Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([N+:14]([O-:16])=[O:15])=[C:9]([CH:13]=1)[C:10]([OH:12])=[O:11]>C(COC)OC>[Cl:1][C:2]1[CH:20]=[C:19]([C:21]([F:22])([F:23])[F:24])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([N+:14]([O-:16])=[O:15])=[C:9]([CH:13]=1)[C:10]([O-:12])=[O:11].[CH:2]1([NH2+:14][CH:8]2[CH2:9][CH2:13][CH2:5][CH2:6][CH2:7]2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:3]1
Reactant: O=C(O)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Solvent: COCCOC
Product: C1CCC([NH2+]C2CCCCC2)CC1
Product: O=C([O-])c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Yield: 119.8 %

Procedure:
5-(2-Chloro-4-trifluoromethylphenoxy)-2-nitrobenzoic acid (3.0 g, 0.0083 mole) is dissolved in glyme (20 ml) and dicyclohexylamino (1.64 g, 0.0091 mole) is added at room temperature while stirring. The solvent is removed in vacuo, the residue triturated with petroleum ether (bp 30°-60° C.) and dried to give 2.7 g of product, mp 197°-9° C. Anal. Calcd. for C26H30ClF3N2O5 : C, 57.51; H, 5.56; N, 5.15; Cl, 6.53; F, 10.49. Found C, 57.25; H, 5.71; N, 5.55; Cl, 6.40; F, 10.24.
Reaction SMILES: Cl[S:2]([C:5]1[CH:6]=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH3:17])=[C:9]([CH:13]=1)[C:10]([NH2:12])=[O:11])(=O)=O.S(=O)(=O)(O)O.C(O)C>[Zn].O>[CH2:15]([O:14][C:8]1[CH:7]=[CH:6][C:5]([SH:2])=[CH:13][C:9]=1[C:10]([NH2:12])=[O:11])[CH2:16][CH3:17]
Reactant: CCCOc1ccc(S(=O)(=O)Cl)cc1C(N)=O
Agent: O=S(=O)(O)O
Agent: [Zn]
Solvent: CCO
Solvent: O
Product: CCCOc1ccc(S)cc1C(N)=O
Temperature: -5 °C
Reaction time: 1.5 h

Procedure:
Finely powdered 5-chlorosulphonyl-2-propoxybenzamide (3.0 g.; prepared from the product described in Reference Example 1) was added to a mixture of concentrated sulphuric acid (12 ml.), water (25 ml.) and ethanol (25 ml.) at -20° C. The mixture was allowed to warm to -5° C. with stirring, and then powdered zinc (6 g.) was added at such a rate that the temperature did not exceed 0° C. After stirring at between -5° C. and +5° C. for 90 minutes, then at room temperature for 90 minutes, water (50 ml.) was added and the resulting dark suspension was finally heated to boiling for approximately 75 minutes, distilling off a mixture of ethanol and water. When the temperature at the distillation head reached 96° C., distillation was stopped and the residue was cooled to room temperature. The precipitated solid was then extracted with chloroform (3 × 25 ml.). The chloroform extract was filtered to remove any remaining zinc, washed with water (2 × 10 ml.) and dried over sodium sulphate. Removal of the solvent gave an off-white solid which was recrystallised from ethanol at -30° C., to give slightly impure 2-propoxy-5-mercaptobenzamide (1.3 g.). This material was sufficiently pure for use in the next stage. Purer 2-propoxy-5-mercaptobenzamide (0.8 g.), m.p. 108° - 111° C., was obtained by further recrystallisation from a small amount of ethanol (only cooling to 0° C. instead of to -30° C.).
Reaction SMILES: [CH2:1]([NH2:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[C:9]1([C:15]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[N:16]2[C:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3C3C=CC(CBr)=CC=3)=[N:19][N:18]=[N:17]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[CH:47]1([N:53]=[C:54]=[O:55])[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1>>[CH:47]1([NH:53][C:54]([N:8]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])[CH2:1][C:2]2[CH:7]=[CH:6][C:5]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[C:20]3[N:16]([C:15]([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)([C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)[N:17]=[N:18][N:19]=3)=[CH:4][CH:3]=2)=[O:55])[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1
Reactant: O=C=NC1CCCCC1
Reactant: BrCc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reactant: CCCCCCCN
Product: CCCCCCCN(Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1)C(=O)NC1CCCCC1
Yield: 88.7 %

Procedure:
Using n-heptylamine (192 mg), [[2′-[N-(triphenylmethyl)tetrazol-5-yl]-1,1′-biphenyl-4-yl]methyl] bromide (843 mg) and cyclohexyl isocyanate (230 mg), N-cyclohexyl-N′-heptyl-N′-[[2′-[N-(triphenylmethyl)tetrazol-5-yl)-1,1′-biphenyl-4-yl]methyl]urea (0.53 g) was obtained in a similar manner as in Example 5. Yield: 49%.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](S(C)(=O)=O)[C:5]([C:12]#[N:13])=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:3]=1.[NH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>COCCOC>[NH2:1][C:2]1[N:3]=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:5]([C:12]#[N:13])=[C:6]([N:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[N:7]=1
Reactant: C1CCNCC1
Reactant: CS(=O)(=O)c1nc(N)nc(-c2ccccc2)c1C#N
Solvent: COCCOC
Product: N#Cc1c(-c2ccccc2)nc(N)nc1N1CCCCC1

Procedure:
From 2-amino-4-methanesulfonyl-6-phenyl-pyrimidine-5-carbonitrile and piperidine in DME. EI-MS m/e (%): 279 (M+, 32), 278 ([M—H]+, 100).
Reaction SMILES: [CH3:1][CH:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)N1.CC1C=C[C:20]2[CH2:19][CH2:18][CH2:17][CH2:16][C:15]=2N=1.CC1CCC2C(CCCC2)N1>>[CH3:17][CH2:16][CH2:15][CH2:20][CH2:19][CH2:18][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:9][CH2:10][CH2:11][CH2:2][CH3:1]
Reactant: CC1CCc2ccccc2N1
Reactant: Cc1ccc2c(n1)CCCC2
Agent: CC1CCC2CCCCC2N1
Product: CCCCCCCCCCCCCCCC

Procedure:
The autoclave was cooled and the contents were suction filtered. Gas liquid chromatographic analysis of the colorless liquid filtrate on a 6'×1/8" 10% Carbowax 20M column at 200° C. showed that the only product of the reaction was 2-methyl-1,2,3,4-tetrahydroquinoline (96% 2-methyl-1,2,3,4-tetrahydroquinoline and 4% starting material). There were no detectable amounts of 2-methyl-5,6,7,8-tetrahydroquinoline and 2-methyldecahydroquinoline. Gas liquid chromatographic analysis with an external standard showed that the absolute yield of product based on consumed starting material was 100%. The use of cyclohexane as the solvent instead of n-hexadecane gave the same result (97% of 2-methyl-1,2,3,4-tetrahydroquinoline and 3% of 2-methylquinoline).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][OH:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][O:12][S:29]([CH3:28])(=[O:31])=[O:30])=[O:7])([CH3:3])([CH3:4])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)NCC(CO)NC(=O)OC(C)(C)C
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCC(COS(C)(=O)=O)NC(=O)OC(C)(C)C
Reaction time: 1 h

Procedure:
To a solution of 1,2-di(t-butoxycarbonylamino)-3-hydroxypropane (3 g.) and triethylamine (2 ml.) in CH2Cl2 (30 ml.) at 0° was added methanesulphonyl chloride (1.0 ml.) with stirring. Stirring at this temperature was continued for 1 hour and the mixture was then washed with water. The organic layer was separated, dried and the solvent evaporated to give 1,2-di(t-butoxycarbonylamino)-3-methanesulphonyloxypropane (2.9 g.), m.p. 94°-96°.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[C:8]([C:11]1[CH:12]=[CH:13][C:14]([NH:31][CH2:32][CH3:33])=[C:15]([N:17]=[C:18]2[N:22]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:21](=[O:30])[CH2:20][S:19]2)[CH:16]=1)(=[O:10])[CH3:9].[CH3:34]OC(OC)N(C)C>C1(C)C=CC=CC=1>[C:8]([C:11]1[CH:12]=[CH:13][C:14]([NH:31][CH2:32][CH3:33])=[C:15]([N:17]=[C:18]2[N:22]([CH2:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:21](=[O:30])[C:20](=[CH:1][N:2]3[CH2:7][CH2:6][N:5]([CH3:34])[CH2:4][CH2:3]3)[S:19]2)[CH:16]=1)(=[O:10])[CH3:9]
Reactant: CCNc1ccc(C(C)=O)cc1N=C1SCC(=O)N1Cc1ccccc1
Reactant: COC(OC)N(C)C
Reactant: CN1CCNCC1
Solvent: Cc1ccccc1
Product: CCNc1ccc(C(C)=O)cc1N=C1SC(=CN2CCN(C)CC2)C(=O)N1Cc1ccccc1
Temperature: 100 °C
Reaction time: 3 h
Yield: 78 %

Procedure:
A mixture of 1-methylpiperazine (0.22 mL, 2.0 mmol) in N,N-dimethylformamide dimethyl acetal (1.5 mL) was heated at 100° C. After 3 h, the mixture was concentrated under reduced pressure and diluted with toluene (2 cycles), and then concentrated under vacuum. Next an aliquot (80 μL) of the concentrated intermediate was added to a solution of 2-(5-acetyl-2-ethylamino-phenylimino)-3-benzyl-thiazolidin-4-one (60 mg, 0.16 mmol) in toluene (1.0 mL, anhyd). After heating at 120° C. for 1 h, the mixture was cooled, concentrated and chromatographed (silica gel, DCM to 0.2:10:89.8 DEA/MeOH/DCM) to yield the title product (61 mg, 78%) as a yellow solid. 1H-NMR (CDCl3): δ 7.66 (1H, dd), 7.58 (1H, d), 7.55 (1H, s), 7.27-7.42 (5H, m), 6.49 (1H, d), 5.11 (2H, s), 4.12 (1H, br t), 3.45 (4H, br t), 3.03 (2H, m), 2.49 (3K, s), 2.43 (4H, br t), 2.30 (3H, s), 1.02 (3H, t); MS (ESI): 478 (MH+).
Reaction SMILES: [SH:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([CH3:11])=[CH:4][N:3]=1.C([N:14](CC)CC)C.NOS(O)(=O)=O>ClCCl.O>[CH3:11][C:5]1[CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]([S:1][NH2:14])=[N:3][CH:4]=1
Reactant: Cc1cnc(S)c([N+](=O)[O-])c1
Reactant: CCN(CC)CC
Agent: NOS(=O)(=O)O
Solvent: ClCCl
Solvent: O
Product: Cc1cnc(SN)c([N+](=O)[O-])c1

Procedure:
A solution of 12 g of 2-mercapto-5-methyl-3- nitropyridine and 28.6 g of triethylamine in 180 cm3 of dichloromethane is treated dropwise with 12 g of hydroxylamine-O-sulfonic acid dissolved in the minimum amount of water. At the end of the reaction, the solvent is removed under partial vacuum and the residue is taken up in 20 cm3 of water. The precipitate obtained is collected on a filter, washed with water and dried. It is recrystallized from a dichloromethane/petroleum jelly mixture.
Reaction SMILES: [CH2:1]([N:8]([CH2:15][C:16]1[C:21](Cl)=[N:20][C:19]([N:23]([CH3:28])[CH:24]([CH3:27])[CH2:25][CH3:26])=[CH:18][N:17]=1)[CH2:9][C@@H:10]([OH:14])[CH2:11][O:12][CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].O>CN(C=O)C>[CH2:1]([N:8]1[CH2:15][C:16]2[N:17]=[CH:18][C:19]([N:23]([CH3:28])[CH:24]([CH3:27])[CH2:25][CH3:26])=[N:20][C:21]=2[O:14][C@@H:10]([CH2:11][O:12][CH3:13])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCC(C)N(C)c1cnc(CN(Cc2ccccc2)C[C@@H](O)COC)c(Cl)n1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCC(C)N(C)c1cnc2c(n1)O[C@@H](COC)CN(Cc1ccccc1)C2
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 85.6 %

Procedure:
To a solution of (2R)-1-[benzyl({3-chloro-5-[methyl(1-methylpropyl)amino]pyrazin-2-yl}methyl)amino]-3-methoxypropan-2-ol (385 mg) in DMF (10 mL) was added potassium tert-butoxide (126 mg), and the mixture was stirred at room temperature for 1.5 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (solvent gradient: 20-+50% ethyl acetate/hexane) to give the title compound (300 mg, 86%).
Reaction SMILES: [CH3:1][N:2]([CH3:18])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[C:8]([F:17])=[CH:9][C:10]([N+:14]([O-])=O)=[C:11]([NH2:13])[CH:12]=1.[H][H]>CO.[Pd]>[CH3:18][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[C:11]([NH2:13])[C:10]([NH2:14])=[CH:9][C:8]=1[F:17]
Reactant: [H][H]
Reactant: CN(C)CCCOc1cc(N)c([N+](=O)[O-])cc1F
Agent: [Pd]
Solvent: CO
Product: CN(C)CCCOc1cc(N)c(N)cc1F
Yield: 104.3 %

Procedure:
3.8 g of 5-(3-dimethylaminopropoxy)-4-fluoro-2-nitrophenylamine in solution in 100 mL of methanol are hydrogenated under 1 bar of hydrogen pressure in the presence of 400 mg of palladium-on-charcoal at 25° C. for 16 hours. The reaction crude is filtered through celite and the filtrate is concentrated under vacuum in a rotary evaporator. 3.5 g of 4-(3-dimethylaminopropoxy)-5-fluorobenzene-1,2-diamine are isolated in the form of a black oil. 1H NMR (400 MHz, DMSO-d6, δ in ppm): 1.75 (m, 2H); 2.13 (m, 6H); 2.32 (m, 2H); 3.84 (m, 2H); 4.3 (m, 4H); 6.32 (m, 2H).
Reaction SMILES: [C:1]([C:3]1[C:4]([CH3:24])=[N:5][C:6]2[N:7]([CH:17]=[C:18]([CH2:20][C:21](O)=[O:22])[N:19]=2)[C:8]=1[C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[Cl:16])#[N:2].[CH:25]1[CH:30]=[N:29][C:28]2N(O)N=N[C:27]=2C=1.C(Cl)CCl.N1CCCC1>CC#N>[Cl:16][C:10]1[CH:11]=[C:12]([Cl:15])[CH:13]=[CH:14][C:9]=1[C:8]1[N:7]2[CH:17]=[C:18]([CH2:20][C:21](=[O:22])[N:29]3[CH2:28][CH2:27][CH2:25][CH2:30]3)[N:19]=[C:6]2[N:5]=[C:4]([CH3:24])[C:3]=1[C:1]#[N:2]
Reactant: Cc1nc2nc(CC(=O)O)cn2c(-c2ccc(Cl)cc2Cl)c1C#N
Reactant: On1nnc2cccnc21
Solvent: C1CCNC1
Solvent: ClCCCl
Solvent: CC#N
Product: Cc1nc2nc(CC(=O)N3CCCC3)cn2c(-c2ccc(Cl)cc2Cl)c1C#N
Reaction time: 0.08 h
Yield: 55.5 %

Procedure:
To a solution of 2-(6-cyano-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-2-yl)acetic acid (72 mg, 0.2 mmol) in CH3CN (0.7 mL) were added HOAT (41 mg, 0.3 mmol) and EDC (77 mg, 0.4 mmol). After one min all of the solids had dissolved to produce a clear tan to brown solution. At 5 min, pyrrolidine (14.5 mg, 0.2 mmol) was added. At 20 min from the addition of pyrrolidine, the reaction was quenched with EtOAc (3 mL) and then washed with satd aq NaHCO3 (2×3 mL), satd aq NH4Cl (2×3 mL), and water (3 mL). The organic layer was dried with MgSO4, filtered, and concentrated to yield 5-(2,4-dichlorophenyl)-7-methyl-2-(2-oxo-2-(pyrrolidin-1-yl)ethyl)imidazo[1,2-a]pyrimidine-6-carbonitrile (46 mg, 56%) as a yellow-brown oil.
Reaction SMILES: [F:1][C:2]1[CH:28]=[C:27]([N+:29]([O-])=O)[CH:26]=[CH:25][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[C:11]#[C:12][CH2:13][N:14]1[CH2:18][C@@H:17]([N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[C@H:16]([OH:24])[CH2:15]1.CN(C=O)C.CCO>[Fe].O>[NH2:29][C:27]1[CH:26]=[CH:25][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[CH:7][C:6]=2[C:11]#[C:12][CH2:13][N:14]2[CH2:18][C@@H:17]([N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[C@H:16]([OH:24])[CH2:15]2)=[C:2]([F:1])[CH:28]=1
Reactant: O=[N+]([O-])c1ccc(Oc2ccncc2C#CCN2C[C@@H](O)[C@H](N3CCCC3)C2)c(F)c1
Agent: [Fe]
Solvent: CCO
Solvent: CN(C)C=O
Solvent: O
Product: Nc1ccc(Oc2ccncc2C#CCN2C[C@@H](O)[C@H](N3CCCC3)C2)c(F)c1
Temperature: 100 °C
Yield: 49.2 %

Procedure:
A mixture of (3R,4R)-1-(3-(4-(2-fluoro-4-nitrophenoxy)pyridin-3-yl)prop-2-ynyl)-4-(pyrrolidin-1-yl)pyrrolidin-3-ol (35 mg, 0.082 mmol), DMF (1 mL), EtOH (1 mL) and H2O (1 mL) was treated with Fe powder (67 mg, 1.2 mmol, 2.4 mmol) and heated at 100° C. for 45 min. The mixture was filtered through Celite®, made basic with NaHCO3 and concentrate in vacuo. The residue was partitioned between EtOAc and saturated aq. NaHCO3 solution. The EtOAc phase was dried (MgSO4) and concentrated in vacuo to give the crude aniline (16 mg, 50%) which was used directly in the next step without further purification. MS(ESI+): m/z 397.28 (M+H)+.
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:8][C:7]2[CH:9]=[C:10]3[O:15][CH2:14][O:13][C:11]3=[CH:12][C:6]=2[C:5]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)=[N:4][N:3]1[C:25](Cl)=[S:26].CN(C)C=O.C(N(CC)CC)C.[C:40]([NH:43][NH2:44])(=[O:42])[CH3:41]>CN(C)C1C=CN=CC=1.O>[CH3:1][C@@H:2]1[CH2:8][C:7]2[CH:9]=[C:10]3[O:15][CH2:14][O:13][C:11]3=[CH:12][C:6]=2[C:5]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)=[N:4][N:3]1[C:25]([NH:44][NH:43][C:40](=[O:42])[CH3:41])=[S:26]
Reactant: C[C@@H]1Cc2cc3c(cc2C(c2ccc([N+](=O)[O-])cc2)=NN1C(=S)Cl)OCO3
Reactant: CC(=O)NN
Agent: CN(C)c1ccncc1
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(=O)NNC(=S)N1N=C(c2ccc([N+](=O)[O-])cc2)c2cc3c(cc2C[C@H]1C)OCO3
Temperature: 50 °C
Reaction time: 5 h

Procedure:
To a solution of 4.04 g (10.0 mmol) of the starting material XII, 3 ml of dimethylformamide, 1.40 ml (10.0 mmol) of triethylamine and 0.06 g (0.5 mmol) of 4-dimethylaminopyridine 1.48 g (20.0 mmol) of acetic hydrazide was added. The reaction mixture was stirred at 50° C. for 5 h, then diluted with water, the precipitated crystals were filtered off and washed with water. The so obtained 4.5 g of (R)—N′-{8-methyl-5-(4-nitrophenyl)-8,9-dihydro-7H-1,3-dioxolo[4,5-h][2,3]benzodiazepine-7-carbothioyl}-acetic hydrazide according to its 1H-NMR spectrum was a mixture of rotation isomers. (The analyzed sample was purified by column chromatography using a mixture of n-hexane-ethyl acetate (1:1) as eluent and it was crystallized with 0.5 mol of ethyl acetate, Mp.: 118° C.).
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:18][CH2:19][CH3:20])[CH2:5][N:6]1[C:10]([NH2:11])=[CH:9][C:8]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[N:7]1)[CH3:2].Br[C:22]1[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=[C:24]([Cl:31])[C:23]=1[CH3:32]>>[Cl:31][C:24]1[C:23]([CH3:32])=[C:22]([NH:11][C:10]2[N:6]([CH2:5][CH:4]([O:18][CH2:19][CH3:20])[O:3][CH2:1][CH3:2])[N:7]=[C:8]([C:12]3[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=3)[CH:9]=2)[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=1
Reactant: CCOC(Cn1nc(-c2cccnc2)cc1N)OCC
Reactant: Cc1c(Cl)cc([N+](=O)[O-])cc1Br
Product: CCOC(Cn1nc(-c2cccnc2)cc1Nc1cc([N+](=O)[O-])cc(Cl)c1C)OCC

Procedure:
Analogously to Example 13A/Step 1, 1.0 g (3.62 mmol) of the compound of Example 4A and 1.0 g (3.98 mmol) of 1-bromo-3-chloro-2-methyl-5-nitrobenzene gave 670 mg (42% of theory) of the title compound. The starting material 1-bromo-3-chloro-2-methyl-5-nitrobenzene can be prepared from 2-chloro-1-methyl-4-nitrobenzene by a process described in U.S. Pat. No. 5,877,191 for the preparation of 3-bromo-5-fluoro-4-methyl-1-nitrobenzene.
Reaction SMILES: [C:1]1([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([Cl:16])[CH:14]=3)[NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:17]1[CH2:22][CH2:21][N:20]([CH2:23][CH2:24]Cl)[CH2:19][CH2:18]1>>[ClH:16].[O:17]1[CH2:22][CH2:21][N:20]([CH:23]([C:14]2[C:13]([Cl:16])=[CH:12][CH:11]=[C:10]3[C:15]=2[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[N:8][NH:9]3)[CH3:24])[CH2:19][CH2:18]1
Reactant: Clc1ccc2[nH]nc(-c3ccccc3)c2c1
Reactant: ClCCN1CCOCC1
Product: CC(c1c(Cl)ccc2[nH]nc(-c3ccccc3)c12)N1CCOCC1
Product: Cl

Procedure:
By the procedure similar to that described in Example 13, 3-phenyl-5-chloroindazole (4.57 g) and morpholinoethyl chloride (3.59 g) were treated to obtain 3.7 jg of 1-morpholinoethyl-3-phenyl-5-chloroindazole hydrochloride (m.p. 226°-229° C).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[CH3:9].C([Li])(C)(C)C.CCCCC.[B:20](OC(C)C)([O:25]C(C)C)[O:21]C(C)C.Cl>C1COCC1>[CH3:9][C:3]1[C:4]([CH3:8])=[CH:5][CH:6]=[CH:7][C:2]=1[B:20]([OH:25])[OH:21]
Reactant: Cc1cccc(Br)c1C
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: Cl
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Solvent: CCCCC
Product: Cc1cccc(B(O)O)c1C
Temperature: -78 °C
Yield: 185.2 %

Procedure:
To a solution of 3-bromo-o-xylene (500 mg, 2.7 mmol) in THF (15 mL) at −78° C. under N2 was slowly added 1.7 M tert-butyl lithium in pentane (1.77 mL, 3.0 mmol). This was stirred at −78° C. for 30 m. To the reaction mixture was added B(OiPr)3 (2.05 g, 11 mmol), and the reaction mixture was raised to 20° C. and stirred for 2 h. 3 N HCl (10 mL) was added to the reaction mixture and the acidic solution was stirred for 90 m. The reaction mixture was extracted using EtOAc (4×50 mL), and the organic solution was extracted using a 1 N solution of NaOH (100 mL). The aqueous solution was washed with Et2O (2×50 mL), acidified to pH 1 using concentrated HCl, and then extracted using EtOAc (4×50 mL). The organic solution was then washed with brine (100 mL), dried over MgSO4 and concentrated in vacuo to afford 2,3-dimethylphenylboronic acid compound (750 mg, 45%) as a white solid.
Reaction SMILES: [C:1]12([CH2:11][CH2:12][NH:13][C:14]3[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][C:15]=3[F:21])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[C:22]([CH:25]=[C:26]=[O:27])(=[O:24])[CH3:23]>CCOC(C)=O>[C:1]12([CH2:11][CH2:12][NH:13][C:14]3[CH:19]=[CH:18][C:17]([NH:20][C:26](=[O:27])[CH2:25][C:22](=[O:24])[CH3:23])=[CH:16][C:15]=3[F:21])[CH2:2][CH:3]3[CH2:9][CH:7]([CH2:6][CH:5]([CH2:4]3)[CH2:10]1)[CH2:8]2
Reactant: Nc1ccc(NCCC23CC4CC(CC(C4)C2)C3)c(F)c1
Reactant: CC(=O)C=C=O
Solvent: CCOC(C)=O
Product: CC(=O)CC(=O)Nc1ccc(NCCC23CC4CC(CC(C4)C2)C3)c(F)c1
Temperature: 90 °C
Reaction time: 8 h
Yield: 64.5 %

Procedure:
To a solution of N1-(2-(adamantan-1-yl)ethyl)-2-fluorobenzene-1,4-diamine (0.38 g, 1.32 mmol) in EtOAc (20 mL) was added acetyl ketene (0.22 g, 2.62 mmol) and the mixture was stirred at 90° C. overnight. The mixture was then cooled to rt and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=4:1) to give the title compound as a white solid (317 mg, 64%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:15][C:14]3[C:16](O)=[C:17]4[O:23][CH2:22][O:21][C:18]4=[C:19]([OH:20])[C:13]=3[C:11](=[O:12])[CH:10]=2)=[CH:5][CH:4]=1.C1OC2C=C3C(C(=O)C=C(C4C=CC(O)=CC=4)O3)=C(O)C=2O1.COS(OC)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.C(OCC)(=O)C>[CH2:22]1[O:23][C:17]2[CH:16]=[C:14]3[C:13]([C:11](=[O:12])[CH:10]=[C:9]([C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=4)[O:15]3)=[C:19]([OH:20])[C:18]=2[O:21]1
Reactant: COc1ccc(-c2cc(=O)c3c(O)c4c(c(O)c3o2)OCO4)cc1
Agent: O=C([O-])[O-]
Agent: O=c1cc(-c2ccc(O)cc2)oc2cc3c(c(O)c12)OCO3
Agent: [K+]
Solvent: COS(=O)(=O)OC
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: COc1ccc(-c2cc(=O)c3c(O)c4c(cc3o2)OCO4)cc1

Procedure:
A solution of Kanzakiflavone-1 or 6,7-methylenedioxy-5,4′-dihydroxyflavone (1.49 g, 5 mmol) [Manchanda, V. P.; Khanna, R. N. Curr. Sci. (1977), 46(13), 445-6.] and dimethylsulfate (1.02 g, 8 mmol) in acetone (20 ml) is refluxed in the presence of anyhyd. potassium carbonate (0.5 g) overnight. The reaction mixture is filtered off and the filtrate is evaporated to give a dark brown residue. The residue is taken up in ethyl acetate and washed with water followed by saturated brine solution and dried (MgSO4), thus giving the title compound, upon filtration and evaporation.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:14](=[O:15])[NH:13][C:8]2=[N:9][CH:10]=[CH:11][N:12]=[C:7]2[C:6]=1[OH:16])=[O:4].[C:17](Cl)(=[O:21])[CH:18]([CH3:20])[CH3:19]>ClCCCl>[CH3:1][O:2][C:3]([C:5]1[C:14](=[O:15])[NH:13][C:8]2=[N:9][CH:10]=[CH:11][N:12]=[C:7]2[C:6]=1[O:16][C:17](=[O:21])[CH:18]([CH3:20])[CH3:19])=[O:4]
Reactant: COC(=O)c1c(O)c2nccnc2[nH]c1=O
Reactant: CC(C)C(=O)Cl
Solvent: ClCCCl
Product: COC(=O)c1c(OC(=O)C(C)C)c2nccnc2[nH]c1=O
Temperature: 25 °C

Procedure:
To a suspension of 8-hydroxy-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazine-7-carboxylic acid methyl ester (Example 7.1) in 1,2-dichloro-ethane (9 ml) was added powdered molecular sieves (4A) followed by dropwise addition of isobutyryl chloride (0.048 ml). The reaction mixture was heated to reflux for 5 hours, cooled to ambient temperature and filtered. The filtrate was concentrated to give 8-isobutyryloxy-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazine-7-carboxylic acid methyl ester as a light brown solid (0.166 g) which was used without further purification.
Reaction SMILES: [C:1]([O:4][C:5]1[C:6]([CH3:19])=[C:7]2[C:12](=[C:13]([CH3:16])[C:14]=1[CH3:15])[O:11][C:10]([OH:18])([CH3:17])[CH2:9][CH2:8]2)(=[O:3])[CH3:2].CS(C)=O.[C-:24]#[N:25].[K+]>C(OCC)C>[C:24]([C:10]([OH:18])([CH2:9][CH2:8][C:7]1[C:6]([CH3:19])=[C:5]([O:4][C:1](=[O:3])[CH3:2])[C:14]([CH3:15])=[C:13]([CH3:16])[C:12]=1[OH:11])[CH3:17])#[N:25]
Reactant: [C-]#N
Reactant: CC(=O)Oc1c(C)c(C)c2c(c1C)CCC(C)(O)O2
Agent: [K+]
Solvent: CCOCC
Solvent: CS(C)=O
Product: CC(=O)Oc1c(C)c(C)c(O)c(CCC(C)(O)C#N)c1C

Procedure:
A solution of 26.4 g. (0.1 mol.) of (±)-6-acetoxy-2-hydroxy-2,5,7,8 -tetramethylchroman in 200 ml. of dimethylsulfoxide was rapidly stirred as 32.5 g. (0.5 mol.) of granular KCN was added by sifting so that a uniformly dispersed suspension was obtained. The resulting mixture was cooled to 15° centigrade as 47.0 ml. of 12N aqueous H 2 SO 4 was added over 1.25 hours as the internal temp. was maintained at 20° centigrade. Tlc at this point showed a major, slower-running spot in addition to traces of starting material. The material was poured into diethylether and H 2 O. The ether solutions were washed with water and brine, dried over NaSO4 and stripped of solvent to yield (±)-2-cyano-4-(5-acetoxy-2-hydroxy-3,4,6-trimethylphenyl) butan-2-ol as a gum.