the title compound as a pale yellow oil.
Reaction SMILES: [ClH:1].[NH2:2][C:3]1[C:4](Br)=[N:5][C:6]2[CH2:12][CH2:11][N:10]([CH2:13][CH3:14])[CH2:9][CH2:8][C:7]=2[N:15]=1.[Na].[CH3:18]O>>[ClH:1].[ClH:1].[NH2:2][C:3]1[C:4]([CH3:18])=[N:5][C:6]2[CH2:12][CH2:11][N:10]([CH2:13][CH3:14])[CH2:9][CH2:8][C:7]=2[N:15]=1
Reactant: CO
Reactant: CCN1CCc2nc(N)c(Br)nc2CC1
Agent: Cl
Agent: [Na]
Product: CCN1CCc2nc(C)c(N)nc2CC1
Temperature: 150 °C
Reaction time: 10 h

Procedure:
1 gm (3.3 mmols) of 2-amino-3-bromo-7-ethyl-6,7,8,9-tetrahydro-5H-pyrazino[2,3-d]azepine hydrochloride were admixed with a solution of 1 gm (43.5 mmols) of sodium in 50 ml of methanol, and the mixture was stirred for 10 hours at 150° C. in an autoclave. Thereafter, the reaction mixture was evaporated, the residue was taken up in 2N sodium hydroxide, and the solution was extracted with chloroform. The chloroform extract solution was evaporated, the residue was dissolved in acetone, and the solution was admixed with ethanolic hydrochloric acid, yielding the hydrochloride in the form of white crystals.
Reaction SMILES: C([O:5][C:6](=[O:27])[CH2:7][O:8][C:9]1[C:18]([NH:19][S:20]([C:23]([F:26])([F:25])[F:24])(=[O:22])=[O:21])=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=1)(C)(C)C.C1(OC)C=CC=CC=1.O.FC(F)(F)C(O)=O>C(Cl)Cl>[F:25][C:23]([F:24])([F:26])[S:20]([NH:19][C:18]1[C:9]([O:8][CH2:7][C:6]([OH:27])=[O:5])=[CH:10][C:11]2[C:16]([CH:17]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2)(=[O:21])=[O:22]
Reactant: CC(C)(C)OC(=O)COc1cc2ccccc2cc1NS(=O)(=O)C(F)(F)F
Solvent: O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(O)COc1cc2ccccc2cc1NS(=O)(=O)C(F)(F)F
Temperature: 25 °C
Reaction time: 16 h
Yield: 93 %

Procedure:
To a solution of (3-trifluoromethylsulfonylamino-2-naphthyloxy)acetic acid tert-butyl ester (1.46 g, 3.60 mmol) in CH2Cl2(37 mL)-anisole(0.1 mL)-water(0.57 mL) at room temperature under nitrogen was added trifluroacetic acid (5.7 mL). After stirring at room temperature for 16 hrs, the mixture was evaporated to dryness and chased with toluene-CH2Cl2 (1:1). The residue was triturated with Et2O to give the title compound (1.17 g, 92%) as a solid. TLC(MeOH-CH2Cl2; 1:9) Rf=0.04.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:9])=[CH:6][C:7]=1[OH:8].C(=O)([O-])[O-].[Ca+2].[C:15](Cl)(=[O:19])[CH2:16][CH2:17][CH3:18]>O1CCOCC1>[OH:8][C:7]1[CH:6]=[C:5]([CH3:9])[CH:4]=[CH:3][C:2]=1[NH:1][C:15](=[O:19])[CH2:16][CH2:17][CH3:18]
Reactant: CCCC(=O)Cl
Reactant: Cc1ccc(N)c(O)c1
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: C1COCCO1
Product: CCCC(=O)Nc1ccc(C)cc1O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 33.4 %

Procedure:
To 30 ml of dioxane, there were added 1.50 g (12.6 mmol) of 6-amino-m-cresol and 0.6 g (6.0 mmol) of calcium carbonate. To the solution thus obtained, there was added 1.02 g of butanoyl chloride over 10 minutes, followed by stirring at room temperature for 30 minutes. After the completion of the reaction, the inorganic salt was filtered and 150 ml of water was poured thereto. Then the mixture was extracted with 150 ml of ethyl acetate, washed with a saturated aqueous solution of common salt and dried over anhydrous Glauber's salt. After distilling off the solvent under reduced pressure, a red oily product was obtained. This product was crystallized by adding thereto 15 ml of hexane and 6 ml of ethyl acetate, and then filtered and dried. Thus 0.62 g (3.2 mmol) of N-(2-hydroxy-4-methylphenyl)butanamide was obtained as colorless crystals. The yield was 25%.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][C:3]=1[C:11]1[NH:15][C:14]([C:16]2([CH3:20])[CH2:19][O:18][CH2:17]2)=[N:13][C:12]=1[CH3:21].CC1NC(C2C=C(C=CC=2C)C(O)=O)=C(C)N=1.Cl.[F:40][C:41]1([C:45]2[CH:52]=[CH:51][C:48]([C:49]#[N:50])=[CH:47][CH:46]=2)[CH2:44][NH:43][CH2:42]1.Cl.N1CC(C2C=CC(C#N)=CC=2)C1>>[F:40][C:41]1([C:45]2[CH:46]=[CH:47][C:48]([C:49]#[N:50])=[CH:51][CH:52]=2)[CH2:42][N:43]([C:6](=[O:7])[C:5]2[CH:9]=[CH:10][C:2]([CH3:1])=[C:3]([C:11]3[NH:15][C:14]([C:16]4([CH3:20])[CH2:17][O:18][CH2:19]4)=[N:13][C:12]=3[CH3:21])[CH:4]=2)[CH2:44]1
Reactant: N#Cc1ccc(C2(F)CNC2)cc1
Reactant: Cc1ccc(C(=O)O)cc1-c1[nH]c(C2(C)COC2)nc1C
Agent: Cc1nc(C)c(-c2cc(C(=O)O)ccc2C)[nH]1
Agent: Cl
Agent: N#Cc1ccc(C2CNC2)cc1
Product: Cc1ccc(C(=O)N2CC(F)(c3ccc(C#N)cc3)C2)cc1-c1[nH]c(C2(C)COC2)nc1C

Procedure:
The title compound was prepared using standard chemical manipulations and procedures similar to those used for the preparation of compound 5, except 4-methyl-3-(4-methyl-2-(3-methyloxetan-3-yl)-1H-imidazol-5-yl)benzoic acid (compound 177.2) was used in place of 3-(2,4-dimethyl-1H-imidazol-5-yl)-4-methylbenzoic acid (compound 5.7) and 4-(3-fluoroazetidin-3-yl)benzonitrile hydrochloride (compound 43.4) was used in place of 4-(azetidin-3-yl)benzonitrile hydrochloride (compound 5.2). m/z (ES+) 445 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ 11.80 (br, 1H), 7.96 (dd, J=8.0 Hz, 2.4 Hz, 2H), 7.80 (d, J=8.4 Hz, 2H), 7.67-7.52 (m, 2H), 7.44-7.33 (m, 1H), 4.95-4.89 (m, 2H), 4.89-4.46 (m, 4H), 4.46-4.40 (m, 2H), 3.36 and 2.26 (2 singlets, CH3, 3H), 2.17 and 2.03 (2 singlets, CH3, 3H), 1.69 and 1.68 (2 singlets, CH3, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([N:13]2[CH2:19][CH2:18][C:17](=[O:20])[N:16]([CH2:21][CH2:22][CH2:23][O:24]C3CCCCO3)[CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>CO>[Cl:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([N:13]2[CH2:19][CH2:18][C:17](=[O:20])[N:16]([CH2:21][CH2:22][CH2:23][OH:24])[CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: O=C(/C=C/c1ccc(Cl)c(Cl)c1)N1CCC(=O)N(CCCOC2CCCCO2)CC1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: CO
Product: O=C(/C=C/c1ccc(Cl)c(Cl)c1)N1CCC(=O)N(CCCO)CC1
Temperature: 55 °C
Reaction time: 0.5 h

Procedure:
A solution of 1.30 g (2.85 mmol) of 1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-4-[3-(tetrahydro-pyran-2-yloxy)-propyl]-[1,4]diazepan-5-one in 6 ml of methanol was treated with 0.22 g (0.86 mmol) of pyridinium toluene-4-sulfonate and stirred at 55° C. for 30 min. The reaction was cooled and extracted with aqueous 10% KHSO4/Et2O (3×). The organic phases were washed with aqueous saturated NaHCO3, aqueous 10% NaCl, dried (Na2SO4) and evaporated to give after crystallization (Et2O) 0.98 g (92%) of the title compound as white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([OH:14])=O)[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17].FC1C(OC(N(C)C)=[N+](C)C)=C(F)C(F)=C(F)C=1F.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[CH3:63][N:64]([CH3:72])[C:65]([C@@H:67]1[CH2:71][CH2:70][CH2:69][NH:68]1)=[O:66]>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12]([N:68]1[CH2:69][CH2:70][CH2:71][C@H:67]1[C:65]([N:64]([CH3:72])[CH3:63])=[O:66])=[O:14])[N:8]=[CH:7][N:6]=[C:5]2[NH:15][CH:16]([C:18]1[NH:22][C:21]2[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:20]=2[N:19]=1)[CH3:17]
Reactant: CC(Nc1ncnc2cc(C(=O)O)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1
Reactant: CN(C)C(=O)[C@@H]1CCCN1
Agent: CN(C)C(Oc1c(F)c(F)c(F)c(F)c1F)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(Nc1ncnc2cc(C(=O)N3CCC[C@H]3C(=O)N(C)C)c(Cl)cc12)c1nc2cc(Cl)ccc2[nH]1

Procedure:
Prepared analogously to Example 37a from 6-chloro-4-[1-(5-chloro-1H-benzimidazol-2-yl)-ethylamino]-7-hydroxycarbonyl-quinazoline, pentafluorophenyl-tetramethyluronium-hexafluorophosphate (PFTU), diisopropylethylamine and (S)-2-dimethylaminocarbonyl-pyrrolidine in DMSO at ambient temperature.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[N:13]([CH3:14])[C:12](=[O:15])[CH2:11][N:10]([N+]([O-])=O)[C:9]([O:25][CH3:26])([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:8]=2[CH:27]=1.O.C(OCC)C>CN(C)C=O>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[N:13]([CH3:14])[C:12](=[O:15])[CH:11]=[N:10][C:9]([O:25][CH3:26])([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:8]=2[CH:27]=1
Reactant: COC1(c2ccccc2)c2cc(Cl)ccc2N(C)C(=O)CN1[N+](=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOCC
Product: COC1(c2ccccc2)N=CC(=O)N(C)c2ccc(Cl)cc21
Temperature: -30 °C
Yield: 44.1 %

Procedure:
To a solution of sodium hydride (50% suspension in a mineral oil; 200 mg) in dry dimethylformamide (7.5 ml), 7-chloro-5-methoxy-1-methyl-4-nitro-5phenyl-1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-one (500 mg) is added under cooling at -30° C. and with stirring, and the resultant mixture is stirred at -10° C. for 30 minutes. The reaction mixture is poured into icy water and shaken with diethyl ether. The organic layer is washed with water, dried over sodium sulfate, and evaporated to remove the solvent. The residue is crystallized from diethyl ether to give 7-chloro-5-methoxy-1-methyl-5-phenyl-1,5-dihydro-2H-1,4-benzodiazepin-2-one (192 mg) as colorless prisms melting at 146.5 to 147° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]1[C:15]([O:18][CH3:19])=[N:16][N:17]=[C:10]1[C:9](Cl)=[N:8]2)=[O:4].[N:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][NH2:29])=[CH:23][CH:22]=1.C(=O)(O)[O-].[Na+]>CN(C=O)C.O.CCOC(C)=O>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]1[C:15]([O:18][CH3:19])=[N:16][N:17]=[C:10]1[C:9]([NH:29][CH2:28][CH2:27][C:24]1[CH:25]=[CH:26][N:21]=[CH:22][CH:23]=1)=[N:8]2)=[O:4]
Reactant: COC(=O)c1ccc2c(c1)nc(Cl)c1nnc(OC)n12
Reactant: NCCc1ccncc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COC(=O)c1ccc2c(c1)nc(NCCc1ccncc1)c1nnc(OC)n12
Temperature: 50 °C
Reaction time: 15 h

Procedure:
A mixture of 4-chloro-1-methoxy-[1,2,4]triazolo[4,3-a]quinoxaline-7-carboxylic acid methyl ester (80 mg), 2-(4-pyridyl)ethylamine (50 mg), and sodium bicarbonate (45 mg) in DMF (2 mL) was stirred at 50° C. for 15 hrs. The mixture was cooled to 23° C., and then diluted with water and EtOAc. A precipitate formed which was isolated by filtration to afford 1-methoxy-4-(2-pyridin-4-ylethylamino)-[1,2,4]triazolo[4,3-a]quinoxaline-7-carboxylic acid methyl ester. MS (M+H)+=379.3.
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[O:10][CH3:11].[CH3:12][N:13]([CH3:18])[CH2:14][CH2:15][CH2:16][OH:17].C[Si](C)(C)[N-][Si](C)(C)C.[K+]>O1CCCC1>[CH3:12][N:13]([CH3:18])[CH2:14][CH2:15][CH2:16][O:17][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[O:10][CH3:11]
Reactant: COc1cc(C#N)ccc1F
Reactant: CN(C)CCCO
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Product: COc1cc(C#N)ccc1OCCCN(C)C
Temperature: 65 °C
Reaction time: 6 h

Procedure:
15 g 4-Fluoro-3-methoxybenzonitrile and 12 mL 3-dimethylamino-1-propanol was dissolved 150 mL tetrahydrofuran. 21.7 g Potassium hexamethyldisilazide was added and the mixture was stirred at 65° C. for 6 h. the mixture was concentrated to 50 mL and the residue diluted in ethyl acetate, washed with water and saturated sodium chloride solution and the organic phase dried over magnesium sulfate.
Reaction SMILES: [CH2:1]([C:3]1[N:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[C:21]#[N:22])=[CH:11][CH:10]=2)[C:6]2[CH:23]=[C:24]([C:27]3[N:31]([CH3:32])[C:30]4[CH:33]=[CH:34][CH:35]=[CH:36][C:29]=4[N:28]=3)[CH:25]=[CH:26][C:5]=2[N:4]=1)[CH3:2].[N-:37]=[N+:38]=[N-:39].[Na+]>CN(C)C=O>[CH2:1]([C:3]1[N:7]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[C:21]3[NH:39][N:38]=[N:37][N:22]=3)=[CH:13][CH:14]=2)[C:6]2[CH:23]=[C:24]([C:27]3[N:31]([CH3:32])[C:30]4[CH:33]=[CH:34][CH:35]=[CH:36][C:29]=4[N:28]=3)[CH:25]=[CH:26][C:5]=2[N:4]=1)[CH3:2]
Reactant: [N-]=[N+]=[N-]
Reactant: CCc1nc2ccc(-c3nc4ccccc4n3C)cc2n1Cc1ccc(-c2ccccc2C#N)cc1
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCc1nc2ccc(-c3nc4ccccc4n3C)cc2n1Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1

Procedure:
Prepared analogously to Example 41 from 4'-[[2-ethyl-6-(1-methyl-benzimidazol-2-yl)-benzimidazol-1-yl]methyl]-2-cyano-biphenyl and sodium azide in dimethylformamide.
Reaction SMILES: [CH2:1]([S:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11](Br)[C:10]=1[CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:17]1[CH2:21][CH2:20][CH2:19][C:18]1=[O:22]>>[CH2:1]([S:8][C:9]1[C:10]([CH3:16])=[C:11]([N:17]2[CH2:21][CH2:20][CH2:19][C:18]2=[O:22])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CCCN1
Reactant: Cc1c(Br)cccc1SCc1ccccc1
Product: Cc1c(SCc2ccccc2)cccc1N1CCCC1=O

Procedure:
Intermediate 24 (14.08 g, 48 mmol) and pyrrolidin-2-one (4.9 g, 57.6 mmol) were converted to intermediate 25 as described in example 1; 1.5). The crude product (14.6 g) was used without purification in the next step.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[CH:5][C:4]=1[N+:15]([O-])=O.CO>ClCCl.[Pd]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:10][CH2:11][O:12][CH2:13][CH2:14]2)=[CH:5][C:4]=1[NH2:15]
Reactant: COc1ccc(N2CCOCC2)cc1[N+](=O)[O-]
Agent: [Pd]
Solvent: ClCCl
Solvent: CO
Product: COc1ccc(N2CCOCC2)cc1N
Yield: 87.7 %

Procedure:
4-(4-Methoxy-3-nitro-phenyl)-morpholine (6 g) is hydrogenated in dichloromethane (100 ml) and methanol (600 ml) using palladium on carbon (10%, 600 mg) for 12 hours. The catalyst is removed by filtration and the solution evaporated in vacuo. Purification by flash chromatography (silica, eluent ethyl acetate/n-hexane 1:1, then) affords the product as off-white solid (4.6 g, 88%). MS: m/e=209 (M+H+).
Reaction SMILES: C([O:3][C:4](=[O:29])[CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][C:16]2[N:17]=[C:18]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[O:19][C:20]=2[CH3:21])=[CH:9][C:8]=1[OH:28])C.[Li+].[OH-]>O1CCCC1>[CH3:21][C:20]1[O:19][C:18]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[N:17][C:16]=1[CH2:15][CH2:14][O:13][C:10]1[CH:11]=[CH:12][C:7]([CH2:6][CH2:5][C:4]([OH:29])=[O:3])=[C:8]([OH:28])[CH:9]=1
Reactant: CCOC(=O)CCc1ccc(OCCc2nc(-c3ccccc3)oc2C)cc1O
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Cc1oc(-c2ccccc2)nc1CCOc1ccc(CCC(=O)O)c(O)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 49.2 %

Procedure:
3-{2-Hydroxy-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-propionic acid ethyl ester (60 mg, 0.15 mmol) was dissolved in tetrahydrofuran (5 mL) and treated with LiOH (1 mL, 1M). After stirring 18 hours at ambient temperature, the reaction was evaporated and partitioned between NH4Cl (sat.) and ethyl acetate. Extraction with ethyl acetate, followed by drying over anhydrous Na2SO4, and evaporation of solvent provided 27.1 mg of the title compound. MS m/z 368 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([S:10](Cl)(=[O:12])=[O:11])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[CH2:14]1[C:19]2[NH:20][C:21]3[C:26]([C:18]=2[CH2:17][CH:16]([C:27]([NH2:29])=[O:28])[NH:15]1)=[CH:25][CH:24]=[CH:23][CH:22]=3.C(N(CC)CC)C.O>CC(C)=O.CN(C=O)C>[N+:1]([C:4]1[CH:5]=[C:6]([S:10]([N:15]2[CH:16]([C:27]([NH2:29])=[O:28])[CH2:17][C:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[NH:20][C:19]=3[CH2:14]2)(=[O:12])=[O:11])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)Cl)c1
Reactant: NC(=O)C1Cc2c([nH]c3ccccc23)CN1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CC(C)=O
Product: NC(=O)C1Cc2c([nH]c3ccccc23)CN1S(=O)(=O)c1cccc([N+](=O)[O-])c1
Reaction time: 8 h

Procedure:
3-nitro benzene sulphonyl chloride (0.53 gm, 2.4 mmol) in dry acetone was added to a stirred solution of dl 1,2,3,4-tetrahydro-9H-pyrido(3,4-b)indole-3-amide (0.430 gm, 2.0 mmol) and dry triethylamine (0.56 ml, 4.0 mmol) in dry DMF (8 ml) during 15 min and was allowed to sir for 8 hrs. at room temperature. The reaction mixture was allowed to stirr for 8hrs. at room temperature. Water (20 ml) was added to the reaction mixture and extracted with chloroform (3×15 ml). The extract was dried over Na2SO4 and concentrated over reduced pressure to give 2-[3-nitrobenzenesulfonyl]-1,2,3,4,-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic acid amide which was purified by column chromatography over silica gel using 2% methanol chloroform as eluent. Yield=0.400 gm (50%). m.p.=252° C. Mass (FAB) m/z=401 (M+). IR (KBr cm−1): 3459, 3378, 1692, 1618, 1528, 1353, 11173, 760. H1NMR (200MHz, CDCl3+DMSO d6): δ2.88 (m, 1H), δ3.33 (d, 1H), δ4.73 (d, 1H), δ4.93 (d, 1H), δ5.06 (d, 1H), δ6.41 (s, 1H), δ6.89-7.31 (m, 3H), δ7.63-7.71 (m, 3H), δ8.13-8.17 (d, 1H), δ8.30 (d, 1H), δ8.59 (d, 1H), δ 10.27 (s, 1H). Molecular Formula=C18H16N4O5S.
Reaction SMILES: C([O:3][C:4](=[O:36])[CH2:5][C:6]1[S:10][C:9]([C:11]([C:14]2[C:19]([Cl:20])=[CH:18][C:17]([N:21]3[C:26](=[O:27])[NH:25][C:24](=[O:28])[CH:23]=[N:22]3)=[CH:16][C:15]=2[Cl:29])([CH3:13])[CH3:12])=[N:8][C:7]=1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)C.[OH-].[Na+].Cl.CCOC(C)=O>CO.C1COCC1>[Cl:20][C:19]1[CH:18]=[C:17]([N:21]2[C:26](=[O:27])[NH:25][C:24](=[O:28])[CH:23]=[N:22]2)[CH:16]=[C:15]([Cl:29])[C:14]=1[C:11]([C:9]1[S:10][C:6]([CH2:5][C:4]([OH:36])=[O:3])=[C:7]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:8]=1)([CH3:13])[CH3:12]
Reactant: CCOC(=O)Cc1sc(C(C)(C)c2c(Cl)cc(-n3ncc(=O)[nH]c3=O)cc2Cl)nc1-c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(c1nc(-c2ccccc2)c(CC(=O)O)s1)c1c(Cl)cc(-n2ncc(=O)[nH]c2=O)cc1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.5 %

Procedure:
A mixture of intermediate (9) (0.00183 mole) and NaOH 1N (0.0055 mole) in CH3OH (25 ml) and THF (25 ml) was stirred overnight at RT. The reaction mixture was acidified with 1N HCl (8 ml) and the resulting product was taken up into EtOAc. The organic layer was washed with brine, dried, filtered and the solvent was evaporated. The residue was crystallized from CH3CN. The precipitate was filtered off, washed with DIPE, and dried, yielding 0.8 g (79%) of 2-[1-[2,6-dichloro-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)yl)phenyl]-1-methylethyl]-4-phenyl-5-thiazoleacetic acid (intermediate 10).
Reaction SMILES: O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[Br:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(O)(=O)C.ClC(Cl)C>[Br:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][CH:2]2[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]2)=[CH:18][CH:17]=1
Reactant: Nc1ccc(Br)cc1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(Cl)Cl
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N1CCC(Nc2ccc(Br)cc2)CC1

Procedure:
Using similar reaction conditions as described in step-iii of example-133, tert-butyl 4-oxopiperidine-1-carboxylate (3 gm, 15.0 mmol) and 4-bromoaniline (2.59 gm, 15.0 mmol) were reacted using Na(OAc)3BH (105 mg, 0.494 mmol) and 3 drops of acetic acid in dichloroethane (80 mL) to afford 6.7 gm (crude) of the titled compound. MS: m/z=256.8 (M-Boc+1).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[NH:20][C:19](=[O:24])[CH2:18][CH2:17]3)=[CH:4][C:3]=1[CH3:25].[OH:26]O>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[NH:20][C:19](=[O:24])[CH2:18][CH2:17]3)=[O:26])=[CH:4][C:3]=1[CH3:25]
Reactant: OO
Reactant: Cc1cc(SCCCCOc2ccc3c(c2)CCC(=O)N3)ccc1Br
Product: Cc1cc(S(=O)CCCCOc2ccc3c(c2)CCC(=O)N3)ccc1Br

Procedure:
Prepared analogous to Example 123 from 6-[4-(4-bromo-3-methyl-phenylmercapto)-butoxy]-3,4-dihydro-carbostyril and hydrogen peroxide.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[CH2:3][O:4][CH2:5][CH2:6][O:7][C:8]1[N:13]=[CH:12][C:11]([C:14](=O)[CH3:15])=[CH:10][CH:9]=1.[CH3:19][C:20]([S@:23]([NH2:25])=[O:24])([CH3:22])[CH3:21]>>[CH3:19][C:20]([S@:23]([NH:25][CH:14]([C:11]1[CH:12]=[N:13][C:8]([O:7][CH2:6][CH2:5][O:4][CH2:3][C:2]([F:18])([F:17])[F:1])=[CH:9][CH:10]=1)[CH3:15])=[O:24])([CH3:22])[CH3:21]
Reactant: CC(=O)c1ccc(OCCOCC(F)(F)F)nc1
Reactant: CC(C)(C)[S@](N)=O
Product: CC(N[S@](=O)C(C)(C)C)c1ccc(OCCOCC(F)(F)F)nc1
Yield: 24 %

Procedure:
The title compound is prepared in 24% yield (0.33 g, yellow oil) from 1-(6-(2-(2,2,2-trifluoroethoxy)ethoxy)pyridin-3-yl)ethanone (1.0 g, 3.80 mmol, Step-1) and (R)-2-methylpropane-2-sulfinamide by the similar manner in Step-4 of Amine-1.