Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH3:20])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:21](OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:22][CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:39]([C:42]1[CH:47]=[CH:46][C:45](B(O)O)=[CH:44][CH:43]=1)(=[O:41])[CH3:40].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH3:20])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:21]([C:45]2[CH:46]=[CH:47][C:42]([C:39](=[O:41])[CH3:40])=[CH:43][CH:44]=2)=[CH:22][CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)(=[O:8])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COc1cnc2c(c1)cc(C(=CC1CCCC1)OS(=O)(=O)c1ccc(C)cc1)n2S(=O)(=O)c1ccccc1
Reactant: CC(=O)c1ccc(B(O)O)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: COc1cnc2c(c1)cc(C(=CC1CCCC1)c1ccc(C(C)=O)cc1)n2S(=O)(=O)c1ccccc1
Yield: 93.8 %

Procedure:
To a mixture of toluene-4-sulfonic acid-1-(benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-vinyl ester (prepared as in Example 12, 1 g, 1.81 mmol), 4-acetylphenylboronic acid (743 mg, 4.53 mmol), and dichlorobis(triphenylphosphine)palladium (II) (127 mg, 0.18 mmol) in dioxane (5 mL) was added an aqueous sodium carbonate solution (2 M, 2.3 mL, 4.6 mmol). The resulting mixture was subjected to microwave irradiation for 2 h at 100° C. The mixture was diluted with ethyl acetate (250 mL), washed with a saturated aqueous sodium bicarbonate solution (2×50 mL), brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 20% ethyl acetate/hexanes) afforded 1-{4-[1-(1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-vinyl]-phenyl}-ethanone (850 mg, 93.9%) as a light yellow solid: LC/MS m/e calcd for C29H28N2O4S [M+H]+ 501.62, observed 501.2.
Reaction SMILES: [Cl:1]/[CH:2]=[C:3]1/[C@:4]2([CH2:20][CH2:19][C@H:18]3[C@@H:9]([CH2:10][CH2:11][C:12]4[C@@H:17]3[CH2:16][CH2:15][C:14](=[O:21])[CH:13]=4)[C@@H:6]2[CH2:7][CH2:8]/1)[CH3:5].[OH:22]O.[OH-].[Na+]>CO.C(Cl)Cl>[Cl:1]/[CH:2]=[C:3]1/[C@:4]2([CH2:20][CH2:19][C@H:18]3[C@@H:9]([CH2:10][CH2:11][C:12]45[O:22][CH:13]4[C:14](=[O:21])[CH2:15][CH2:16][C@@H:17]53)[C@@H:6]2[CH2:7][CH2:8]/1)[CH3:5]
Reactant: OO
Reactant: C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@H]43)[C@@H]1CC/C2=C\Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CO
Product: C[C@]12CC[C@H]3[C@@H](CCC45OC4C(=O)CC[C@H]35)[C@@H]1CC/C2=C\Cl
Temperature: 0 °C

Procedure:
3.93 mmol (1.2 9) of E-17-chloromethylen-estr-4-en-3-one is dissolved in a mixture of 12 ml of methanol and 10 ml of methylene chloride under a cover gas (argon) and cooled to 0° C. 9.2 mmol (0.94 ml) of hydrogen peroxide (30%) and 1.65 mmol (0.4 ml) of sodium hydroxide solution (c=4 mol/l) are added in drops in succession to the cooled solution while being stirred. After dropwise addition is completed, the temperature is slowly increased to room temperature. After about 1.5 hours of reaction time, the mixture is added to ice water and extracted with methylene chloride. The combined extracts are dried on sodium sulfate and concentrated by evaporation. 1.1 g of a white, sticky foam is obtained.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[NH:15][C:14](=[O:16])[O:13][C:12]([CH3:18])([CH3:17])[C:11]=2[CH:19]=1.[C:20]([C:24]1[CH:25]=[C:26]([SH:35])[CH:27]=[C:28]([C:31]([CH3:34])([CH3:33])[CH3:32])[C:29]=1[OH:30])([CH3:23])([CH3:22])[CH3:21]>>[C:20]([C:24]1[CH:25]=[C:26]([S:35][CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[CH:8]=[CH:9][C:10]3[NH:15][C:14](=[O:16])[O:13][C:12]([CH3:18])([CH3:17])[C:11]=3[CH:19]=2)[CH:27]=[C:28]([C:31]([CH3:34])([CH3:33])[CH3:32])[C:29]=1[OH:30])([CH3:23])([CH3:22])[CH3:21]
Reactant: CC1(C)OC(=O)Nc2ccc(OCCCCCl)cc21
Reactant: CC(C)(C)c1cc(S)cc(C(C)(C)C)c1O
Product: CC(C)(C)c1cc(SCCCCOc2ccc3c(c2)C(C)(C)OC(=O)N3)cc(C(C)(C)C)c1O

Procedure:
Prepared analogously to Example 1 from 6-(4-chlorobutoxy)-4,4-dimethyl-4H-3,1-benzoxazin-2-one and 3,5-di-tert.butyl-4-hydroxy-thiophenol.
Reaction SMILES: [H-].[Na+].Cl.[NH2:4][C:5]([NH2:7])=[NH:6].Cl[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([S:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)(=[O:21])=[O:20])[CH:17]=2)[C:12]([Cl:28])=[CH:11][N:10]=1.O>CS(C)=O>[Cl:28][C:12]1[C:13]2[C:18](=[CH:17][C:16]([S:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)(=[O:20])=[O:21])=[CH:15][CH:14]=2)[C:9]([NH:6][C:5]([NH2:7])=[NH:4])=[N:10][CH:11]=1
Reactant: N=C(N)N
Reactant: O=S(=O)(c1ccccc1)c1ccc2c(Cl)cnc(Cl)c2c1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: N=C(N)Nc1ncc(Cl)c2ccc(S(=O)(=O)c3ccccc3)cc12
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 76.3 %

Procedure:
NaH (18 mg, 80% dispersion by wt in mineral oil, 0.60 mmol) was added in one portion to a solution of guanidine hydrochloride (90 mg, 0.94 mmol) in DMSO (2 mL) and the mixture was heated at 50° C. under N2 for 30 min. 1,4-Dichloro-7-(phenylsulfonyl)isoquinoline (80 mg, 0.236 mmol) was added and the mixture heated at 50-60 C. for 0.5 h. The cooled mixture was poured into water (30 mL) and extracted with EtOAc (3×20 mL). The combined organic extracts were washed with brine, dried (Na2SO4) and evaporated in vacuo. The residue was dissolved in EtOAc and a solution of HCl in Et2O (1 M) was added which gave a precipitate. The solvents were evaporated in vacuo and the residue triturated with EtOAc to give 4-chloro-1-guanidino-7-(phenylsulphonyl)isoquinoline (65 mg, 0.18 mmol) as a yellow solid.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:21][C:22]1[CH:27]=[C:26]([F:28])[C:25]([F:29])=[CH:24][C:23]=1[F:30])[CH2:10][C:11]([O:13]CC1C=CC=CC=1)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2]>[Pd].CO>[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:21][C:22]1[CH:27]=[C:26]([F:28])[C:25]([F:29])=[CH:24][C:23]=1[F:30])[CH2:10][C:11]([OH:13])=[O:12])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@@H](CC(=O)OCc1ccccc1)Cc1cc(F)c(F)cc1F
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)N[C@@H](CC(=O)O)Cc1cc(F)c(F)cc1F
Yield: 96.4 %

Procedure:
58 mg of (R)-benzyl 3-(t-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoate, 3 mL of methanol, and 20 mg of 10 wt % palladium/carbon were added to 25 mL flask and the resulting reaction solution was stirred. A hydrogen gas was bubbled for 2 hours at room temperature; the reaction solution was filtered by passing through celite, washed with 15 mL of ethyl acetate, and the filtrate was concentrated under reduced pressure to obtain 44 mg of a title compound.
Reaction SMILES: [CH3:1][C:2]1([CH2:7][CH2:8][CH2:9][CH2:10][N:11]2[CH:15]=[C:14]([NH2:16])[CH:13]=[N:12]2)[O:6]CCO1.[C:17]1([C:23]2[O:27][CH:26]=[N:25][C:24]=2[C:28](O)=[O:29])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[O:6]=[C:2]([CH3:1])[CH2:7][CH2:8][CH2:9][CH2:10][N:11]1[CH:15]=[C:14]([NH:16][C:28]([C:24]2[N:25]=[CH:26][O:27][C:23]=2[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[O:29])[CH:13]=[N:12]1
Reactant: O=C(O)c1ncoc1-c1ccccc1
Reactant: CC1(CCCCn2cc(N)cn2)OCCO1
Product: CC(=O)CCCCn1cc(NC(=O)c2ncoc2-c2ccccc2)cn1

Procedure:
Following general procedure B followed by either C or D, starting from 1-[4-(2-methyl-[1,3]dioxolan-2-yl)-butyl]-1H-pyrazol-4-ylamine and 5-phenyl-oxazole-4-carboxylic acid.
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][O:9][C:10]([C@H:12]1[CH2:17][CH2:16][C@H:15]([NH:18]C(OC(C)(C)C)=O)[CH2:14][CH2:13]1)=[O:11]>ClCCl>[CH3:8][O:9][C:10]([C@H:12]1[CH2:17][CH2:16][C@H:15]([NH2:18])[CH2:14][CH2:13]1)=[O:11]
Reactant: COC(=O)[C@H]1CC[C@H](NC(=O)OC(C)(C)C)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)[C@H]1CC[C@H](N)CC1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
Trifluoroacetic acid (13.47 mL, 19.94 mmol, 15.0 eq) is added at 0° C. to a stirred solution of trans-4-tert-butoxycarbonylamino-cyclohexanecarboxylic acid methyl ester (3.53 g, 11.66 mmol, 1.0 eq) in dichloromethane (100 mL). After 15 hours stirring at room temperature, the reaction mixture is extracted with dichloromethane (3×50 mL) and water (50 mL) and the pH is adjusted to 12 by the addition of a 1N sodium hydroxide aqueous solution. The combined organic layers are dried over sodium sulfate, filtered and concentrated to afford trans-4-amino-cyclohexanecarboxylic acid methyl ester as a yellow oil (1.53 g, 79% yield).
Reaction SMILES: [CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([C:21]3[NH:25][C:24]([C:26]4[S:27][C:28](/[CH:31]=[CH:32]/[C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:29][N:30]=4)=[CH:23][CH:22]=3)[CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.O1CCCC1>[C].[Pd].C(O)C>[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([C:21]3[NH:25][C:24]([C:26]4[S:27][C:28]([CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:29][N:30]=4)=[CH:23][CH:22]=3)[CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:9][CH:8]=2)(=[O:5])=[O:6])[CH2:3][CH2:2]1
Reactant: CCOC(=O)/C=C/c1cnc(-c2ccc(C(CC3CCOCC3)c3ccc(S(=O)(=O)C4CC4)cc3)[nH]2)s1
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: CCOC(=O)CCc1cnc(-c2ccc(C(CC3CCOCC3)c3ccc(S(=O)(=O)C4CC4)cc3)[nH]2)s1
Temperature: 25 °C
Reaction time: 48 h
Yield: 74.1 %

Procedure:
A mixture of ethyl (2E)-3-[2-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3-thiazol-5-yl]propenoate (0.78 g), 10% palladium carbon (containing 50% water, 0.15 g), tetrahydrofuran (10 mL) and ethanol (5 mL) was stirred under hydrogen atmosphere at room temperature for 2 days. The insoluble material was filtered off, and the filtrate was concentrated. The obtained residue was subjected to silica gel column chromatography, and the title compound (0.58 g, yield 79%) was obtained as a yellow amorphous solid from a fraction eluted with ethyl acetate-hexane (2:1, volume ratio). MS: 543 (MH+).
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[CH3:5][C:6]1([CH3:16])[CH:11]2[CH2:12][CH:7]1[CH2:8][CH:9]=[C:10]2[CH2:13][CH2:14][OH:15].C(N(CC)CC)C>ClCCl>[CH3:2][C:1]([O:15][CH2:14][CH2:13][C:10]1[C@H:11]2[C:6]([CH3:16])([CH3:5])[C@H:7]([CH2:12]2)[CH2:8][CH:9]=1)=[O:3]
Reactant: CC(=O)Cl
Reactant: CC1(C)C2CC=C(CCO)C1C2
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)OCCC1=CC[C@H]2C[C@@H]1C2(C)C
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
50 g of acetyl chloride (=0.64 mole) were slowly added dropwise to a solution of 100 g of (-)-nopol (=0.6 mole) and 130 ml of triethylamine (=0.93 mole) in 600 ml of dichloromethane while cooling in ice at a temperature of 5° to 10° C. The reaction mixture was subsequently stirred at 5° to 10° C. for a further 20 minutes. The reaction mixture was then further stirred without cooling until it had warmed to room temperature. To work up the reaction mixture, it was stirred into 800 ml of ice-water. The organic phase was separated, the aqueous phase was washed with 100 ml of dichloromethane, and the combined organic phases were washed to neutrality with saturated aqueous sodium bicarbonate solution and dried over sodium sulfate. The residue after removal of the dichloromethane by distillation was 130 g of crude product, from which (-)-nopyl acetate was isolated by fractional distillation. 98 g of (-)-nopyl acetate with a boiling point of 117°-119° C. (10 mm Hg) and a refractive index nD20 =1.4722 were obtained.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]4[O:21][CH2:20][O:19][C:17]4=[CH:18][C:13]=3[CH2:12][CH:11]([CH3:22])[N:10]([C:23](=[O:25])[CH3:24])[N:9]=2)=[CH:4][CH:3]=1.[C:26](OC(=O)C)(=[O:28])[CH3:27]>>[C:26]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]4[O:21][CH2:20][O:19][C:17]4=[CH:18][C:13]=3[CH2:12][CH:11]([CH3:22])[N:10]([C:23](=[O:25])[CH3:24])[N:9]=2)=[CH:4][CH:3]=1)(=[O:28])[CH3:27]
Reactant: CC(=O)N1N=C(c2ccc(N)cc2)c2cc3c(cc2CC1C)OCO3
Reactant: CC(=O)OC(C)=O
Product: CC(=O)Nc1ccc(C2=NN(C(C)=O)C(C)Cc3cc4c(cc32)OCO4)cc1
Temperature: 0 °C

Procedure:
1.3 g (4.4 mmol) of 1-(4-aminophenyl)-3-acetyl-4-methyl-7,8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepine were stirred at 20°-25° C. with 5 ml of acetic anhydride for one hour, then the yellow solution was poured into 100 g of ice-water and stirred until the decomposition of the excess anhydride became complete. The precipitate formed was filtered, washed with 3×10 ml of distilled water and dried to give 1.6 g of raw product. After recrystallization from 20 ml of benzene 1.50 g (89.85%) of the aimed product were obtained, m.p.: 158°-160° C. (decomp.).
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]=[C:12]([CH3:21])[O:13][C:14]=2[CH2:15][CH2:16][C:17]([O:19]C)=[O:18])=[CH:6][CH:5]=1.Cl>C(O)C.O>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[N:11]=[C:12]([CH3:21])[O:13][C:14]=2[CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:8][CH:9]=1
Reactant: COC(=O)CCc1oc(C)nc1-c1ccc(Cl)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: Cc1nc(-c2ccc(Cl)cc2)c(CCC(=O)O)o1
Reaction time: 0.5 h

Procedure:
2N Sodium hydroxide (5 ml) was added to a solution of methyl 4-(4-chlorophenyl)-2-methyloxazole-5-propionate (1.4 g) in ethanol (10 ml) and the mixture was allowed to stand at room temperature for 30 minute, diluted with water and adjusted to pH 2 with hydrochloric acid. The resulting crystalline precipitate was collected by filtration and recrystallized from ethanol to give crystals of 4-(4-chlorophenyl)-2-methyloxazole-5-propionic acid, yield 1.17 g (88.6%), m.p. 211°-212° C. The IR and NMR spectra of this compound were in complete agreement with those of the compound obtained in Example 5.
Reaction SMILES: [CH:1]1[CH:6]=[C:5]2[C:7]([OH:18])=[C:8]3[C:13](=[C:14]([OH:15])[C:4]2=[CH:3][CH:2]=1)[C:12](O)=[CH:11][CH:10]=[C:9]3O.[CH3:19][NH:20][CH2:21][CH2:22][NH2:23]>>[CH3:19][NH:20][CH2:21][CH2:22][NH:23][C:12]1[C:13]2[C:14](=[O:15])[C:4]3[C:5](=[CH:6][CH:1]=[CH:2][CH:3]=3)[C:7](=[O:18])[C:8]=2[C:9]([NH:23][CH2:22][CH2:21][NH:20][CH3:19])=[CH:10][CH:11]=1
Reactant: Oc1ccc(O)c2c(O)c3ccccc3c(O)c12
Reactant: CNCCN
Product: CNCCNc1ccc(NCCNC)c2c1C(=O)c1ccccc1C2=O
Temperature: 50 °C
Reaction time: 1 h

Procedure:
A mixture of 2.4 g. of leuco-quinizarin and 25 g. of de-aerated N-methylethylenediamine is heated at 50° C. with stirring under nitrogen for one hour. Heating at 50° C. is continued as air is bubbled into the mixture for 40 minutes. The mixture is evaporated to dryness, then re-evaporated twice from 25 ml. portions of ethanol. Crystallization of the residue from ethanol-ether at -70° C. gives 2.32 g. of crude solid which is recrystallized twice from carbon tetrachloride giving 1.92 g. of the desired product as dark blue crystals, mp. 131°-132° C.
Reaction SMILES: [CH3:1][CH2:2][Mg+].[Br-].CON(C)[C:8]([C:10]1[CH:11]=[CH:12][C:13]2[O:17][CH:16]=[N:15][C:14]=2[CH:18]=1)=[O:9]>C1COCC1>[O:17]1[C:13]2[CH:12]=[CH:11][C:10]([C:8](=[O:9])[CH2:2][CH3:1])=[CH:18][C:14]=2[N:15]=[CH:16]1
Reactant: CON(C)C(=O)c1ccc2ocnc2c1
Reactant: CC[Mg+]
Agent: [Br-]
Solvent: C1CCOC1
Product: CCC(=O)c1ccc2ocnc2c1
Reaction time: 2 h
Yield: 12 %

Procedure:
EtMgBr (1 M, 2.0 eq, 58 mL) was added to a solution of N-methoxy-N-methylbenzo[d]oxazole-5-carboxamide (6 g, 1.0 eq) in dry THF at 0° C., Once addition was complete, the mixture was stirred for 2 h. The reaction mixture was quenched with saturated NH4Cl and extracted with EtOAc. The extract was dried, concentrated, and purified by column chromatography with petroleum ether:EtOAc=1:1 to give the desired product (0.6 g, 12%)
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([N+:20]([O-])=O)[CH:15]=3)[N:9]=2)[CH:5]=[C:4]([C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=2)[CH:3]=1.[H][H]>C1COCC1.CCO.[Pd]>[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([C:14]3[CH:15]=[C:16]([NH2:20])[CH:17]=[CH:18][CH:19]=3)[N:9]=2)[CH:5]=[C:4]([C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:30])[F:31])=[CH:25][CH:24]=2)[CH:3]=1
Reactant: [H][H]
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2ccnc(-c3cccc([N+](=O)[O-])c3)n2)n1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2ccnc(-c3cccc(N)c3)n2)n1
Yield: 76.7 %

Procedure:
A mixture of 4-[6-methyl-4-(4-trifluoromethyl-phenyl)-pyridin-2-yl]-2-(3-nitro-phenyl)-pyrimidine (example 322) (2.1 g, 4.81 mmol) in THF-EtOH 1:1 (100 mL) and 10% palladium on carbon (1 mol %) was hydrogenated (1 bar hydrogen) at 23° C. for 2 h. The catalyst was filtered off, washed with EtOH and the filtrate was completely evaporated totally to leave a crude product, which was purified by silica gel column chromatography with heptane/EtOAc, followed by trituration with diethyl ether to give the title compound as an off-white solid (1.5 g, 76%). MS (ISP) 407.4 [(M+H)+]; mp 167° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:10][C:11]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=O)=[CH:5][C:4]=1[CH3:25].P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:27].C1(C)C(C)=CC=CC=1>C1CCCCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:10][C:11]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[S:27])=[CH:5][C:4]=1[CH3:25]
Reactant: COc1ccc(C(=CC(=O)N2CCOCC2)c2ccccc2)cc1C
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: Cc1ccccc1C
Solvent: C1CCCCC1
Product: COc1ccc(C(=CC(=S)N2CCOCC2)c2ccccc2)cc1C

Procedure:
6.75 g (20 mmols) of 3-(4-methoxy-3-methylphenyl)-3-phenylacrylic acid morpholide and 2.22 g (10 mmols) of finely ground phosphorus pentasulfide were refluxed unit 50 ml of absolute xylene for 3 horus. After cooling, the insoluble matter was filtered off, and the filtrate was washed with water, dried and concentrated by evaporation in vacuo. This concentrate was purified on a silica gel column. Elution was carried out first with toluene and then with a toluene/diisopropylether mixture in the proportions 90:10, then in the proportions 80:20. The fractions containing the substance with Rf 0.59 (toluene/diisopropylether 1:1) were concentrated by evaporation in vacuo, and the yellow oil obtained thereby was dissolved in cyclohexane, while heating. Upon cooling, the desired substance crystallized out.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:6]([CH2:16]O)=[C:5]2[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.S(Cl)(Cl)=O.[C:28]1(=[O:38])[NH:32][C:31](=[O:33])[C:30]2=[CH:34][CH:35]=[CH:36][CH:37]=[C:29]12.[K]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:6]([CH2:16][N:32]1[C:28](=[O:38])[C:29]3[C:30](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:31]1=[O:33])=[C:5]2[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: CC(C)Cc1nc2ccc(Cl)cc2c(-c2ccccc2)c1CO
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: O=S(Cl)Cl
Solvent: Cc1ccccc1
Product: CC(C)Cc1nc2ccc(Cl)cc2c(-c2ccccc2)c1CN1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 60 h
Yield: 56.2 %

Procedure:
To a solution of (6-chloro-2-isobutyl-4-phenylquinolin-3-yl)methanol (0.70 g, 2.15 mmol) in toluene (15 ml) was added thionyl chloride (0.31 ml, 4.3 mmol), and the mixture was heated under reflux for 1 hr. The reaction mixture was partitioned between ethyl acetate (100 ml) and saturated aqueous sodium hydrogen carbonate (50 ml). The organic layer was washed with saturated brine (20 ml) and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was dissolved in N,N-dimethylformamide (10 ml). Thereto was added potassium phthalimide (0.6 g, 3.2 mmol) and the mixture was stirred at room temperature for 2.5 days. The reaction mixture was partitioned between ethyl acetate (100 ml) and saturated aqueous sodium hydrogen carbonate (50 ml)-water (50 ml). The aqueous layer was extracted with ethyl acetate (50 ml) and the extract and the organic layer were combined. The mixture was washed twice with water (50 ml) and then saturated brine (50 ml), and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel column chromatography to give 2-[(6-chloro-2-isobutyl-4-phenylquinolin-3-yl)methyl]-1-H-isoindole-1,3(2H)-dione (0.55 g, yield 57%) as an orange oil.
Reaction SMILES: [CH3:1][P:2]([CH2:5][CH:6]([CH2:11][C:12]([O:14]C)=[O:13])[C:7]([O:9]C)=[O:8])([CH3:4])=[O:3]>O>[CH3:1][P:2]([CH2:5][CH:6]([CH2:11][C:12]([OH:14])=[O:13])[C:7]([OH:9])=[O:8])([CH3:4])=[O:3]
Reactant: COC(=O)CC(CP(C)(C)=O)C(=O)OC
Solvent: O
Product: CP(C)(=O)CC(CC(=O)O)C(=O)O
Yield: 91.8 %

Procedure:
80 g (0.34 mol) of dimethyl dimethylphosphinylmethylsuccinate are heated to reflux with a few drops of concentratedhydrochloric acid and 80 ml of water. Methanol slowly distils over a 70 cm silvered shell Vigreux column and at the same time a further 20 g of water are added dropwise. When the reaction is completed, the batch crystallizes. After addition of isopropanol, the mixture is stirred for several hours then filtered off by suction and dried. 65 g of dimethylphosphinylmethylsuccinic acid are obtained having a melting point of 139°-141° C. This corresponds to a yield of 92% of theory.
Reaction SMILES: Cl.[CH3:2][N:3]([CH3:8])[CH2:4][CH2:5][O:6][NH2:7].[CH:9]([C:11]1[CH:16]=[CH:15][N:14]2[C:17]([C:20]3[CH:21]=[C:22]([C:26]4[CH:30]=[CH:29][S:28][C:27]=4[C:31]#[N:32])[CH:23]=[CH:24][CH:25]=3)=[CH:18][N:19]=[C:13]2[CH:12]=1)=O>>[CH3:2][N:3]([CH3:8])[CH2:4][CH2:5][O:6][N:7]=[CH:9][C:11]1[CH:16]=[CH:15][N:14]2[C:17]([C:20]3[CH:21]=[C:22]([C:26]4[CH:30]=[CH:29][S:28][C:27]=4[C:31]#[N:32])[CH:23]=[CH:24][CH:25]=3)=[CH:18][N:19]=[C:13]2[CH:12]=1
Reactant: CN(C)CCON
Reactant: N#Cc1sccc1-c1cccc(-c2cnc3cc(C=O)ccn23)c1
Agent: Cl
Product: CN(C)CCON=Cc1ccn2c(-c3cccc(-c4ccsc4C#N)c3)cnc2c1

Procedure:
The title compound was prepared in a similar manner to that described in Example 14 using O-(2-dimethylaminoethyl)hydroxylamine hydrochloride (144 mg, 0.82 mmol) and 3-[3-(7-formylimidazo[1,2-α]pyridin-3-yl)phenyl]thiophene-2-carbonitrile (90 mg, 0.27 mmol) to afford a yellow solid (42 mg, 38%), essentially as a single geometric isomer, m.p. 74-75° C. 1H NMR (360 MHz, CDCl3) δH 2.33 (6H, s), 2.67-2.71 (2H, m), 4.30-4.34 (2H, m), 7.33-7.37 (2H, m), 7.63-7.70 (4H, m), 7.79 (1H, s), 7.91 (1H, s), 8.15 (1H, s), 8.45 (1H, d, J 7); m/z (ES+) 416 (M++H).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH:13]=1.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(N(CC)CC)C>CO.[Pt](=O)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:9])[F:10])=[CH:4][C:3]=1[CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1
Reactant: CC(C)(C)OC(=O)N1CC=C(c2cc(C(F)(F)F)ccc2Br)CC1
Agent: O=[Pt]=O
Agent: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Solvent: CCN(CC)CC
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(c2cc(C(F)(F)F)ccc2Br)CC1
Reaction time: 4 h
Yield: 56.7 %

Procedure:
A solution of tert-butyl 4-(2-bromo-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate J, 8.45 g, 20.80 mmol) and platinum(IV) oxide (0.472 g, 2.080 mmol) in 40 mL MeOH was placed under 45 psi (4559.6 kpa) H2 for 2 hours. The reaction mixture was filtered through a plug of diatomaceous earth and was concentrated. The resulting residue was taken up in 10 mL THF, was treated with di-tert-butyl dicarbonate (10.40 ml, 10.40 mmol) followed by triethylamine (2.90 ml, 20.80 mmol) and was allowed to stir for 4 hours. Concentration and purification of the resulting residue by silica gel column chromatography (0 to 10% EtOAc/heptane) gave tert-butyl 4-(2-bromo-5-(trifluoromethyl)phenyl)piperidine-1-carboxylate (4.812 g, 11.79 mmol) as a clear oil. [M+Na]+=432.0