Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]([C:5]1[C:13]2[N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[CH:16][CH:15]=3)[NH:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4].[OH-].[Na+].Cl>C1COCC1.O>[C:17]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:18]=[CH:19][C:14]([C:11]2[NH:10][C:9]3[CH:8]=[CH:7][CH:6]=[C:5]([C:3]([OH:4])=[O:2])[C:13]=3[N:12]=2)=[CH:15][CH:16]=1
Reactant: COC(=O)c1cccc2[nH]c(-c3ccc(-c4ccccc4)cc3)nc12
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1cccc2[nH]c(-c3ccc(-c4ccccc4)cc3)nc12
Temperature: 25 °C

Procedure:
2-Biphenyl-4-yl-1H-benzoimidazole-4-carboxylic acid methyl ester (180 mg, 0.54 mmol) was taken in THF (20 mL) and was refluxed with 5N NaOH (5 mL) solution for 14 h. It was then cooled to room temperature; THF was removed under reduced pressure to obtain a thick mass. This residue was diluted with water (10 mL) and adjusted pH to 2 with conc. hydrochloric acid. The precipitated solid was filtered, washed with water and dried in a vacuum oven to obtain compound the required compound as a pale yellow solid.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7](/[CH:12]=[CH:13]/[C:14]([O:16][CH3:17])=[O:15])[CH:6]=[CH:5]2.C(N(CC)CC)C.[C:25](Cl)(=[O:29])[C:26]([CH3:28])=[CH2:27]>C1COCC1>[CH3:28][C:26](=[CH2:27])[C:25]([O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7](/[CH:12]=[CH:13]/[C:14]([O:16][CH3:17])=[O:15])[CH:6]=[CH:5]2)=[O:29]
Reactant: COC(=O)/C=C/c1ccc2cc(O)ccc2c1
Reactant: C=C(C)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C=C(C)C(=O)Oc1ccc2cc(/C=C/C(=O)OC)ccc2c1
Temperature: 0 °C

Procedure:
0.89 g (3.9 mmol) of methyl (E)-3-(6-hydroxy-naphthalen-2-yl)-acrylate, a spatula tip of BHT and 0.66 ml of triethylamine were dissolved in 10 ml of THF. After cooling to 0° C. a solution of 0.39 ml (4.07 mmol) of methacryloyl chloride in 4 ml of THF was added dropwise within 30 minutes. The white suspension was stirred at 0° C. for a further hour and then partitioned in ether and water. The organic phase was back-washed twice with water and the aqueous phases were back-washed twice with diethyl ether. The combined organic phases were dried over magnesium sulphate, filtered over Celite and evaporated completely in a vacuum. The crude product was recrystallized from a mixture of 5 ml of hexane and 20 ml of toluene. This gave 0.92 g of white (E)-2-(2-methoxycarbonyl-vinyl)-naphthalen-6-yl 2-methyl-acrylate.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=1)[C:9]1[C:10]([Cl:29])=[C:11]([C:17]2(O)[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:18]2)[CH:12]=[C:13]([C:15]#[N:16])[CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(S(F)(F)[F:45])CC)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=1)[C:9]1[C:10]([Cl:29])=[C:11]([C:17]2([F:45])[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:18]2)[CH:12]=[C:13]([C:15]#[N:16])[CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1ccc(CN(C(=O)OC(C)(C)C)c2cc(C#N)cc(C3(O)CN(C(=O)OC(C)(C)C)C3)c2Cl)cc1
Reactant: CCN(CC)S(F)(F)F
Solvent: ClCCl
Product: COc1ccc(CN(C(=O)OC(C)(C)C)c2cc(C#N)cc(C3(F)CN(C(=O)OC(C)(C)C)C3)c2Cl)cc1
Temperature: 0 °C
Yield: 78.4 %

Procedure:
To a solution of tert-butyl 3-(3-((tert-butoxycarbonyl)(4-methoxybenzyl)amino)-2-chloro-5-cyanophenyl)-3-hydroxyazetidine-1-carboxylate (408 mg, 0.75 mmol) in dry CH2Cl2 (12 mL) at −78° C. under nitrogen was added diethylaminosulfur trifluoride (153 μL, 0.90 mmol). The mixture was allowed to warm to 0° C. over 4 h and quenched by adding 1M aqueous NaOH at −5° C. The reaction mixture was diluted with EtOAc, washed with water, brine, and dried over sodium sulfate. Solvent was removed. The residue was purified by ISCO column (12 g) chromatography, eluting with hexane containing 0 to 40% EtOAc to afford tert-butyl 3-(3-((tert-butoxycarbonyl)(4-methoxybenzyl)amino)-2-chloro-5-cyanophenyl)-3-fluoroazetidine-1-carboxylate (321 mg).
Reaction SMILES: [O:1]=[C:2]1[NH:7][C:6](=[O:8])[CH:5]=[CH:4][NH:3]1.Br[CH2:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[O:1]=[C:2]1[NH:7][C:6](=[O:8])[CH:5]=[CH:4][N:3]1[CH2:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12]
Reactant: O=C(CBr)OCc1ccccc1
Reactant: O=c1cc[nH]c(=O)[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=C(Cn1ccc(=O)[nH]c1=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 60.3 %

Procedure:
To a solution of 2,4-dioxopyrimidine (1.0 g) in anhydrous DMF (10 ml) were added benzyl bromoacetate (2.5 g) and potassium carbonate (2.5 g). After stirring at room temperature for 15 hours, the reaction mixture was poured into water and extracted with ethyl acetate. The organic phase was washed with brine and then dried with magnesium sulfate, filtered and evaporated under reduced pressure. The precipitate was washed with diethyl ether to give phenylmethyl 2-(2,4-dioxo-1,3-dihydropyrimidinyl)acetate (1.4 g) as a colorless solid.
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[C:14]2[C:5]([S:6][C:7]3[CH:8]=[C:9]([C:16]4[NH:20][N:19]=[N:18][N:17]=4)[CH:10]=[CH:11][C:12]=3[CH2:13]2)=[CH:4][CH:3]=1.ClC1C=C(C=CC=1)C(OO)=[O:26]>CC(C)=O.O>[Cl:1][C:2]1[CH:15]=[C:14]2[C:5]([S:6](=[O:26])[C:7]3[CH:8]=[C:9]([C:16]4[NH:20][N:19]=[N:18][N:17]=4)[CH:10]=[CH:11][C:12]=3[CH2:13]2)=[CH:4][CH:3]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Clc1ccc2c(c1)Cc1ccc(-c3nnn[nH]3)cc1S2
Solvent: O
Solvent: CC(C)=O
Product: O=S1c2ccc(Cl)cc2Cc2ccc(-c3nnn[nH]3)cc21
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
7-Chloro-3(5-tetrazolyl)thioxanthene (100g.) was suspended in a mixture of acetone (40 ml.) and water (10 ml.) and 85% m-chloroperoxybenzoic acid (0.61g.) was added in portions. After 1.5 hr. stirring at 25° C. the mixture was diluted with water and allowed to stand overnight. The solid product was filtered off and dried, then boiled under refulx with ether (50 ml.), filtered, washed with ether, and dried, yielding 7-chloro-3(5-tetrazolyl)thioxanthene-10-oxide which had no defined melting point.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([CH:11]=O)=[C:7]2[C:3]=1[CH:4]([OH:23])[N:5]([C:14]([CH3:22])([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15])[C:6]2=[O:13].[C:24]1([NH2:31])[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[NH2:30].CCCCCC>[N+](C1C=CC=CC=1)([O-])=O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[NH:31][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[N:30]=2)=[C:7]2[C:3]=1[CH:4]([OH:23])[N:5]([C:14]([CH3:22])([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15])[C:6]2=[O:13]
Reactant: Nc1ccccc1N
Reactant: CC(C)(c1ccccc1)N1C(=O)c2c(C=O)ccc(Cl)c2C1O
Solvent: CCCCCC
Solvent: O=[N+]([O-])c1ccccc1
Product: CC(C)(c1ccccc1)N1C(=O)c2c(-c3nc4ccccc4[nH]3)ccc(Cl)c2C1O
Temperature: 130 °C
Reaction time: 5.2 h
Yield: 33.8 %

Procedure:
4-Chloro-3-hydroxy-7-formyl-2-(1-methyl-1-phenylethyl)isoindolinone (100 mg, 0.303 mmol) was dissolved in nitrobenzene (2 mL), and the solution was added with o-phenylenediamine (49 mg, 0.45 mmol), followed by stirring at 130° C. for 5.2 hours. The reaction mixture was added with hexane and the obtained solid was collected by filtration and purified by preparative thin-layer chromatography (hexane/ethyl acetate=2/1, 1/1) to obtain 4-chloro-3-hydroxy-7-(1H-benzoimidazol-2-yl)-2-(1-methyl-1-phenylethyl)isoindolinone (42.8 mg, yield 34%).
Reaction SMILES: CC([CH2:5][N:6]([CH2:10][CH2:11][NH:12][C:13]1[N:14]=[C:15]([C:32]2[CH:37]=[C:36]([C:38]([NH:40][CH:41]([CH3:43])[CH3:42])=[O:39])[CH:35]=[CH:34][C:33]=2[CH3:44])[C:16]2[CH2:21][NH:20][C:19](=[O:22])[N:18]([C:23]3[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=3[F:30])[C:17]=2[N:31]=1)C(=O)[O-])(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:30][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([F:29])[C:23]=1[N:18]1[C:17]2[N:31]=[C:13]([NH:12][CH2:11][CH2:10][NH:6][CH3:5])[N:14]=[C:15]([C:32]3[CH:37]=[C:36]([CH:35]=[CH:34][C:33]=3[CH3:44])[C:38]([NH:40][CH:41]([CH3:42])[CH3:43])=[O:39])[C:16]=2[CH2:21][NH:20][C:19]1=[O:22]
Reactant: Cc1ccc(C(=O)NC(C)C)cc1-c1nc(NCCN(CC(C)(C)C)C(=O)[O-])nc2c1CNC(=O)N2c1c(F)cccc1F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CNCCNc1nc(-c2cc(C(=O)NC(C)C)ccc2C)c2c(n1)N(c1c(F)cccc1F)C(=O)NC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 72 %

Procedure:
To a solution of 1,1-dimethylethyl(2-{[8-(2,6-difluorophenyl)-4-(2-methyl-5-{[(1-methylethyl)amino]carbonyl}phenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-2-yl]amino}ethyl)methylcarbamate (18 mg, 0.030 mmol) in DCM (5 mL) was added TFA (0.05 mL). The reaction mixture was stirred at room temperature overnight, quenched with triethylamine (0.2 mL) at −78° C. The residue was mixed with H2O (5.0 mL). The organic layer was separated and the aqueous layer was extracted with DCM (3×15 mL). The combined organic phases were washed with saturated aq. NaCl, dried over Na2SO4, filtered, and concentrated. Purification via a CombiFlash system (90% CH2Cl2/7% MeOH/3% NH4OH) then afforded the title compound (11 mg, 73%). LC-MS (ES) m/z 510 (M+H)+; 1H-NMR(MeOD) δ 1.27 (d, 6H), 2.26 (s, 3H), 2.30 (s, 3H), 2.56 (m, 2H), 3.22 (m, 2H), 4.11 (s, 2H), 4.23 (m, 1H), 7.15 (t, 2H), 7.46 (d, 1H), 7.52 (m, 1H), 7.69 (s, 1H), 7.85 (d, 1H).
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[N:7]1([CH:16]2[CH2:21][CH2:20][O:19][C:17]2=[O:18])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8]1>C1COCC1>[N:7]1([CH:16]([CH2:21][CH2:20][OH:19])[CH2:17][OH:18])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8]1
Reactant: O=C1OCCC1n1ccc2ccccc21
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCCC(CO)n1ccc2ccccc21
Temperature: 0 °C

Procedure:
To an ice cooled suspension of LAH (0.84 g, 0.022 mol) in dry THF (60 mL) was added 2-(indol-1-yl)butyrolactone (4 g, 0.02 mol). After 1 hour the mixture was quenched successively with water (0.84 mL), 15% aqueous sodium hydroxide (0.84 mL), and water (2.5 mL). The reaction was filtered and the filtrate was dried, and evaporated. The material obtained, 2.5 g of colorless oil (61% of theory), was used directly in the next reaction.
Reaction SMILES: [CH2:1]([N:4]1[CH2:9][CH2:8][CH2:7][CH2:6][C:5]1=[O:10])[CH2:2][CH3:3].C([N-]C(C)C)(C)C.[Li+].[Br:19][C:20]1[C:21](=O)[CH2:22][CH2:23][CH2:24][C:25]=1[O:26]C>C1C=CC=CC=1.C1COCC1>[Br:19][C:20]1[C:25](=[O:26])[CH2:24][CH2:23][CH2:22][C:21]=1[CH:6]1[CH2:7][CH2:8][CH2:9][N:4]([CH2:1][CH2:2][CH3:3])[C:5]1=[O:10]
Reactant: CCCN1CCCCC1=O
Reactant: COC1=C(Br)C(=O)CCC1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: c1ccccc1
Product: CCCN1CCCC(C2=C(Br)C(=O)CCC2)C1=O

Procedure:
A solution of 1-propyl-2-piperidone (50 mM) in benzene (40 ml) was added dropwise to a solution of lithium di-isopropylamide [ex n-butyl lithium in hexane (32.3 ml, 50 mM), di-isopropylamine (7 ml, 50 mM) and THF (33 ml)]. A solution of 2-bromo-3-methoxycyclohex-2-en-1-one (10.25 g, 50 mM) in THF (40 ml) was added, and after 5 minutes the mixture was quenched by pouring on to excess aqueous hydrochloric acid. Ether extraction followed by passage through a short silica pad using ethyl acetate as eluant gave the title compound as a colourless oil (10.75 g).
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[CH:9]=[CH:8][CH:7]=[CH:6][C:4]=1[NH2:5].[CH3:12][CH:13]([C:19](=O)[CH3:20])[C:14](OCC)=[O:15]>>[CH3:20][C:19]1[C:13]([CH3:12])=[C:14]([OH:15])[C:6]2[C:4](=[C:3]([C:2]([F:10])([F:11])[F:1])[CH:9]=[CH:8][CH:7]=2)[N:5]=1
Reactant: Nc1ccccc1C(F)(F)F
Reactant: CCOC(=O)C(C)C(C)=O
Product: Cc1nc2c(C(F)(F)F)cccc2c(O)c1C

Procedure:
Prepared according to procedure R using 2-(trifluoromethyl)aniline (1.61 g, 10 mmol) and ethyl 2-methyl-3-oxobutanoate (2.89 g, 20 mmol) in PPA (4 g, 40 mmol). The resulting precipitate was collected by filtration, washed with water, and dried to give 2,3-dimethyl-8-(trifluoromethyl)quinolin-4-ol. Mass Spectrum (ESI) m/e=242 (M+1).
Reaction SMILES: [CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([CH2:37][CH:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[C:14](=O)[CH2:15][CH2:16][C:17]([C:19]3[N:24]=[CH:23][C:22]([CH:25]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:21][CH:20]=3)=O)=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.C([O-])(=O)C.[NH4+:48]>C(O)(=O)C.C(OCC)(=O)C>[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([C:14]3[NH:48][C:17]([C:19]4[N:24]=[CH:23][C:22]([CH:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:21][CH:20]=4)=[CH:16][CH:15]=3)[CH2:37][CH:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)=[CH:9][CH:8]=2)(=[O:5])=[O:6])[CH2:3][CH2:2]1
Reactant: [NH4+]
Reactant: CCOC(=O)C(C(=O)OCC)c1ccc(C(=O)CCC(=O)C(CC2CCOCC2)c2ccc(S(=O)(=O)C3CC3)cc2)nc1
Agent: CC(=O)[O-]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CCOC(=O)C(C(=O)OCC)c1ccc(-c2ccc(C(CC3CCOCC3)c3ccc(S(=O)(=O)C4CC4)cc3)[nH]2)nc1
Temperature: 110 °C
Reaction time: 0.67 h
Yield: 82.6 %

Procedure:
To a solution (5 mL) of diethyl (6-{5-[4-(cyclopropylsulfonyl)phenyl]-4-oxo-6-(tetrahydro-2H-pyran-4-yl)hexanoyl}pyridin-3-yl)malonate (150 mg) in acetic acid was added ammonium acetate (300 mg), and the mixture was stirred at 110° C. for 40 min. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and washed with water. The ethyl acetate layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (120 mg, yield 83%) was obtained as a colorless amorphous solid from a fraction eluted with ethyl acetate-hexane (1.5:1, volume ratio). MS: 595 (MH+).
Reaction SMILES: Br[CH:2]1[C:7]2=[N:8][CH:9]=[C:10]([C:13]([OH:15])=[O:14])[C:11](=[O:12])[N:6]2[CH:5]([CH3:16])[CH2:4][CH2:3]1.C(#N)C.[NH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O>[NH:20]([CH:2]1[C:7]2=[N:8][CH:9]=[C:10]([C:13]([OH:15])=[O:14])[C:11](=[O:12])[N:6]2[CH:5]([CH3:16])[CH2:4][CH2:3]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: CC1CCC(Br)c2ncc(C(=O)O)c(=O)n21
Reactant: Nc1ccccc1
Solvent: O
Solvent: CC#N
Product: CC1CCC(Nc2ccccc2)c2ncc(C(=O)O)c(=O)n21
Temperature: 25 °C
Reaction time: 48 h
Yield: 86.11 %

Procedure:
148.7 g. (0.50 mole) of 9-bromo-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid are dissolved in 250 ml. of acetonitrile and 100 ml. of aniline are further added. The solution is stirred for 2 days in a nitrogen gas atmosphere at room temperature. 1000 ml. of water is added and the mixture is stirred for a further half an hour. The crystals are filtered and washed with water and finally reboiled in 1400 ml. of methanol. 128.8 g. (86.11%) of 9-anilino-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid are obtained. Melting point: 198°-199° C.
Reaction SMILES: [Cl:1][C:2]1[CH:23]=[CH:22][C:5]2[O:6][C:7]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:8]=3[CH:9]([N:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)[CH2:10][C:4]=2[CH:3]=1.Cl[CH2:25][CH2:26][N:27]1[CH2:31][CH2:30][O:29][C:28]1=[O:32]>>[Cl:1][C:2]1[CH:23]=[CH:22][C:5]2[O:6][C:7]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:8]=3[CH:9]([N:11]3[CH2:16][CH2:15][N:14]([CH2:25][CH2:26][N:27]4[CH2:31][CH2:30][O:29][C:28]4=[O:32])[CH2:13][CH2:12]3)[CH2:10][C:4]=2[CH:3]=1
Reactant: O=C1OCCN1CCCl
Reactant: Fc1ccc2c(c1)C(N1CCNCC1)Cc1cc(Cl)ccc1O2
Product: O=C1OCCN1CCN1CCN(C2Cc3cc(Cl)ccc3Oc3ccc(F)cc32)CC1

Procedure:
1-[2-chloro-8-fluoro-10,11-dihydro-dibenz[b,f]oxepin-10-yl]-piperazine is reacted with 3-(2-chloro-ethyl)-2-oxazolidinone in the manner described in Example 1, and there is obtained 3-[2-{4-[2-chloro-8-fluoro-10,11-dihydro-dibenz[b,f]oxepin-10-yl]-1-piperazinyl}-ethyl]-2-oxazolidinone as an oil. The maleate, prepared in acetone, melts at 180°-182° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([NH2:19])[CH:14]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[O-:20][C:21]#[N:22].[K+].OP(O)(O)=O>O.C(O)(=O)C>[C:1]([O:5][C:6]([NH:8][CH:9]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([NH:19][C:21]([NH2:22])=[O:20])[CH:14]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: N#C[O-]
Reactant: CC(C)(C)OC(=O)NC(C(=O)O)c1cccc(N)c1
Agent: O=P(O)(O)O
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: CC(C)(C)OC(=O)NC(C(=O)O)c1cccc(NC(N)=O)c1

Procedure:
A solution of α-t-butoxycarbonylamino-m-aminophenylacetic acid (2.66 g, 0.01 mol) and potassium cyanate (0.81 g, 0.01 mol) in a mixture of water (35 ml) and acetic acid (2.5 ml) was heated at 56° for 3 hours. The solution was cooled, acidified with 40% H3PO4, and extracted with ethyl acetate. The dried extracts were evaporated to give the title product: mp 93°-95° (dec).
Reaction SMILES: C1(C(=[N:14][CH:15]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[C:16]#[N:17])C2C=CC=CC=2)C=CC=CC=1.[ClH:26].O>C1COCC1>[ClH:26].[NH2:14][CH:15]([CH2:18][C:19]1[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=1)[C:16]#[N:17]
Reactant: N#CC(Cc1ccc(F)cc1)N=C(c1ccccc1)c1ccccc1
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Product: N#CC(N)Cc1ccc(F)cc1
Reaction time: 3 h
Yield: 93 %

Procedure:
To a solution of 2-(diphenylmethyleneamino)-3-(4-fluorophenyl)propanenitrile (1.65 g, 5.02 mmol, 1.0 equiv) in THF (20.1 mL) was added HCl (5.53 mL of a 1 M aqueous solution, 5.53 mmol, 1.1 equiv). After stirring 3 h, the reaction was poured into water and washed with ether (×3). The aqueous layer was neutralized by the addition of 10 M NaOH and extracted with CH2Cl2 (×3). The combined CH2Cl2 extracts were dried (Na2SO4) and then concentrated in vacuo to provide the title compound (0.77 g, 93% yield) as a colorless oil. For convenience, the amine could be converted into the hydrochloride salt by dissolution in ether, treating with 2 M HCl in ether, and filtering the resulting white solid: 1H NMR (400 MHz, CDCl3) δ ppm 7.24-7.29 (m, 2H), 7.01-7.08 (m, 2H), 3.85-3.96 (m, 1H), 2.92-3.07 (m, 2H), 1.60 (d, J=7.55 Hz, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:15]2[CH:16]=[CH:17][C:18]3[C:22]4[CH:23]=[CH:24][C:25]([C:27]5[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=5[C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)=[CH:26][C:21]=4[S:20][C:19]=3[CH:41]=2)=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:8]=1.CO>ClCCl.[Fe](Cl)(Cl)Cl>[CH3:34][O:33][C:30]1[CH:29]=[C:28]2[C:27](=[CH:32][CH:31]=1)[C:25]1[C:24](=[CH:23][C:22]3[C:18]4[CH:17]=[C:16]5[C:15](=[CH:41][C:19]=4[S:20][C:21]=3[CH:26]=1)[C:6]1[C:7](=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[C:9]1[C:14]5=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:40]1[C:35]2=[CH:36][CH:37]=[CH:38][CH:39]=1
Reactant: COc1ccc(-c2ccc3c(c2)sc2cc(-c4ccc(OC)cc4-c4ccccc4)ccc23)c(-c2ccccc2)c1
Agent: Cl[Fe](Cl)Cl
Solvent: ClCCl
Solvent: CO
Product: COc1ccc2c(c1)c1ccccc1c1cc3c(cc21)sc1cc2c4ccc(OC)cc4c4ccccc4c2cc13
Reaction time: 1 h
Yield: 92.6 %

Procedure:
In a 1000 ml three-necked flask that had been deaerated and filled with nitrogen, 4.4 g (8.1 mmol) of 3,7-bis(5-methoxybiphenyl-2-yl)dibenzo[b,d]thiophene was dissolved in anhydrous dichloromethane (400 ml), 13.2 g (81 mmol) iron(III)chloride was then added, and the mixture was stirred one hour. Methanol 200 ml were added to the mixture and the organic layer was separated and the solvent removed in vacuum. The residue was purified by column chromatography on silica(hexane-dichloromethane) afforded a white solid (4.1 g, 7.5 mmol, 93%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1.[N+:23]([C:26]1[CH:27]=[C:28]([N:32]=[C:33]=[O:34])[CH:29]=[CH:30][CH:31]=1)([O-:25])=[O:24]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:17]=[CH:18][C:19]([NH:22][C:33]([NH:32][C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([N+:23]([O-:25])=[O:24])[CH:27]=2)=[O:34])=[CH:20][CH:21]=1
Reactant: O=C=Nc1cccc([N+](=O)[O-])c1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=O)Nc4cccc([N+](=O)[O-])c4)cc3)c2cc1OC
Yield: 34.1 %

Procedure:
6,7-Dimethoxy-4-(4-aminophenoxy)quinoline (83 mg) was dissolved in toluene (6 ml) with heat, 3-nitrophenyl isocyanate (384 mg) was added, and the admixture was refluxed with heat for 40 minutes. The resulting residue was purified by column chromatography on silica gel eluting with chloroform/acetone (10/1) to obtain 44 mg of the title compound (yield: 34%).
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.[CH2:7](O)[CH2:8][O:9][CH2:10][CH2:11]O.P(=O)(O)(O)O.[OH-].[Na+]>CS(C)=O.C1(C)C=CC=CC=1>[O:9]([CH2:10][CH2:11][N:3]1[CH:4]=[CH:5][N:6]=[C:2]1[CH3:1])[CH2:8][CH2:7][N:3]1[CH:4]=[CH:5][N:6]=[C:2]1[CH3:1]
Reactant: OCCOCCO
Reactant: Cc1ncc[nH]1
Agent: O=P(O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: CS(C)=O
Product: Cc1nccn1CCOCCn1ccnc1C
Reaction time: 16 h

Procedure:
2-Methyl imidazole (279 g; 3.4 moles), diethylene glycol (159 g; 1.5 mole), toluene (30 g), and 85% phosphoric acid (20 g; 0.17 mole) were charged in a flask equipped with a stirrer, a thermometer, and a distillation column, and the mixture was stirred at 240°~250° C. for 16 hours. Water produced during that time was distilled out by azeotropic distillation with toluene, and after fractionation the toluene was reflexed. The resulting product was incorporated with an aqueous solution of 48% sodium hydroxide (28.8 g; 0.35 mole) and subjected to distillation under reduced pressure of 1 mm Hg at 210°~215° C. to give a fraction of 239 g (yield, 68% based on diethylene glycol). Total amine value: 465 (theoretical value: 479). 'H--NMR (DMSO--d6, δppm)
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]([C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)[CH:5]=[C:6]([C:8]2[C:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:10][O:11][C:12]=2[CH3:13])[N:7]=1.[O-:29][CH2:30][CH3:31].[Na+]>C(O)C.CO>[CH2:30]([O:29][CH2:2][C:3]1[N:4]([C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)[CH:5]=[C:6]([C:8]2[C:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:10][O:11][C:12]=2[CH3:13])[N:7]=1)[CH3:31]
Reactant: Cc1onc(-c2ccccc2)c1-c1cn(-c2ccc([N+](=O)[O-])cc2)c(CCl)n1
Reactant: CC[O-]
Agent: [Na+]
Solvent: CO
Solvent: CCO
Product: CCOCc1nc(-c2c(-c3ccccc3)noc2C)cn1-c1ccc([N+](=O)[O-])cc1
Yield: 92 %

Procedure:
As described for Example 150, 4-[2-chloromethyl-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazole (50 mg, 0.13 mmol), using sodium ethoxide in ethanol instead of sodium methoxide in methanol, was converted to the title compound (47 mg, 92%) which was obtained as a yellow solid. MS: m/e=405.5 [M+H]+.