Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:15]=[CH:14][C:13]([C:16]2([CH3:21])OCC[O:17]2)=[CH:12][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].Cl(O)(=O)(=O)=O.[OH-].[Na+]>C(O)C>[C:16]([C:13]1[CH:14]=[CH:15][C:2]([NH2:1])=[C:3]([CH:12]=1)[C:4]([C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)=[O:5])(=[O:17])[CH3:21]
Reactant: CC1(c2ccc(N)c(C(=O)c3ccccc3)c2)OCCO1
Agent: [Na+]
Agent: [O-][Cl+3]([O-])([O-])O
Agent: [OH-]
Solvent: CCO
Product: CC(=O)c1ccc(N)c(C(=O)c2ccccc2)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 93.5 %

Procedure:
2-Amino-5-(2-methyl-1,3-dioxolan-2-yl)benzophenone (1.0 g, 3.54 m mol) was dissolved in 30 ml absolute ethanol. To this was added 1M perchloric acid (14 ml). The resulting mixture was stirred at room temperature for 18 hrs. The mixture was made basic with 3N sodium hydroxide solution and then extracted with several portions of methylene chloride. The combined methylene chloride extracts were washed with water, dried with anhydrous sodium sulfate, and evaporated to yield a yellow product (0.79 g) of mp. 158°-161° C. A portion of the product was recrystallized from a mixture of methylene chloride and hexane to yield material of mp. 158°-162° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]([CH3:20])[C:10]2=[O:21])=[CH:4][C:3]=1[S:22]([N:25]=[C:26]=[O:27])(=[O:24])=[O:23].[CH2:28]([OH:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>ClCCCl.C(Cl)Cl>[CH2:28]([O:35][C:26](=[O:27])[NH:25][S:22]([C:3]1[CH:4]=[C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]([CH3:20])[C:10]2=[O:21])[C:6]([F:8])=[CH:7][C:2]=1[Cl:1])(=[O:24])=[O:23])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: OCc1ccccc1
Reactant: Cn1c(C(F)(F)F)cc(=O)n(-c2cc(S(=O)(=O)N=C=O)c(Cl)cc2F)c1=O
Solvent: ClCCl
Solvent: ClCCCl
Product: Cn1c(C(F)(F)F)cc(=O)n(-c2cc(S(=O)(=O)NC(=O)OCc3ccccc3)c(Cl)cc2F)c1=O

Procedure:
With stirring, 0.6 g (1.4 mmol) of 2-chloro-4-fluoro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-trifluoromethyl-(2H)-pyrimidin-1-yl]benzenesulfonylisocyanate in 1,2-dichloroethane was added to a solution of 0.15 g (1.4 mmol) of benzyl alcohol in methylene chloride, and the reaction mixture was stirred overnight. Removal of the solvent and customary purification methods gave 0.4 g (52% of theory) of the title compound as a colorless solid (m.p.: 231-232° C.).
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[C:6]#[N:7].Cl[C:12]1[CH:22]=[C:16]2[N:17]([CH3:21])[CH2:18][CH2:19][CH2:20][N:15]2[C:14](=[O:23])[N:13]=1>>[CH3:21][N:17]1[CH2:18][CH2:19][CH2:20][N:15]2[C:14](=[O:23])[N:13]=[C:12]([O:1][CH2:2][C:3]3[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=3)[C:6]#[N:7])[CH:22]=[C:16]12
Reactant: N#Cc1cccc(CO)c1
Reactant: CN1CCCn2c1cc(Cl)nc2=O
Product: CN1CCCn2c1cc(OCc1cccc(C#N)c1)nc2=O

Procedure:
The title compound or its salt was prepared by a procedure similar to that described for E2 starting from 3-(hydroxymethyl)benzonitrile and 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one.
Reaction SMILES: [CH3:1][C:2]([CH3:10])([C:4](=[O:9])[CH2:5][C:6](=O)[CH3:7])[CH3:3].S([O-])([O-])(=O)=O.[Na+].[Na+].[CH:18]([NH2:21])([CH3:20])[CH3:19]>C1(C)C=CC=CC=1>[CH3:1][C:2]([CH3:10])([C:4](=[O:9])[CH2:5][CH:6]([NH:21][CH:18]([CH3:20])[CH3:19])[CH3:7])[CH3:3]
Reactant: CC(=O)CC(=O)C(C)(C)C
Reactant: CC(C)N
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CC(C)NC(C)CC(=O)C(C)(C)C
Yield: 84.4 %

Procedure:
To a solution of 15.00 g (105.49 mmol) 2,2-dimethyl-3,5-hexanedione in 50 mL of toluene loaded with 30.00 g sodium sulfate was added 12.47 g (210.97 mmol) isopropylamine. The mixture was refluxed for 4 days. Removal of toluene resulted in a yellow oil, which was subjected to vacuum transfer at 80° C. under 125 mTorr. 16.5 g of clear oil was obtained with a yield of 84%. 1H NMR (500 MHz, C6D6): δ=11.50 (s, 1H), 5.16 (s, 1H), 3.11 (m, 1H), 1.49 (s, 3H), 1.31 (s, 9H), 0.79 (d, 6H).
Reaction SMILES: C([O:8][C:9]1[C:14](=[O:15])[CH:13]=[C:12]([CH3:16])[N:11]([CH:17]2[CH2:19][CH2:18]2)[C:10]=1[C:20]([NH:22][CH2:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)=[O:21])C1C=CC=CC=1.[H][H]>C(O)C.CO.[Pd]>[CH:24]1([CH2:23][NH:22][C:20]([C:10]2[N:11]([CH:17]3[CH2:19][CH2:18]3)[C:12]([CH3:16])=[CH:13][C:14](=[O:15])[C:9]=2[OH:8])=[O:21])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]1
Reactant: Cc1cc(=O)c(OCc2ccccc2)c(C(=O)NCC2CCCCC2)n1C1CC1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Solvent: CCO
Product: Cc1cc(=O)c(O)c(C(=O)NCC2CCCCC2)n1C1CC1
Temperature: 25 °C
Yield: 63 %

Procedure:
A mixture of 3-(benzyloxy)-N-(cyclohexylmethyl)-1-cyclopropyl-6-methyl-4-oxo-1,4-dihydropyridine-2-carboxamide (2.0 g, 4.8 mmol), Pd/C (10% wet, 0.45 g) in ethanol (150 mL) was hydrogenated in a Parr apparatus at 50 psi of hydrogen pressure for 16 h. The reaction mixture was filtered over a pad of Celite® and the Celite® was thoroughly washed with EtOH (25 mL). Evaporation of the solvent afforded a pale pink solid. The solid was dissolved in hot methanol, then cooled to RT as solid product precipitated out. The solid was collected by suction filtration. The mother liquor was concentrated in vacuo and the residual solid was again dissolved in hot methanol and cooled to RT to precipitate out the product, which was then collected. This process was repeated one more time. The three combined white solid fractions weighed 0.95 g (63% yield).
Reaction SMILES: [CH:1]1([C:7]2[C:15]3[C:14](=[O:16])[NH:13][C:12]([C:17]4[CH:22]=[CH:21][C:20]([NH:23][CH3:24])=[CH:19][C:18]=4[O:25][CH3:26])=[N:11][C:10]=3[N:9]([CH3:27])[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:28][S:29](Cl)(=[O:31])=[O:30].C(=O)([O-])O.[Na+]>N1C=CC=CC=1>[CH:1]1([C:7]2[C:15]3[C:14](=[O:16])[NH:13][C:12]([C:17]4[CH:22]=[CH:21][C:20]([N:23]([CH3:24])[S:29]([CH3:28])(=[O:31])=[O:30])=[CH:19][C:18]=4[O:25][CH3:26])=[N:11][C:10]=3[N:9]([CH3:27])[N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CNc1ccc(-c2nc3c(c(C4CCCCC4)nn3C)c(=O)[nH]2)c(OC)c1
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Product: COc1cc(N(C)S(C)(=O)=O)ccc1-c1nc2c(c(C3CCCCC3)nn2C)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 20 h
Yield: 87.3 %

Procedure:
To a 3 ml pyridine solution of 91.8 mg (0.25 mmol) of the compound obtained in Example 47, 23.2 μl (0.3 mmol) of methanesulfonyl chloride was added, and the mixture was stirred at room temperature for 20 hours. Then, an aqueous solution of sodium hydrogen carbonate was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was washed with water and a saturated aqueous solution of sodium chloride. After the washed layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/1˜only ethyl acetate) to obtain 97.2 mg (87%) of the captioned compound.
Reaction SMILES: [C:1]([CH:3]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=1)[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])#[N:2]>C(O)C.Cl.[H][H].[OH-].[OH-].[Pd+2]>[NH2:2][CH2:1][CH:3]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=1)[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6]
Reactant: CCOC(=O)CC(C#N)c1cccc(OC)c1
Reactant: [H][H]
Agent: [Pd+2]
Agent: Cl
Agent: [OH-]
Solvent: CCO
Product: CCOC(=O)CC(CN)c1cccc(OC)c1
Yield: 31.4 %

Procedure:
To a solution of ethyl 3-cyano-3-(3-methoxyphenyl)propanoate (11.9 g) in ethanol (41 ml), 12 N hydrochloric acid (3.8 ml) and 20% palladium hydroxide on carbon (2.10 g) was added, and the mixed solution was stirred in hydrogen atmosphere at room temperature for 15 hours. The solvent was removed by evaporation under reduced pressure, and resulting crude product was purified by column chromatography (neutral OH type silica gel, methanol/chloroform=2 to 9%) to give ethyl 4-amino-3-(3-methoxyphenyl)butanoate (3.80 g).
Reaction SMILES: Br.[Br:2][CH2:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[N:9][NH:10]2)=[CH:6][CH:5]=1.[O:13]1[CH:18]=[CH:17][CH2:16][CH2:15][CH2:14]1>C1COCC1.C(Cl)Cl>[Br:2][CH2:3][C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[N:9][N:10]2[CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18][O:13]2)=[CH:6][CH:5]=1
Reactant: BrCc1ccc2cn[nH]c2c1
Reactant: C1=COCCC1
Agent: Br
Solvent: ClCCl
Solvent: C1CCOC1
Product: BrCc1ccc2cnn(C3CCCCO3)c2c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 52 %

Procedure:
A yellow suspension of 6-(bromomethyl)-1H-indazole hydrogen bromide (9.0 g, 43 mmol) (4-5) and 3,4-dihydro-2H-pyran (7.2 g, 86 mmol) in THF (200 mL) was heated at its reflux temperature for 2 hours. After cooling down to room temperature, the reaction mixture was stirred at room temperature for 12 hours under nitrogen. The reaction solution was diluted with methylene chloride (500 mL), washed with saturated NaHCO3, water and brine. After drying (MgSO4), the solvent was removed under vacuum to give a yellow oil. Flash chromatography yielded the title compound (6.6 g, 72%). TLC Rf 0.52 (80:20 of hexane-ethyl acetate); MS (electrospray) 295, 297 (M+1); 1H N MR (CDCl3) δ1.57-1.84 (m, 3H), 2.16 (m, 2H), 2.55 (m, 1H), 3.75 (m, 1H), 4.01 (m, 1H), 4.65 (s, 2H), 5.71 (d, 1H, J=9.2 Hz), 7.44 (d, 1H, J=8.8 Hz), 7.59 (d, 1H, J=8.8 Hz), 7.73 (s, 1H), 8.00 (s, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1.[CH2:23]([N:26]=[C:27]=[O:28])[CH2:24][CH3:25].O>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:17]=[CH:18][C:19]([NH:22][C:27]([NH:26][CH2:23][CH2:24][CH3:25])=[O:28])=[CH:20][CH:21]=1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Reactant: CCCN=C=O
Solvent: O
Solvent: CN(C)C=O
Product: CCCNC(=O)Nc1ccc(Oc2ccnc3cc(OC)c(OC)cc23)cc1
Temperature: 80 °C
Reaction time: 24 h
Yield: 84 %

Procedure:
6,7-Dimethoxy-4-(4-aminophenoxy)quinoline (54 mg) was dissolved in N,N-dimethylformamide (3 ml), propyl isocyanate (0.2 ml) was added, and the admixture was stirred at 80° C. for 24 hours. Water was added to the reaction mixture, the admixture was extracted 2 times with ethyl acetate, and the organic layer was then washed with brine and dried with anhydrous sodium sulfate. The solvent was removed by reduced-pressure distillation and the resulting residue was purified by column chromatography on silica gel eluting with chloroform/acetone (10/1) to obtain 59 mg of the title compound (yield: 84%).
Reaction SMILES: [O:1]=[C:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:11]([OH:13])=O)[C:5]=2[CH2:4][CH2:3]1.C(N=C=NC(C)C)(C)C.O.ON1C2C=CC=CC=2N=N1.[NH2:34][CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37]>CN(C)C=O>[O:1]=[C:2]1[C:10]2[C:5](=[C:6]([C:11]([NH:34][CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[O:13])[CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1
Reactant: O=C(O)c1cccc2c1CCC2=O
Reactant: CC(C)(C)OC(=O)CN
Agent: CC(C)N=C=NC(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)CNC(=O)c1cccc2c1CCC2=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of Example 5 (250 mg, 1.42 mmol) in N,N-dimethylformamide (4 mL) was added 1,3-diisopropylcarbodiimide (0.268 mL, 1.70 mmol), 1-hydroxybenzotriazole hydrate (58 mg, 0.4 mmol), and t-butyl glycinate (223 mg, 1.7 mmol). The mixture was stirred at room temperature overnight, quenched with saturated aqueous sodium bicarbonate, and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel using hexane/ethyl acetate (50:1) as the mobile phase to provide the desired product. MS (APCI): m/z 290 (M+H)+.
Reaction SMILES: [I-].[Br:2][C:3]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[C:9]2[C:4]=1[CH:5]=[CH:6][N+:7]([CH3:16])=[CH:8]2.[BH3-]C#N.[Na+]>CO>[Br:2][C:3]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[C:9]2[C:4]=1[CH2:5][CH2:6][N:7]([CH3:16])[CH2:8]2
Reactant: C[n+]1ccc2c(Br)ccc([N+](=O)[O-])c2c1
Agent: [BH3-]C#N
Agent: [I-]
Agent: [Na+]
Solvent: CO
Product: CN1CCc2c(Br)ccc([N+](=O)[O-])c2C1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
Into a 500 mL 3-necked round bottom flask was placed a solution of Ni(NO3)2.6H2O (12.6 g, 43.33 mmol) in CH3OH (200 mL). To the mixture was added 5-bromo-8-nitro-N-methylisoquinolinium iodide (33.33 g, 84.38 mmol). To the above was added NaCNBH3 (10.6 g, 168.68 mmol) in several batches. The resulting solution was allowed to react, with stirring, for 5 hours while the temperature was maintained at room temperature. The reaction progress was monitored by TLC (ethyl acetate/petroleum ether=1:5). The resulting solution was concentrated by evaporation under vacuum using a rotary evaporator. The residue was dissolved with 800 mL of H2O. Adjustment of the pH to 8-10 was accomplished by the addition of NaOH (5%). A filtration was performed. The resulting solution was extracted 2 times with 800 mL of ethyl acetate and the organic layers combined and dried over Na2SO4. The residue was purified by eluting through a column with a 1:5 ethyl acetate/petroleum ether solvent system. This resulted in 19.3 g (83%) of 5-bromo-2-methyl-8-nitro-1,2,3,4-tetrahydroisoquinoline as a yellow solid.
Reaction SMILES: C[O:2][C:3]([C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][C:8]=2[N+:14]([O-:16])=[O:15])=[O:4].[OH-].[Na+].Cl>O1CCCC1.O>[N+:14]([C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:7]=1[NH:6][C:5]([C:3]([OH:4])=[O:2])=[CH:13]2)([O-:16])=[O:15]
Reactant: COC(=O)c1cc2cccc([N+](=O)[O-])c2[nH]1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1cc2cccc([N+](=O)[O-])c2[nH]1
Temperature: 25 °C
Reaction time: 3 h
Yield: 98.7 %

Procedure:
7-Nitro-1H-indole-2-carboxylic acid methyl ester (13 g, 59 mmol) prepared in Preparation 17 was dissolved in a solvent mixture of tetrahydrofuran and water (1:1, 300 mL), to which was added 1N aqueous sodium hydroxide solution (180 mL, 177 mmol). The mixture was stirred for 3 h at room temperature, and excess 6N hydrochloric acid solution was added thereto. The reaction mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed by distillation under reduced pressure, and the residue was dried to give the title compound (12 g, Yield 99%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]([OH:10])=O)[CH:2]=1.Cl.[C:12]1([C:18]2([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:26]3[CH:22]([CH2:23][NH:24][CH2:25]3)[C:21](=[O:27])[CH2:20][CH2:19]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>ClCCl>[C:28]1([C:18]2([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:26]3[CH:22]([CH2:23][N:24]([C:8](=[O:10])[CH2:7][C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)[CH2:25]3)[C:21](=[O:27])[CH2:20][CH2:19]2)[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1
Reactant: O=C(O)Cc1cccnc1
Reactant: O=C1CCC(c2ccccc2)(c2ccccc2)C2CNCC12
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C1CCC(c2ccccc2)(c2ccccc2)C2CN(C(=O)Cc3cccnc3)CC12
Reaction time: 0.5 h
Yield: 44.9 %

Procedure:
N,N'-Carbonyldiimidazole (0.81 g) is added to a solution of 2-(3-pyridyl)acetic acid (0.685 g) in dry dichloromethane (15 cc), cooled to +5° C. The mixture is stirred for 30 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (1.6 g) and triethylamine (0.7 cc) in dichloromethane (10 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours and then concentrated to dryness under reduced pressure (2.7 kPa). The residue is taken up in a mixture of ethyl acetate (100 cc) and water (75 cc). The organic phase is washed with saturated sodium chloride solution (50 cc), dried over magnesium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a basic alumina column (diameter 2 cm, height 15 cm), eluting with ethyl acetate and collecting 50 cc fractions. Fractions 4 to 24 are concentrated to dryness under reduced pressure (2.7 kPa). The crystals obtained are recrystallized from acetonitrile (cc) to give (3aRS,7aRS)-7,7-diphenyl-2-[2-(3-pyridyl)acetyl]-4-perhydroisoindolone (0.9 g) in the form of white crystals melting at 208° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C:20](=O)[C:19]3[C:14](=[CH:15][C:16]([OH:24])=[C:17]([CH2:22][CH3:23])[CH:18]=3)[O:13][CH:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].O.[NH2:26][NH2:27]>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C:20]([C:19]3[CH:18]=[C:17]([CH2:22][CH3:23])[C:16]([OH:24])=[CH:15][C:14]=3[OH:13])=[N:26][NH:27][CH:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: NN
Reactant: CCc1cc2c(=O)c(-c3ccc(OC)c(OC)c3)coc2cc1O
Solvent: CCO
Solvent: O
Product: CCc1cc(-c2n[nH]cc2-c2ccc(OC)c(OC)c2)c(O)cc1O
Yield: 61.1 %

Procedure:
This compounds was synthesised in the same manner as described above. 3-(3,4-Dimethoxy-phenyl)-6-ethyl-7-hydroxy-chromen-4-one (0.25 g, 0.77 mmol), hydrazine hydrate (4 ml), ethanol (10 ml). The crude solid product was columned to give 4-[4-(3,4-Dimethoxy-phenyl)-1H-pyrazol-3-yl]-6-ethyl-benzene-1,3-diol as a white solid (0.16 g, 61.1%); Rf 0.33 Cf SM 0.71 ethyl acetate/hexane (75/25).
Reaction SMILES: [C:1]([O:5][C:6]([C@@H:8]1[CH2:12][S:11][CH:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])[NH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][C:21]1[CH:22]=[C:23]([NH:27][C:28](=[O:34])[NH:29][CH2:30][C:31](O)=[O:32])[CH:24]=[CH:25][CH:26]=1.C1(N=C=NC2CCCCC2)CCCCC1.[K+].[Br-]>CCCCCCC.CN(C=O)C>[CH3:20][C:21]1[CH:22]=[C:23]([NH:27][C:28](=[O:34])[NH:29][CH2:30][C:31]([N:9]2[C@H:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:12][S:11][C@@H:10]2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])=[O:32])[CH:24]=[CH:25][CH:26]=1
Reactant: Cc1cccc(NC(=O)NCC(=O)O)c1
Reactant: CC(C)(C)OC(=O)[C@@H]1CSC(c2ccccc2F)N1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: [Br-]
Agent: [K+]
Solvent: CCCCCCC
Solvent: CN(C)C=O
Product: Cc1cccc(NC(=O)NCC(=O)N2[C@@H](c3ccccc3F)SC[C@H]2C(=O)OC(C)(C)C)c1
Yield: 20.1 %

Procedure:
The operation is carried out in a fashion similar to that described in Example 33, but starting from 3.5 g of tert-butyl-(2RS,4R)-2-(2-fluorophenyl)-4-thiazolidinecarboxylate, 2.3 g of 2-[3-(3-methylphenyl)ureido]acetic acid and 2.3 g of N,N'-dicyclohexylcarbodiimide. After vigorous stirring in heptane, 1.05 g of tert-butyl (2R,4R)-3-{2-[3-(3-methylphenyl)ureido]acetyl}-2-(2-fluorophenyl)-4-thiazolidinecarboxylate are thus obtained in the form of a white solid, melting at 107° C. ([α]D20 =+61.8°±1.5° (C=0.66%; DMF)) [proton NMR (200 MHz, DMSO D6, δ in ppm), 2 rotamers at room temperature, peak coalescence at 120° C., characteristic chemical shifts at 120° C.: 2.2 (bs, 3H, CH3); 6.7 (bd, 1H, N--C6H4 --C in position 4 or 6); 7.1 to 7.40 (m, 6H, aromatic); 7.9 (bm, 1H, C6H4F in position 3). Infrared spectrum (KBr), characteristics bands in cm-1 : 3370, 2975, 2925, 1735, 1645, 1615, 1590, 1560, 1490, 1460, 1370, 1150, 775, 760, 690].
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([S:38][CH:39]([C:41]5[N:42]([CH2:46][CH2:47][CH3:48])[CH:43]=[CH:44][N:45]=5)[CH3:40])=[CH:34][CH:33]=4)=[O:30])=[CH:20][C:19]=3[CH:49]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].ClC1C=CC=C(C(OO)=[O:58])C=1>ClCCl>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:27])[CH3:28])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:33]=[CH:34][C:35]([S:38]([CH:39]([C:41]5[N:42]([CH2:46][CH2:47][CH3:48])[CH:43]=[CH:44][N:45]=5)[CH3:40])=[O:58])=[CH:36][CH:37]=4)=[O:30])=[CH:20][C:19]=3[CH:49]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(SC(C)c4nccn4CCC)cc2)CCN3CC(C)C)cc1
Solvent: ClCCl
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(S(=O)C(C)c4nccn4CCC)cc2)CCN3CC(C)C)cc1
Yield: 81.6 %

Procedure:
To a solution of 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[[1-[1-propylimidazol-2-yl]ethyl]sulfanyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (170 mg) in dichloromethane (10 ml) was added dropwise 70% solution of 3-chloroperbenzoic acid (92 mg) in dichloromethane (10 ml) at −78° C. The reaction vessel was removed from a dry ice-acetone bath, and an aqueous solution of sodium thiosulfate was added to the reaction vessel with strongly stirring. The mixture was allowed to be at room temperature, stirred for 30 minutes, and extracted with ethyl acetate. The organic layer was washed with an aqueous solution of saturated sodium bicarbonate, and saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was separated and purified by basic silica gel column chromatography (ethyl acetate), to give 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[[1-[1-propylimidazol-2-yl]ethyl]sulfinyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (142 mg) (Compound 396) as yellow amorphous.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1.CS(C)=O.[OH-].[Na+].[CH:16]([O:18][CH2:19][CH2:20]Cl)=[CH2:17]>O>[CH:16]([O:18][CH2:19][CH2:20][O:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1)=[CH2:17]
Reactant: C=COCCCl
Reactant: OCc1ccc(O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CS(C)=O
Product: C=COCCOc1ccc(CO)cc1
Yield: 55 %

Procedure:
In a 500 mL three-neck round-bottom flask equipped with an overhead stirrer and a reflux condenser were placed 21.7 g of 4-hydroxybenzyl alcohol, and 65 mL of dimethyl sulfoxide. To this solution was slowly added 6.99 g of NaOH, while keeping the temperature below 45° C. After the solution was completed, 20.4 mL of 2-chloroethyl vinyl ether was added slowly while keeping the temperature at 60° C. The reaction mixture was heated at this temperature for 2 hours, and the progress of the reaction was followed by GC. After cooling, the reaction product was added dropwise to 500 mL of water. The precipitated product was then filtered and redissolved in 500 mL of diethyl ether. The ether layer was washed one time with 100 mL of 3% aqueous NaOH and two times with 100 mL portions of distilled water. The ether layer was dried with sodium sulfate, filtered and evaporated. A 55% yield of 2-(4-hydroxymethyl-phenoxy)ethyl vinyl ether was obtained.