Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:6]([CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[C:7]([CH:9]([CH2:16][S:17]([C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=1)=[O:18])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[O:8])[CH2:2][CH2:3][CH2:4][CH3:5].ClC1C=CC=C(C(OO)=[O:39])C=1.S([O-])([O-])=O.[Na+].[Na+]>ClCCl>[CH2:26]([N:6]([CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])[C:7]([CH:9]([CH2:16][S:17]([C:19]1[CH:20]=[CH:21][C:22]([CH3:25])=[CH:23][CH:24]=1)(=[O:39])=[O:18])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[O:8])[CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: CCCCCN(CCCCC)C(=O)C(CCC(=O)OC)CS(=O)c1ccc(C)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: CCCCCN(CCCCC)C(=O)C(CCC(=O)OC)CS(=O)(=O)c1ccc(C)cc1
Temperature: 0 °C
Yield: 83.6 %

Procedure:
Into a solution of methyl 4-(N,N-dipentylcarbamoyl)-5-(4-methylphenylsulfinyl)pentanoate (0.15 g) in dry dichloromethane (5 ml) were added portions of m-chloroperbenzoic acid (80%, 0.09 g) with stirring at 0° C. After stirring at room temperature for 4 hours, sodium sulfite was added. The reaction mixture was washed with a saturated sodium bicarbonate solution and water, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica by eluting with dichloromethane/diethyl ether (2:1) to give 0.13 g of methyl 4-(N,N-dipentylcarbamoyl)-5-(4-methylphenylsulfonyl)pentanoate as an oil.
Reaction SMILES: C[O:2][C:3](=[O:24])[CH:4]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][C:10]=1[N+:21]([O-:23])=[O:22])C(OC)=O>Cl>[N+:21]([C:10]1[CH:11]=[C:12]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:13]=[CH:14][C:9]=1[CH2:4][C:3]([OH:24])=[O:2])([O-:23])=[O:22]
Reactant: COC(=O)C(C(=O)OC)c1ccc(-c2ccccc2)cc1[N+](=O)[O-]
Agent: Cl
Product: O=C(O)Cc1ccc(-c2ccccc2)cc1[N+](=O)[O-]

Procedure:
Crude dimethyl-3-nitrobiphenyl-4-malonate was refluxed in 30 mL of 6 N hydrochloric acid for 24 hours. The precipitate was collected by filtration, washed with water and dried to give 4.5 g of 3-nitrobiphenyl-4-acetic acid as a cream colored solid.
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)=[C:5]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:4]=[C:3]1[C:19]1[CH:27]=[CH:26][C:22]([C:23]([OH:25])=[O:24])=[CH:21][CH:20]=1.[Na].[CH2:29](N(CC)CC)C.S(Cl)(Cl)=O>C(Cl)Cl.CO>[CH3:29][O:24][C:23](=[O:25])[C:22]1[CH:21]=[CH:20][C:19]([C:3]2[N:2]([CH3:1])[C:6]([C:7]3[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=3)=[C:5]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:4]=2)=[CH:27][CH:26]=1
Reactant: CCN(CC)CC
Reactant: Cn1c(-c2ccc(C(=O)O)cc2)nc(-c2ccccc2)c1-c1ccncc1
Agent: [Na]
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Solvent: CO
Product: COC(=O)c1ccc(-c2nc(-c3ccccc3)c(-c3ccncc3)n2C)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 8 %

Procedure:
To a suspension of 4-[1-methyl-4-phenyl-5(4-pyridyl)-imidazol-2-yl]benzoic acid, sodium salt (20 mg, 0.06 mmol) [See Ex. 5 above] in CH2Cl2 (2 mL) was added triethylamine (24 mL, 0.17 mmol), followed by thionyl chloride (10 mL, 0.14 mmol). The reaction mixture was stirred at rt for 30 min, at which time MeOH (0.5 mL) was added. The mixture was stirred at rt for an additional 2 h and concentrated under reduced pressure. The residue was purified by flash chromatography, eluting with a solvent gra-dient of 0-1% MeOH/CHCl3 and recrystallized from EtOAc to afford the title compound as an off-white crystalline solid (1.6 mg, 8%): mp 208-209° C.
Reaction SMILES: [CH2:1]([N:8]([CH2:13][CH:14]([CH2:25][O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[CH:15]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=1)[OH:16])[C:9](=[O:12])[CH2:10]Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+]>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH:14]([CH2:25][O:26][Si:27]([C:30]([CH3:32])([CH3:33])[CH3:31])([CH3:29])[CH3:28])[CH:15]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)[O:16][CH2:10][C:9]1=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)[Si](C)(C)OCC(CN(Cc1ccccc1)C(=O)CCl)C(O)c1ccc(Cl)c(Cl)c1
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OCC1CN(Cc2ccccc2)C(=O)COC1c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.1 %

Procedure:
To a solution of N-benzyl-N-[(2RS,3RS)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-(3,4-dichlorophenyl)-3-hydroxypropyl]-2-chloroacetamide (2.72 g) in THF (100 ml) was added sodium tert-butoxide (621 mg) under ice-cooling, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate. The diluted solution was washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound (2.51 g).
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([C:10]1[N:11]([CH2:24][CH2:25][O:26][CH2:27][CH2:28][NH:29]C(=O)OC(C)(C)C)[C:12]2[C:17]([CH3:18])=[C:16]([CH3:19])[N:15]3[N:20]=[N:21][N:22]=[C:14]3[C:13]=2[N:23]=1)[CH3:9]>ClCCl>[CH2:8]([C:10]1[N:11]([CH2:24][CH2:25][O:26][CH2:27][CH2:28][NH2:29])[C:12]2[C:17]([CH3:18])=[C:16]([CH3:19])[N:15]3[N:20]=[N:21][N:22]=[C:14]3[C:13]=2[N:23]=1)[CH3:9]
Reactant: CCc1nc2c(c(C)c(C)n3nnnc23)n1CCOCCNC(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCc1nc2c(c(C)c(C)n3nnnc23)n1CCOCCN
Reaction time: 8 h
Yield: 77.7 %

Procedure:
A solution of trifluoroacetic acid (188 mL, 2.44 mol) in dichloromethane (300 mL) was cooled to 0° C. A solution of tert-butyl 2-{2-[(8-ethyl-5,6-dimethyl-7H-imidazo[4,5-c]tetrazolo[1,5-a]pyridin-7-yl)]ethoxy}ethylcarbamate (19.7 g, 48.8 mmol) in dichloromethane (300 mL) was then slowly added over a period of 30 minutes, and the reaction was stirred overnight. The volatiles were removed under reduced pressure, and the residual brown oil was stirred with 2-propanol (300 mL) to form a white salt, which was isolated by filtration and dried in a vacuum at 80° C. The salt was dissolved in water (200 mL), and solid sodium carbonate was added to adjust to pH 12. The solution was extracted with chloroform overnight with a continuous extractor. The extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 11.5 g of 2-[2-(8-ethyl-5,6-dimethyl-7H-imidazo[4,5-c]tetrazolo[1,5-a]pyridin-7-yl)ethoxy]ethylamine as a white solid, m. p. 181–183° C.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([Br:24])(Br)(Br)[Br:21].[C:25]([C:28]1[C:29]([C:45]#[N:46])=[N:30][N:31]([C:33]2[C:38]([Cl:39])=[CH:37][C:36]([C:40]([F:43])([F:42])[F:41])=[CH:35][C:34]=2[Cl:44])[CH:32]=1)(=O)[CH3:26]>ClCCl>[C:45]([C:29]1[C:28]([C:25]([CH3:26])=[C:20]([Br:24])[Br:21])=[CH:32][N:31]([C:33]2[C:38]([Cl:39])=[CH:37][C:36]([C:40]([F:43])([F:41])[F:42])=[CH:35][C:34]=2[Cl:44])[N:30]=1)#[N:46]
Reactant: CC(=O)c1cn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)nc1C#N
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CC(=C(Br)Br)c1cn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)nc1C#N

Procedure:
A solution of triphenylphosphine (0.94 g) and carbon tetrabromide (0.6 g) in anhydrous dichloromethane (30 ml) at 0° C. was stirred for 5 minutes. 4-Acetyl-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole (0.25 g) was then added and the mixture was heated under reflux for 6 hours and then evaporated. The residue was purified by column chromatography on silica gel eluted with dichloromethane. Combination and evaporation of suitable fractions gave the title compound as a pale pink solid, m.p. 119-122° C.
Reaction SMILES: C([C:8]1[C:13]([CH:14]=[C:15]([C:17](=[O:31])[NH:18][CH:19]2[CH:27]([OH:28])[CH:26]([OH:29])[CH:22]3[O:23][CH2:24][O:25][CH:21]3[CH:20]2[OH:30])[CH3:16])=[CH:12][C:11]([O:32][P:33](=[O:36])([OH:35])[OH:34])=[C:10]([O:37][CH:38]2[CH:42]([OH:43])[CH:41]([OH:44])[CH:40](/[C:45](=[N:47]/[O:48][CH2:49][C:50]3[CH:55]=[CH:54][CH:53]=[C:52]([Cl:56])[CH:51]=3)/[CH3:46])[O:39]2)[C:9]=1CC1C=CC=CC=1)C1C=CC=CC=1.C1CC=CCC=1>[Pd]>[Cl:56][C:52]1[CH:51]=[C:50]([CH:55]=[CH:54][CH:53]=1)[CH2:49][O:48]/[N:47]=[C:45](/[CH:40]1[O:39][CH:38]([O:37][C:10]2[CH:9]=[CH:8][C:13]([CH:14]=[C:15]([C:17](=[O:31])[NH:18][CH:19]3[CH:27]([OH:28])[CH:26]([OH:29])[CH:22]4[O:23][CH2:24][O:25][CH:21]4[CH:20]3[OH:30])[CH3:16])=[CH:12][C:11]=2[O:32][P:33](=[O:34])([OH:36])[OH:35])[CH:42]([OH:43])[CH:41]1[OH:44])\[CH3:46]
Reactant: CC(=Cc1cc(OP(=O)(O)O)c(OC2OC(/C(C)=N/OCc3cccc(Cl)c3)C(O)C2O)c(Cc2ccccc2)c1Cc1ccccc1)C(=O)NC1C(O)C(O)C2OCOC2C1O
Agent: [Pd]
Solvent: C1=CCC=CC1
Product: CC(=Cc1ccc(OC2OC(/C(C)=N/OCc3cccc(Cl)c3)C(O)C2O)c(OP(=O)(O)O)c1)C(=O)NC1C(O)C(O)C2OCOC2C1O
Yield: 82.1 %

Procedure:
A solution of phosphoric acid dibenzyl-(2-(5-(1-(3-chloro-benzyloxy-E-imino)-ethyl)-3,4-dihydroxy-tetrahydro-furan-2-yloxy)-5-(2-(4,6,7-trihydroxy-hexahydro-benzo(1,3)dioxol-5-ylcarbamoyl)-propenyl)-phenyl) ester (95 mg, 0.105 mmol) and 168 mg of 1,4-cyclohexadiene (2.1 mmol) and 95 mg 10% palladium on carbon was stirred under nitrogen for 20 hours. The reaction mixture was filtered through Celite and evaporated. The residue was chromatographed on reversed phase SiO2 (30% methanol/water) to give 63 mg of the title compound; MS m/e 731 (M+).
Reaction SMILES: Cl[C:2]([C:4]1[C:5]2[CH2:25][CH2:24][CH2:23][CH2:22][C:6]=2[S:7][C:8]=1[NH:9][C:10]([C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:13]=1)=[O:11])=[O:3].[O:26]1[C:30]2[CH:31]=[CH:32][C:33]([CH2:35][NH2:36])=[CH:34][C:29]=2[O:28][CH2:27]1.N1C=CC=CC=1>ClCCl>[O:26]1[C:30]2[CH:31]=[CH:32][C:33]([CH2:35][NH:36][C:2]([C:4]3[C:5]4[CH2:25][CH2:24][CH2:23][CH2:22][C:6]=4[S:7][C:8]=3[NH:9][C:10]([C:12]3[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:13]=3)=[O:11])=[O:3])=[CH:34][C:29]=2[O:28][CH2:27]1
Reactant: NCc1ccc2c(c1)OCO2
Reactant: COC(=O)c1ccc(C(=O)Nc2sc3c(c2C(=O)Cl)CCCC3)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)c1ccc(C(=O)Nc2sc3c(c2C(=O)NCc2ccc4c(c2)OCO4)CCCC3)cc1

Procedure:
Methyl 4-(3-chlorocarbonyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-ylcarbamoyl)benzoate is added to a solution of (benzo[1,3]dioxol-5-ylmethyl)amine in dichloromethane and 1.1 equivalents of pyridine and the solution is stirred. The solvent is removed and is worked up in a customary manner. 1.3 g of methyl 4-{3[(benzo[1,3]dioxol-5-ylmethyl)carbamoyl]-4,5,6,7-tetrahydrobenzo[b]thiophene-2-ylcarbamoyl}benzoate, m.p. 165°, are obtained.
Reaction SMILES: [Cl:1][C:2]1[C:7](OC2C=CC=CC=2)=[C:6]([N+:15]([O-:17])=[O:16])[CH:5]=[CH:4][C:3]=1[O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[F:25][C:26]([F:36])([F:35])[C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[CH2:30][NH2:31]>O1CCOCC1>[Cl:1][C:2]1[C:3]([O:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:4][CH:5]=[C:6]([N+:15]([O-:17])=[O:16])[C:7]=1[NH:31][CH2:30][C:29]1[CH:32]=[CH:33][CH:34]=[C:27]([C:26]([F:25])([F:35])[F:36])[CH:28]=1
Reactant: NCc1cccc(C(F)(F)F)c1
Reactant: O=[N+]([O-])c1ccc(Oc2ccccc2)c(Cl)c1Oc1ccccc1
Solvent: C1COCCO1
Product: O=[N+]([O-])c1ccc(Oc2ccccc2)c(Cl)c1NCc1cccc(C(F)(F)F)c1
Temperature: 100 °C
Reaction time: 12 h

Procedure:
A mixture of 3.41 gm of 2-chloro-4-nitro-1,3-diphenoxy-benzene, 5 ml of dioxane and 4 gm of 3-trifluoromethyl-benzylamine was stirred for 12 hours at 100° C. Thereafter, the reaction mixture was evaporated, the residue was taken up in chloroform, the resulting solution was extracted first with 2 N sodium hydroxide and then with 2 N hydrochloric acid, and the organic phase was dried with sodium sulfate. The chloroform was distilled off, leaving 4.0 gm (95% of theory) of the title compound as a viscous yellow oil.
Reaction SMILES: COC(=O)CC1C=CC(Cl)=CC=1Cl.C(OC1C=C(C=CN=1)C(O)=O)C1C=CC=CC=1.C([O:38][C:39]1[CH:44]=[C:43]([C:45]([OH:60])([CH:50]([C:52]2[CH:57]=[CH:56][C:55]([Cl:58])=[CH:54][C:53]=2[Cl:59])[CH3:51])[C:46]([F:49])([F:48])[F:47])[CH:42]=[CH:41][N:40]=1)C1C=CC=CC=1.CI>[Pd]>[Cl:59][C:53]1[CH:54]=[C:55]([Cl:58])[CH:56]=[CH:57][C:52]=1[CH:50]([CH3:51])[C:45]([C:43]1[CH:42]=[CH:41][NH:40][C:39](=[O:38])[CH:44]=1)([OH:60])[C:46]([F:49])([F:48])[F:47]
Reactant: CC(c1ccc(Cl)cc1Cl)C(O)(c1ccnc(OCc2ccccc2)c1)C(F)(F)F
Agent: [Pd]
Agent: COC(=O)Cc1ccc(Cl)cc1Cl
Agent: O=C(O)c1ccnc(OCc2ccccc2)c1
Solvent: CI
Product: CC(c1ccc(Cl)cc1Cl)C(O)(c1cc[nH]c(=O)c1)C(F)(F)F

Procedure:
The title compound was prepared in analogy to Example 1, steps 2 to 5, from 2,4-dichlorobenzeneacetic acid methyl ester [CAS Reg. No. 91361-41-0] and 2-benzyloxy-isonicotinic acid (which was made as described below from 2-chloro isonicotinic acid), leading to 2-(2-benzyloxy-pyridin-4-yl)-3-(2,4-dichloro-phenyl)-1,1,1-trifluoro-butan-2-ol, followed by cleavage of the benzyl protecting group by hydrogenation over Pd/C-10% (0.75 g) in ethyl actetate (150 ml). In step 4, methyl iodide was used as an alkylating agent and the improved procedure described in example 117 was used. MS (m/e)=364.0 [MH+].
Reaction SMILES: [OH:1]C1C=CC(C2C=CC(O)=CC=2)=CC=1.C(O)(=O)CCCC[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27]>>[OH:1][C:22]1[CH:21]=[CH:20][C:25]([C:26]([OH:28])=[O:27])=[CH:24][CH:23]=1
Reactant: Oc1ccc(-c2ccc(O)cc2)cc1
Reactant: O=C(O)CCCCCCCCCCC(=O)O
Product: O=C(O)c1ccc(O)cc1

Procedure:
Polymerization was carried out in the same way as Example 1, except that (A) preparing materials were changed to 4,4′-dihydroxybiphenyl, dodecanedioic acid, 4-hydroxybenzoic acid, acetic anhydride, and (B) a mixture of 4,4′-dihydroxybiphenyl, dodecanedioic acid, 4-hydroxybenzoic acid, acetic anhydride at a molar ratio of 1.05:1:2:4.1 in which 4,4′-dihydroxybiphenyl was excess by 5 mol % was prepared in a reactor vessel, thereby producing a thermoplastic resin in which 4-hydroxybenzoic acid was copolymerized with the resin of Example 1. A molecular structure, sealed end groups, and a sealing rate of ends are shown in Table 2, and changes in number average molecular mass and thermal conductivity before and after melting are shown in Table 3.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C:14]2[CH:19]=[C:18](Cl)[N:17]=[N:16][C:15]=2[NH:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[O:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]>CO.[Pd]>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([NH:11][C:12]([C:14]2[CH:19]=[CH:18][N:17]=[N:16][C:15]=2[NH:21][CH2:22][C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)=[O:13])=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc(NC(=O)c2cc(Cl)nnc2NCc2ccc(F)cc2)cc1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)c1ccc(NC(=O)c2ccnnc2NCc2ccc(F)cc2)cc1
Temperature: 25 °C
Reaction time: 26 h

Procedure:
A mixture of 6-chloro-3-(4-fluoro-benzylamino)-pyridazine-4-carboxylic acid (4-tert-butyl-phenyl)-amide (0.210 g, 0.51 mmol) and Pd/C (50 mg, 10% weight) in 10 mL of MeOH was placed under H2 from a balloon and stirred at RT for 26 h, filtered through Celite®, condensed, and purified by flash column chromatography (0.5% to 2% of MeOH in CH2Cl2, then 1% of MeOH and 1% of NH4OH in CH2Cl2). The titled product was obtained as a light yellowish solid. MS (ES+): 379.0(M+H)+. Calc'd for C22H23FN4O-378.44.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([Cl:9])=[CH:4][C:3]=1[C:10]1[NH:14][NH:13][C:12](=[O:15])[C:11]=1[C:16]([O:18]CC)=O.C(O)C>CN(C)C=O>[Cl:8][C:6]1[C:5]([Cl:9])=[CH:4][C:3]2[C:10]3[NH:14][NH:13][C:12](=[O:15])[C:11]=3[C:16]([OH:18])=[N:1][C:2]=2[CH:7]=1
Reactant: CCOC(=O)c1c(-c2cc(Cl)c(Cl)cc2N)[nH][nH]c1=O
Solvent: CCO
Solvent: CN(C)C=O
Product: O=c1[nH][nH]c2c1c(O)nc1cc(Cl)c(Cl)cc12

Procedure:
0.63 g (0.002 mol) of ethyl 5-(2-amino-4,5-dichlorophenyl)-3-oxo-2,3-dihydro-1H-pyrazole-4-carboxylate was dissolved in 10 ml of dimethylformamide and boiled under reflux for 1/2 hr. The mixture was cooled, the suspension was treated with 50 ml of ethanol, suction filtered and dried in a vacuum. Yield: 0.18 g (33%) of 7,8-dichloro-4-hydroxy-2,3-dihydro-1H-pyrazolo[4,3-c]quinolin-3-one as beige crystals; m.p. >350° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]1[NH:16][C:15](=[O:17])[CH2:14][CH2:13][CH2:12]1.Br[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1>>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][N:16]2[CH:11]([C:4]3[C:5]([O:9][CH3:10])=[CH:6][CH:7]=[CH:8][C:3]=3[O:2][CH3:1])[CH2:12][CH2:13][CH2:14][C:15]2=[O:17])=[CH:21][CH:22]=1
Reactant: Clc1ccc(CBr)cc1
Reactant: COc1cccc(OC)c1C1CCCC(=O)N1
Product: COc1cccc(OC)c1C1CCCC(=O)N1Cc1ccc(Cl)cc1

Procedure:
Prepared according to the described general procedure 4 (GP4) by reaction of 6-(2,6-dimethoxyphenyl)piperidin-2-one with commercially available 1-(bromomethyl)-4-chlorobenzene. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions E): tR=0.77 min.; [M+H]+: 360.18 g/mol.
Reaction SMILES: [F:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:17]=[CH:16][NH:15][N:14]=3)=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:23]1[N:28]=[CH:27][CH:26]=[CH:25][N:24]=1>C1COCC1>[F:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]([C:13]3[CH:17]=[CH:16][N:15]([C:23]4[N:28]=[CH:27][CH:26]=[CH:25][N:24]=4)[N:14]=3)=[CH:11][CH:12]=2)=[CH:4][CH:3]=1
Reactant: Clc1ncccn1
Reactant: Fc1ccc(Oc2ccc(-c3cc[nH]n3)cc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Fc1ccc(Oc2ccc(-c3ccn(-c4ncccn4)n3)cc2)cc1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 81.7 %

Procedure:
To a solution of 3-[4-(4-fluorophenoxy)phenyl]-1H-pyrazole (930 mg, 3.66 mmol) in 15 mL of dry THF was slowly added 240 mg (6.00 mmol) of NaH. After stirring at room temperature for 20 minutes, 500 mg (4.15 mmol) of 2-chloropyrimidine was added in one portion. The reaction was allowed to stir overnight at room temperature and concentrated to dryness. The residue was dissolved in CHCl3 and subjected to flash chromatography. Elution with 3:2 hexane/EtOAc gave 994 mg of the title compound as a solid, mp 123-125° C. 1H NMR (CDCl3): δ8.77 (d, 2H, J=4.8 Hz), 8.65 (d, 1H, J=3.0 Hz), 7.95 (d, 2H, J=8.7 Hz), 7.20 (t, 1H, J=4.9 Hz), 7.07-6.98 (m, 5H), 6.78 (d, 1H, J=3.0 Hz).
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[NH2:15][C:16]1[C:21]([N+:22]([O-:24])=[O:23])=[CH:20][CH:19]=[C:18](Cl)[N:17]=1.C(N(C(C)C)CC)(C)C>CS(C)=O>[NH2:15][C:16]1[N:17]=[C:18]([NH:1][CH:2]2[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]2)[CH:19]=[CH:20][C:21]=1[N+:22]([O-:24])=[O:23]
Reactant: Nc1nc(Cl)ccc1[N+](=O)[O-]
Reactant: CC(C)(C)OC(=O)N1CCCC(N)C1
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CCCC(Nc2ccc([N+](=O)[O-])c(N)n2)C1
Temperature: 120 °C

Procedure:
500 mg (2.11 mmol) of tert-butyl 3-aminopiperidine-1-carboxylate, 772 mg (4.22 mmol) of 2-amino-6-chloro-3-nitropyridine and 1.05 ml (6.34 mmol) of diisopropylethylamine were suspended in 18 ml of DMSO and heated in a microwave reactor at 120° C. for 45 min. The reaction mixture was purified by preparative RP-HPLC (Method 11). This gave 600 mg (81% of theory) of the product as a solid.
Reaction SMILES: [Br:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([OH:9])=O)[N:6]=1.C[N:11](C=O)C.S(Cl)(Cl)=O.[OH-].[NH4+]>C(Cl)Cl.C(OCC)(=O)C>[Br:1][C:2]1[S:3][CH:4]=[C:5]([C:7]([NH2:11])=[O:9])[N:6]=1
Reactant: CN(C)C=O
Reactant: O=C(O)c1csc(Br)n1
Agent: [NH4+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Product: NC(=O)c1csc(Br)n1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a suspension of 2-bromo-1,3-thiazole-4-carboxylic acid (3.82 g, 18.4 mmol) and a catalytic amount of DMF in CH2Cl2 (100 mL) at 0° C. was slowly added thionyl chloride (14 mL of a 2M solution in CH2Cl2). The resulting mixture was stirred for 12 h at the room temperature and then heated to reflux for 1 h. The mixture was concentrated to dryness in vacuo. The white solid obtained was taken up in ethyl acetate, added to a pre-cooled (0° C.) 9-10% aqueous ammonium hydroxide solution (90 ml) and stirred for 1 h at 0° C. The organic layer was separated and the aqueous phase was extracted twice with ethyl acetate. The combined ethyl acetate solution was washed with brine, dried over magnesium sulfate and concentrated in vacuo, affording the title compound was obtained as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.60 (s, 1H), 7.82 (s, 1H), 8.22 (s, 1H).
Reaction SMILES: CS(O[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]2[N:24]=[CH:23][C:22]3[CH2:21][CH:20]([C:25]4[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=4)[C:19]4[CH:33]=[CH:34][CH:35]=[CH:36][C:18]=4[C:17]=3[N:16]=2)=[CH:10][CH:9]=1)(=O)=O.[NH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1>>[Cl:32][C:27]1[CH:26]=[C:25]([CH:20]2[C:19]3[CH:33]=[CH:34][CH:35]=[CH:36][C:18]=3[C:17]3[N:16]=[C:15]([NH:14][C:11]4[CH:10]=[CH:9][C:8]([CH2:7][CH2:6][N:37]5[CH2:42][CH2:41][O:40][CH2:39][CH2:38]5)=[CH:13][CH:12]=4)[N:24]=[CH:23][C:22]=3[CH2:21]2)[CH:30]=[CH:29][C:28]=1[Cl:31]
Reactant: C1COCCN1
Reactant: CS(=O)(=O)OCCc1ccc(Nc2ncc3c(n2)-c2ccccc2C(c2ccc(Cl)c(Cl)c2)C3)cc1
Product: Clc1ccc(C2Cc3cnc(Nc4ccc(CCN5CCOCC5)cc4)nc3-c3ccccc32)cc1Cl
Yield: 55 %

Procedure:
This product was synthesized as described in general procedure 2 except 4-(6-(3,4-dichlorophenyl)-5,6-dihydrobenzo[h]quinazolin-2-ylamino)phenethyl methanesulfonate was used instead of 4-(6-(3-bromophenyl)-5,6-dihydrobenzo[h]quinazolin-2-ylamino)phenethyl methanesulfonate and morpholine was used instead of piperidine to afford 6-(3,4-dichlorophenyl)-N-(4-(2-morpholinoethyl)phenyl)-5,6-dihydrobenzo[h]quinazolin-2-amine in 55% yield. M.p.=180-181° C. 1H NMR 400 MHz (CDCl3) δ 8.45-8.4 (m, 1H), 8.17 (s, 1H), 7.62 (d, J=8.4 Hz, 2H), 7.58-6.85 (m, 6H), 4.18-4.0 (m, 1H), 3.84-3.68 (m, 4H), 3.35-3.18 (m, 1H), 3.18-3.0 (m, 1H), 2.92-2.73 (m, 2H), 2.7-2.45 (m, 6H). LCMS m/e 532 (M+H).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][C:13](=O)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:17][N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.CC(O)=O.[BH3-]C#N.[Na+]>CO>[CH3:17][N:18]1[CH2:23][CH2:22][N:21]([CH:13]2[CH2:14][CH2:15][N:10]([C:7]3[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3)[CH2:11][CH2:12]2)[CH2:20][CH2:19]1
Reactant: O=C1CCN(c2ccc([N+](=O)[O-])cc2)CC1
Reactant: CN1CCNCC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CN1CCN(C2CCN(c3ccc([N+](=O)[O-])cc3)CC2)CC1
Temperature: 25 °C
Reaction time: 5 h
Yield: 39.8 %

Procedure:
A mixture of 1-(4-Nitro-phenyl)-piperidin-4-one (84 mg, 0.38 mmol) and 1-methylpiperazine (0.085 mL, 0.76 mmol) in MeOH (2 mL) is stirred at room temperature for 5 hours. Then to the reaction mixture is added 0.2 mL of HOAc, followed by NaCNBH3 (72 mg, 1.14 mmol). The mixture is stirred at room temperature for 0.5 hour, then concentrated. The residue is taken up in EtOAc, washed with saturated NaHCO3 aqueous solution and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product is purified by column chromatography (SiO2, 2N NH3 in MeOH:CH2Cl2=1:99 to 10:90) to give 46 mg of the title compound as a yellow solid.