Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[OH-].[Na+].[C:16](OC(=O)C)(=[O:18])[CH3:17].Cl>O>[C:16]([NH:1][C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1)(=[O:18])[CH3:17]
Reactant: N[C@@H](Cc1ccc(O)cc1)C(=O)O
Reactant: CC(=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O
Temperature: 0 °C
Reaction time: 0.75 h

Procedure:
To a solution of (−) tyrosine (2.50 g, 13.8 mmol) in NaOH (aq) (2 N, 7.59 mL, 15.2 mmol) was added H2O (6 mL). This vigorously stirred solution was cooled to 0° C., and acetic anhydride (3.25 mL, 3.52 g, 34.5 mmol) was added via syringe pump over 30 min. During this addition, excess NaOH (aq) (2 N, 34.5 mL, 69.0 mmol) was added in 10 portions. After the addition was complete, the reaction was warmed to room temperature and stirred for 45 min. The colorless solution was then carefully acidified to pH 2 with 6 N HCl (aq). After concentrating under reduced pressure, the resulting solid was extracted with 15% H2O in acetone (4×). The filtrate was concentrated under reduced pressure to afford a slightly yellow oil. The addition of H2O (1.5 mL) afforded N-acetyl tyrosine as a white precipitate (670 mg, 3.00 mmol, 22%) that was washed with H2O (3×). The washings were saved for later precipitations. To a solution of N-acetyl tyrosine (76 mg, 0.34 mmol) in NaOH (aq) (0.5 N, 0.61 mL, 0.31 mmol) was added K2HPO4 (aq) (1 M, 0.61 mL, 0.61 mmol). This vigorously stirred solution was cooled to 0° C., and cyclohexyl isocyanate (48 μL, 47 mg, 0.37 mmol) was added dropwise to the reaction. During the addition, 0.5 M NaOH (aq) (4 drops) was added to maintain the pH between pH 8 and 9. After the addition was complete, the reaction was warmed to rt and stirred for 3 h. A white precipitate had formed, and the resulting suspension was washed with Et2O (2×). The aqueous layer was separated and carefully acidified to pH 2 with 6 N HCl (aq). The desired product xxx precipitated as a white solid (89 mg, 0.26 mmol, 76%) that was filtered and washed with H2O (3×).
Reaction SMILES: F[C:2](F)(F)[C:3](O)=[O:4].[NH2:8][CH2:9][CH:10]1[O:14][C:13](=[O:15])[N:12]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[S:23][CH:24]([CH3:29])[C:25](=[O:28])[NH:26][N:27]=3)=[C:18]([F:30])[CH:17]=2)[CH2:11]1.C(OC(=O)C)(=O)C>N1C=CC=CC=1>[F:30][C:18]1[CH:17]=[C:16]([N:12]2[CH2:11][C@H:10]([CH2:9][NH:8][C:3](=[O:4])[CH3:2])[O:14][C:13]2=[O:15])[CH:21]=[CH:20][C:19]=1[C:22]1[S:23][C@@H:24]([CH3:29])[C:25](=[O:28])[NH:26][N:27]=1
Reactant: CC1SC(c2ccc(N3CC(CN)OC3=O)cc2F)=NNC1=O
Reactant: O=C(O)C(F)(F)F
Solvent: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)NC[C@H]1CN(c2ccc(C3=NNC(=O)[C@H](C)S3)c(F)c2)C(=O)O1
Temperature: 25 °C
Reaction time: 4 h
Yield: 76 %

Procedure:
2-[4-(5-Aminomethyl-2-oxo-oxazolidin-3-yl)-2-fluorophenyl]-6-methyl-4H-[1,3,4]thiadiazin-5-one, trifluoroacetate salt is dissolved in pyridine (2 ml) and acetic anhydride (0.0163 ml, 0.173 mmol) is added. The reaction is stirred at room temperature for 4 hours and then evaporated to dryness. The residue is purified by PTLC (10% MeOH/DCM) to give pure product as a white solid (0.046 g, 76%); 1HNMR (300 MHz, DMSO-d6) δ 1.34 (d, J=7.1 Hz, 3H), 1.82 (s, 3H), 3.41 (t, J=5.5, 2H), 3.71-3.82 (m, 2H), 4.14 (t, J=9.3 Hz, 1H), 4.71-4.79 (m, 1H), 7.41 (dd, J=1.9, 8.8 Hz, 1H), 7.58 (dd, J=1.7, 14, 1H), 7.68 (t, J=8.5, 1H), 8.25 (t, J=5.5 Hz, 1H), 11.7 (s, 1H); mp 200-2; MS (m/z): [M+H]+=381.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:10][C@H:11]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=1)[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:41][CH2:42][F:43]>CN(C)C=O>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:10][C@H:11]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:41][CH2:42][F:43])=[CH:22][CH:21]=1)[C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: FCCBr
Reactant: CC(C)(C)OC(=O)N[C@@H](C[C@H](Cc1ccc(O)cc1)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N[C@@H](C[C@H](Cc1ccc(OCCF)cc1)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Temperature: 60 °C
Reaction time: 8 h

Procedure:
To 315 mg (0.68 mmol) of di-tert-butyl (4S)—N-(tert-butoxycarbonyl)-4-(4-hydroxy-benzyl)-L-glutamate in 30 mL N,N-dimethylformamide were added 206 mg (1.5 mmol) of powdered potassium carbonate and 104 mg (0.81 mmol) of 1-bromo-2-fluoroethane and the resulting suspension was stirred for 5 h at 60° C. and overnight at room temperature. The reaction mixture was then filtered, the solvent evaporated and the residue was taken up in ethyl acetate and water. The organic phase was separated off, washed with water until neutral, dried over sodium sulfate and filtered, and the filtrate was concentrated in vacuo. Di-tert-butyl (4S)—N-(tert-butoxycarbonyl)-4-[4-(2-fluoroethoxy)benzyl]-L-glutamate was obtained as crude product (110 mg, 32.6%) and deprotected without further purification: 3 mL of trifluoro acetic acid were added to the oily residue and the solution was stirred for 2 days at room temperature. The excess of trifluoro acetic acid was evaporated and the residue was taken up three times in tetrahydrofuran and than evaporated. The resulting oil was chromatographed on C-18 reversed phase silica gel using a water/acetonitrile gradient, the appropriate fractions were combined and concentrated.
Reaction SMILES: [C:1]([CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([CH2:13][S:14]([NH:17][CH3:18])(=[O:16])=[O:15])[CH:11]=2)[NH:6][CH:5]=1)#[N:2].[H-].[Na+].[CH2:21](Cl)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN(C)C=O>[C:1]([CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([CH2:13][S:14]([NH:17][CH3:18])(=[O:16])=[O:15])[CH:11]=2)[N:6]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:5]=1)#[N:2]
Reactant: ClCc1ccccc1
Reactant: CNS(=O)(=O)Cc1ccc2[nH]cc(CC#N)c2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CNS(=O)(=O)Cc1ccc2c(c1)c(CC#N)cn2Cc1ccccc1
Temperature: -30 °C
Reaction time: 1 h
Yield: 22.6 %

Procedure:
3-(Cyanomethyl)-N-methyl-1H-indole-5-methanesulphonamide (0.4 g) was dissolved in re-distilled dimethylformamide (10 ml) and treated with sodium hydride (0.132 g, 80% dispersion in oil). After 0.5 h the stirred suspension was cooled to -30° C. and treated with distilled benzyl chloride (0.19 g). The mixture was allowed to warm to 10°, stirred for 1 h and then poured onto ice (10 g). The suspension was filtered, and the solid collected and washed with water (20 ml) and cyclohexane (30 ml). The solid was purified by chromatography (M) and the appropriate fractions were combined and concentrated in vacuo to 20 ml, whereupon a solid crystallised out which was collected and dried to give the title compound (0.12 g), m.p. 133°-135°. T.l.c. (M), Rf 0.4, (KMnO4)
Reaction SMILES: CS(OCCCCO[C:11]1[CH:12]=[CH:13][C:14]2[NH:19][C:18](=[O:20])[O:17][C:16]([CH3:22])([CH3:21])[C:15]=2[CH:23]=1)(=O)=O.[CH3:24][C:25]1[CH:30]=[CH:29][C:28]([SH:31])=[CH:27][CH:26]=1>>[CH3:24][C:25]1[CH:30]=[CH:29][C:28]([S:31][CH2:13][CH2:14][CH2:15][CH2:16][O:17][C:12]2[CH:11]=[CH:23][C:15]3[C:16]([CH3:21])([CH3:22])[O:17][C:18](=[O:20])[NH:19][C:14]=3[CH:13]=2)=[CH:27][CH:26]=1
Reactant: Cc1ccc(S)cc1
Reactant: CC1(C)OC(=O)Nc2ccc(OCCCCOS(C)(=O)=O)cc21
Product: Cc1ccc(SCCCCOc2ccc3c(c2)NC(=O)OC3(C)C)cc1

Procedure:
Prepared analogously to Example 210 from 6-(4-methanesulfonyloxy-butoxy)-4,4-dimethyl-4H-3,1-benzoxazin-2-one and 4-methyl-thiophenol.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[C:7](=O)[C:6]([CH2:19][CH2:20][CH2:21][CH3:22])([CH2:13][CH2:14][C:15](=[O:18])[CH2:16][CH3:17])[CH2:5]2.C(O)(=O)C.Cl.C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:1][C:2]1[CH:3]=[C:4]2[C:8]([C:7]3[C:6]([CH2:19][CH2:20][CH2:21][CH3:22])([CH2:5]2)[CH2:13][CH2:14][C:15](=[O:18])[C:16]=3[CH3:17])=[CH:9][C:10]=1[F:11]
Reactant: CCCCC1(CCC(=O)CC)Cc2cc(N)c(F)cc2C1=O
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: CCCCC12CCC(=O)C(C)=C1c1cc(F)c(N)cc1C2
Temperature: 100 °C
Yield: 80.5 %

Procedure:
The diketone from step 1 (0.51 g, 1.73 mmol) was treated with acetic acid (5 mL,) and aqueous 6N HCl (5 mL). The resulting solution was stirred and heated in an oil bath at 100° C. for 1.5 hours. After cooling to room temperature, the mixture was poured into a slurry of solid NaHCO3 in CH2Cl2, then filtered through a pad of silica gel and the product was washed off with EtOAc. The filtrate and washings were concentrated under vacuum. The residue was purified by flash chromatography on a Biotage 40M KP-Sil column, eluting with 4:1 to 3:1 hexanes-EtOAc. The product containing fractions were evaporated under vacuum to provide 7-amino-9a-butyl-6-fluoro-4-methyl-1,2,9,9a-tetrahydro-3H-fluoren-3-one (0.40 g, 83%) as a yellow solid
Reaction SMILES: [NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][C:2]1=[O:3].[C:12]1(=[O:17])[O:16][CH2:15][CH2:14][CH2:13]1>>[OH:17][CH2:12][CH2:13][CH2:14][C:15]([C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[NH:1][C:2](=[O:3])[CH2:4][CH2:5]2)=[O:16]
Reactant: O=C1CCCO1
Reactant: O=C1CCc2ccccc2N1
Product: O=C1CCc2cc(C(=O)CCCO)ccc2N1
Temperature: 0 °C
Reaction time: 10 h

Procedure:
14.4 Grams of 3,4-dihydrocarbostyril and 10 g of γ-butyrolacton were mixed into 120 g of polyphosphoric acid and stirred at 80°-90° C. for 10 hours. The reaction mixture was poured into 300 ml of ice-water and was allowed to stand overnight. Then the precipitates thus formed were collected by filtration and washed with water, then recrystallized from ethanol-ethyl acetate to obtain 9.5 g of 6-(4-hydroxy-1-oxobutyl)-3,4-dihydrocarbostyril, having the melting point of 175°-176° C. in colorless prism-like crystals. Next, 5 g of 6-(4-hydroxy-1-oxobutyl)-3,4-dihydrocarbostyril and 0.5 g of palladium black were mixed in 160 ml of ethanol and the mixture was subjected to catalytic reduction under 3 kg/cm2 of hydrogen gas at 60° C. for 6 hours. The reaction mixture was then cool and was added 1 ml of concentrated hydrochloric acid thereinto. Further the reaction mixture was subjected to the catalytic reduction under 3 kg/cm2 of hydrogen gas for 6 hours. The reaction mixture was filtered and the mother liquor was concentrated under a reduced pressure. The residue was recrystallized from ligroin to obtain 3.2 g of 6-(4-hydroxybutyl)-3,4-dihydrocarboxtryril, having the melting point of 133°-134° C. Next, 3.2 g of 6-(4-hydroxybutyl)-3,4-dihydrocarbostyril and 5 ml of thionyl chloride were mixed into 50 ml of chloroform and the mixture was stirred at a room temperature for 24 hours. The reaction mixture was concentrated under a reduced pressure. The residue was then recrystallized from ligroin to obtain 1.8 g of 6 -(4-chlorobutyl)-3,4-dihydrocarbostryl, having the melting point of 119°-121° C., in colorless prism-like crystals.
Reaction SMILES: CS[C:3]1[NH:12][C:11](=[O:13])[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[N:4]=1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)=[CH:17][CH:16]=1>C(O)CC(C)C>[Cl:14][C:15]1[CH:16]=[CH:17][C:18]([N:21]2[CH2:26][CH2:25][N:24]([C:3]3[NH:12][C:11](=[O:13])[C:10]4[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=4[N:4]=3)[CH2:23][CH2:22]2)=[CH:19][CH:20]=1
Reactant: Clc1ccc(N2CCNCC2)cc1
Reactant: CSc1nc2c(c(=O)[nH]1)CCCC2
Solvent: CC(C)CCO
Product: O=c1[nH]c(N2CCN(c3ccc(Cl)cc3)CC2)nc2c1CCCC2

Procedure:
2-Methylsulfanyl-5,6,7,8-tetrahydro-3H-quinazolin-4-one (100 mg; 0.51 mmol) and 1-(4-chlorophenyl)piperazine (100.2 mg; 0.51 mmol) are reacted in isoamyl alcohol (1 ml) in accordance with the procedure for Example 1 and worked up; yield: 83 mg (47%), crystals;
Reaction SMILES: [Br:1][C:2]1[C:7]2[C:8](=[O:26])[N:9]3[CH2:25][CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([N:18]3C=CN=C3)=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.N.O>CN(C)C=O>[Br:1][C:2]1[C:7]2[C:8](=[O:26])[N:9]3[CH2:25][CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([NH2:18])=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: O=C1c2c(Br)cccc2-n2cnc(C(=O)n3ccnc3)c2[C@@H]2CCCN12
Agent: N
Solvent: O
Solvent: CN(C)C=O
Product: NC(=O)c1ncn2c1[C@@H]1CCCN1C(=O)c1c(Br)cccc1-2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A suspension of 8.8 g (21.3 mmol) of 1-[[(S)-8-bromo-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-1-yl]carbonyl]imidazole in 20 ml of N,N-dimethylformamide is treated with 3.6 ml (about 47 mmol) of a 25 percent aqueous ammonia solution and the mixture is stirred at room temperature for 1 hour. The mixture is then poured into 100 ml of water, the product is filtered off under suction after 15 minutes, rinsed with water and dried at 80° in a high vacuum. There is obtained (S)-8-bromo-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxamide of decomposition point 296°.
Reaction SMILES: Cl.[NH2:2][OH:3].[Cl:4][C:5]1[CH:6]=[C:7]([C:12]2([C:26]([F:29])([F:28])[F:27])[O:16][N:15]=[C:14]([C:17]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[C:19]([CH3:25])[CH:18]=3)[CH2:13]2)[CH:8]=[C:9]([Cl:11])[CH:10]=1.C(N(CC)CC)C>C(O)C.C(OCC)(=O)C>[Cl:4][C:5]1[CH:6]=[C:7]([C:12]2([C:26]([F:27])([F:29])[F:28])[O:16][N:15]=[C:14]([C:17]3[CH:24]=[CH:23][C:20]([C:21]([NH:2][OH:3])=[NH:22])=[C:19]([CH3:25])[CH:18]=3)[CH2:13]2)[CH:8]=[C:9]([Cl:11])[CH:10]=1
Reactant: NO
Reactant: Cc1cc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)ccc1C#N
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: CCO
Product: Cc1cc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)ccc1C(=N)NO
Temperature: 85 °C

Procedure:
Hydroxylamine hydrochloride (0.27 g) was added to a solution of 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzonitrile (1.1 g) (Example I4) and triethylamine (0.65 ml) in ethanol (30 ml). The reaction mixture was heated to 85° C. for 20 hours. The reaction mixture was allowed to cool to ambient temperature before adding more hydroxylamine hydrochloride (0.078 g). The reaction mixture was again heated to 85° C. for 3 hours. The reaction mixture was allowed to cool to ambient temperature, diluted with ethyl acetate, washed with water, dried over sodium sulfate, and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 2:1) to give Compound No. A1 of Table A (0.84 g) as a white solid.
Reaction SMILES: [Br-].[CH2:2]([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.C1CCN2C(=NCCC2)CC1.[CH2:39]([O:46][C:47]1[CH:48]=[C:49]2[C:53](=[CH:54][CH:55]=1)[N:52]([CH3:56])[C:51]([CH:57]=O)=[CH:50]2)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(#N)C>[CH2:39]([O:46][C:47]1[CH:48]=[C:49]2[C:53](=[CH:54][CH:55]=1)[N:52]([CH3:56])[C:51]([CH:57]=[CH:2][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1)=[CH:50]2)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1
Reactant: Cn1c(C=O)cc2cc(OCc3ccccc3)ccc21
Reactant: c1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Br-]
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: Cn1c(C=Cc2ccccc2)cc2cc(OCc3ccccc3)ccc21
Reaction time: 0.17 h
Yield: 34.6 %

Procedure:
Under N2, to a suspension of benzyltriphenylphosphonium bromide (980 mg, 2.26 mmol) in acetonitrile (10 ml) was added DBU at room temperature. After stirring for 10 min., 5-(benzyloxy)-1-methyl-1H-indole-2-carbaldehyde (500 mg, 1.88 mmol) was added and the mixture was stirred overnight at room temperature. The resulting mixture was filtered and washed with acetonitrile. The filtrate was concentrated in vacuo and then the residue was purified by silica gel (70 g) chromatography eluted with chloroform to give 5-(benzyloxy)-1-methyl-2-(2-phenylethenyl)-1H-indole (221 mg, 34.5%).
Reaction SMILES: [H-].[Na+].[C:3]([C:5]1[CH:24]=[CH:23][C:8]([CH2:9][CH:10]([C:17]([O:19][CH2:20][CH:21]=[CH2:22])=[O:18])[C:11]([O:13][CH2:14][CH:15]=[CH2:16])=[O:12])=[CH:7][CH:6]=1)#[N:4].Br[CH2:26][CH2:27][C:28]1[CH:37]=[CH:36][C:31]([C:32]([O:34][CH3:35])=[O:33])=[CH:30][CH:29]=1.O>CN(C=O)C>[C:3]([C:5]1[CH:6]=[CH:7][C:8]([CH2:9][C:10]([CH2:26][CH2:27][C:28]2[CH:37]=[CH:36][C:31]([C:32]([O:34][CH3:35])=[O:33])=[CH:30][CH:29]=2)([C:11]([O:13][CH2:14][CH:15]=[CH2:16])=[O:12])[C:17]([O:19][CH2:20][CH:21]=[CH2:22])=[O:18])=[CH:23][CH:24]=1)#[N:4]
Reactant: C=CCOC(=O)C(Cc1ccc(C#N)cc1)C(=O)OCC=C
Reactant: COC(=O)c1ccc(CCBr)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: C=CCOC(=O)C(CCc1ccc(C(=O)OC)cc1)(Cc1ccc(C#N)cc1)C(=O)OCC=C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 44634.3 %

Procedure:
7.13 g (178.36 mmol) of sodium hydride are added in portions to a solution of 48.53 g (162.14 mmol) of diallyl 2-(4-cyanobenzyl)malonate from Example 70A in 180 ml of DMF at 0° C. The reaction solution is then allowed to reach room temperature and is stirred for 30 min. The reaction solution is then cooled to 0° C. again and, after addition of 55 g (194.57 mmol) of methyl 4-(2-bromoethyl)benzoate [CAS 136333-97-6] in 195 ml of DMF, stirred at this temperature for 30 min. The mixture is then stirred at room temperature overnight. Water is added dropwise to the reaction mixture, which is then extracted three times with ethyl acetate, and the combined organic phases are washed with saturated sodium chloride solution and dried over sodium sulfate. After filtration, the solvent is concentrated to dryness in vacuo. The resulting crude product is purified by flash chromatography on silica gel (mobile phase: petroleum ether/ethyl acetate 10:1). 33.4 g (72.37 mol, 44% yield) of a colorless solid are obtained.
Reaction SMILES: [C@H:1]1([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[N+:21]([O-])=O)[N:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[H][H]>C(O)C.[Pd]>[C@H:1]1([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[C:17]([NH2:21])=[CH:16][CH:15]=[CH:14][C:13]=3[N:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1
Reactant: O=[N+]([O-])c1cccc2nc(N[C@@H]3CCc4ccccc43)ccc12
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: Nc1cccc2nc(N[C@@H]3CCc4ccccc43)ccc12

Procedure:
(R)-Indan-1-yl-(5-nitro-quinolin-2-yl)-amine (2.66 g, 8.7 mmol) was dissolved in 420 mL ethanol. Palladium on charcoal (10%, 463 mg, 0.4 mmol) was added and the reaction mixture war hydrogenated with a hydrogen balloon overnight. The palladium was filtered off and the solvent was evaporated. The title compound was obtained as a brown solid (2.29 g, 95%), MS: m/e=276.3 (M+H+).
Reaction SMILES: [Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH2:11])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17](O)=[O:18].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.C(N(CC)CC)C.[Li+].[OH-]>C(Cl)Cl.O>[Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH:11][C:17](=[O:18])[C:16]3[CH:20]=[CH:21][CH:22]=[C:14]([CH3:13])[CH:15]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: Nc1c[nH]c2ncc(Br)c(F)c12
Reactant: Cc1cccc(C(=O)O)c1
Agent: O=C1OCCN1P(=O)(Cl)N1CCOC1=O
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1cccc(C(=O)Nc2c[nH]c3ncc(Br)c(F)c23)c1
Reaction time: 0.17 h
Yield: 55.3 %

Procedure:
5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (0.250 g, 1.09 mmol), 3-methylbenzoic acid (311 mg, 2.28 mmol), BOP-Cl (581 mg, 2.28 mmol), and triethylamine (0.757 mL, 5.43 mmol) in DCM (5 mL) were stirred at room temperature for 30 minutes. 3M LiOH (3 mL) was then added. The reaction was stirred for an additional 10 minutes and then poured into water. The mixture was then filtered, washed with DCM, washed with 10:1 DCM:MeOH and dried to give N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-methylbenzamide (210 mg, 55.5% yield) as a solid.
Reaction SMILES: [F:1][C:2]([F:25])([F:24])[C:3]1[CH:23]=[CH:22][C:6]([C:7]([C:9]2[N:13]([CH3:14])[C:12]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:11][C:10]=2[CH3:21])=[O:8])=[CH:5][CH:4]=1.Cl[C:27]1C=CC(C(C2N(C)C(CC(OCC)=O)=CC=2C)=O)=CC=1>>[F:25][C:2]([F:1])([F:24])[C:3]1[CH:4]=[CH:5][C:6]([C:7]([C:9]2[N:13]([CH3:14])[C:12]([CH:15]([CH3:27])[C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:11][C:10]=2[CH3:21])=[O:8])=[CH:22][CH:23]=1
Reactant: CCOC(=O)Cc1cc(C)c(C(=O)c2ccc(C(F)(F)F)cc2)n1C
Reactant: CCOC(=O)Cc1cc(C)c(C(=O)c2ccc(Cl)cc2)n1C
Product: CCOC(=O)C(C)c1cc(C)c(C(=O)c2ccc(C(F)(F)F)cc2)n1C

Procedure:
The methylation procedure of Example 77A is repeated, except that an equivalent quantity of ethyl 5-(p-trifluoromethylbenzoyl)-1,4-dimethylpyrrole-2-acetate (from Example 89) is methylated instead of the ethyl 5-(p-chlorobenzoyl)-1,4-dimethylpyrrole-2-acetate used in Example 77A, to yield ethyl 5-(p-trifluoromethylbenzoyl)-1,4,α-trimethylpyrrole-2-acetate.
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8]Br)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:12]1([P:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>O1CCCC1>[N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8][PH:18]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: O=[N+]([O-])c1ccc(CBr)cc1
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccc(C[PH](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Temperature: 75 °C
Yield: 44.9 %

Procedure:
In an embodiment of the invention, a method for preparing the aforesaid alignment film in a laboratory level is illustrated as an example. 10 g of 4-nitrobenzyl bromide is mixed with 12 g of triphenylphosphine and dissolved in 150 ml of a dry tetrahydrofuran solution, heated to 75° C. and agitated under reflux for 48 hours, to obtain 8.2 g of a dry white p-nitrobenzyl triphenylphosphine. The p-nitrobenzyl triphenylphosphine is mixed with 2.6 g of p-nitrobenzaldehyde in a 150 ml tetrahydrofuran solution, and agitated under room temperature for about 24 hours to obtain 4.2 g of p-nitrostilbene. The resultant p-nitrostilbene is mixed with 14.7 g of tin dichloride, dissolved in a mixed solution of 30 ml/40% hydrochloride acid and 100 ml acetone, agitated under the room temperature for about 2 hours and refluxed for 8 hours to obtain p-aminostilbene. The p-aminostilbene is mixed with 9,9′-bianthracyl tetracarboxylic dianhydride in a dry NMP (N-methyl-pyrrolidone) solution under agitation for 24 hours, under protection of nitrogen gas, to obtain the precursor of the polyimide alignment film involved in the embodiment. The precursor is heated to 230° C. to obtain the final alignment film, which is a light sensitive alignment film.
Reaction SMILES: O[C:2]1[C:11]([CH:12]([CH:15]=[CH2:16])[CH2:13][OH:14])=[CH:10][C:9]([CH3:17])=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](=[O:18])[NH:7]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)Cl.Cl>N1C=CC=CC=1.CO>[CH3:17][C:9]1[CH:10]=[C:11]2[CH:12]([CH:15]=[CH2:16])[CH2:13][O:14][C:2]2=[C:3]2[C:8]=1[NH:7][C:6](=[O:18])[CH:5]=[CH:4]2
Reactant: C=CC(CO)c1cc(C)c2[nH]c(=O)ccc2c1O
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CO
Solvent: ClC(Cl)(Cl)Cl
Solvent: c1ccncc1
Product: C=CC1COc2c1cc(C)c1[nH]c(=O)ccc21
Temperature: 60 °C
Reaction time: 3 h
Yield: 95.9 %

Procedure:
5-Hydroxy-6-(2-hydroxy-1-vinylethyl)-8methylcarbostyril (7.2 g) was dissolved in pyridine (50 ml), to which triphenylphosphine (25.0 g) and carbon tetrachloride (15 ml) were added in this order, followed by stirring at 60° C. for 3 hours. Methanol (50 ml) was added thereto and stirred for 1 hour. The reaction mixture was filtered. The filtrate was condensed under reduced pressure, to which 1N-HCl was added. Extraction was performed with chloroform. The chloroform phase was dried, and the solvent was evaporated. The residue was recrystallized from a solvent mixture of chloroform-ethyl acetate-ether to obtain 6.4 g of 5-methyl-2,3,6,7-tetrahydro-3-vinylfuro[2,3-f]quinoline-7-one as colorless powdery crystals (95.9%).