Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: S(O[CH2:6][CH2:7][NH:8][C:9](=[O:29])[CH:10]([OH:28])[CH:11]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[N+:19]([O-:21])=[O:20])(C)(=O)=O.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[N+:19]([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[O:12][CH:11]([CH:10]1[O:28][CH2:6][CH2:7][NH:8][C:9]1=[O:29])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([O-:21])=[O:20]
Reactant: CS(=O)(=O)OCCNC(=O)C(O)C(Oc1ccccc1[N+](=O)[O-])c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C1NCCOC1C(Oc1ccccc1[N+](=O)[O-])c1ccccc1
Temperature: 50 °C
Yield: 38.7 %

Procedure:
To a solution of 4.24 g of N-(2-mesyloxyethyl)-3-phenyl-2-hydroxy-3-(2-nitro-phenoxy)-propionamide in 150 ml of DMF there was added 1.38 g of potassium carbonate. The stirred mixture was heated at 50° C. for 5 hours, then poured into water and extracted with ethyl acetate. The dehydrated organic extracts were evaporated to dryness and the residue was chromatographed on silica gel, to obtain 1.27 g of 2-[α-(2-nitro-phenoxy)-benzyl]-morpholin-3-one.
Reaction SMILES: [CH:1]([S:4][C:5]1[S:6][C:7]([C:18]([O:20]CC)=[O:19])=[C:8]2[CH2:17][CH2:16][C:11]3[N:12]=[C:13]([CH3:15])[O:14][C:10]=3[C:9]=12)([CH3:3])[CH3:2].[OH-].[Na+].O.Cl>C(O)C>[CH:1]([S:4][C:5]1[S:6][C:7]([C:18]([OH:20])=[O:19])=[C:8]2[CH2:17][CH2:16][C:11]3[N:12]=[C:13]([CH3:15])[O:14][C:10]=3[C:9]=12)([CH3:3])[CH3:2]
Reactant: CCOC(=O)c1sc(SC(C)C)c2c1CCc1nc(C)oc1-2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Cc1nc2c(o1)-c1c(SC(C)C)sc(C(=O)O)c1CC2
Temperature: 50 °C
Reaction time: 1 h
Yield: 87.6 %

Procedure:
Ethyl 4,5-dihydro-8-isopropylthio-2-methylthieno[3,4-g]benzoxazole-6-carboxylate (0.71 g) was dissolved in ethanol (30 ml); a 2 N aqueous solution of sodium hydroxide (2.1 ml) was added at 50° C. After the reaction mixture was stirred at 50° C. for 1 hour, the solution obtained was poured over water, acidified with 1 N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with water and dried (MgSO4), after which the solvent was distilled off to yield 4,5-dihydro-8-isopropylthio-2-methylthieno[3,4-g]benzoxazole-6-carboxylic acid (0.57 g, 66%), which was then recrystallized from ethyl acetate-hexane. Yellow prisms. Melting point 277-278° C.
Reaction SMILES: [S:1]1[C:5]2[CH:6]([C:10]([O:12]C)=[O:11])[CH2:7][CH2:8][CH2:9][C:4]=2[N:3]=[CH:2]1.O[Li].O>C1COCC1.CO.O>[S:1]1[C:5]2[CH:6]([C:10]([OH:12])=[O:11])[CH2:7][CH2:8][CH2:9][C:4]=2[N:3]=[CH:2]1
Reactant: COC(=O)C1CCCc2ncsc21
Agent: [Li]O
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)C1CCCc2ncsc21
Temperature: 25 °C
Reaction time: 1.25 h

Procedure:
A mixture of methyl 4,5,6,7-tetrahydrobenzo[d]thiazole-7-carboxylate (1.22 g, 6.11 mmol) and LiOH.H2O (0.39 g, 9.17 mmol) in THF/MeOH/H2O (60 mL, 3:1:1) was stirred at RT for 75 min. The mixture was acidified to pH=3 and extracted with DCM. The comb. org. layers were dried over MgSO4 and conc. in vacuo to provide a yellow solid.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]3=[N:13][CH:14]=[N:15][C:16]([NH2:17])=[C:11]3[CH:10]=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[S:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[C:23](O)=[O:24].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C=O)C.CO>[NH2:17][C:16]1[N:15]=[CH:14][N:13]=[C:12]2[N:8]([C:4]3[CH:3]=[C:2]([NH:1][C:23]([C:19]4[S:18][CH:22]=[CH:21][CH:20]=4)=[O:24])[CH:7]=[CH:6][CH:5]=3)[N:9]=[CH:10][C:11]=12
Reactant: Nc1cccc(-n2ncc3c(N)ncnc32)c1
Reactant: O=C(O)c1cccs1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CO
Solvent: CN(C)C=O
Product: Nc1ncnc2c1cnn2-c1cccc(NC(=O)c2cccs2)c1
Reaction time: 0.17 h
Yield: 12.5 %

Procedure:
Title compound 11B, 1-(3-amino-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine (39 mg, 1.1 eq, 0.17 mmol) was added to a solution 2-thiophenecarboxylic acid (20 mg, 1.0 eq, 0.16 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (27 mg, 1.1 eq, 0.17 mmol), 1-hydroxybenzotriazole (21 mg, 1.0 eq, 0.16 mmol) in DMF (1 ml) which had been stirred for 10 minutes under an inert atmosphere. The reaction was stirred at room temperature for 17 hours, after which methanol (1 ml) was added, and the solvents were removed in vacuo. The residue was then triturated with methanol and the resultant solid was isolated by filtration to yield the title compound as a pale yellow solid (6 mg, 0.02 mmol, 11%). LCMS: [M+H]+=337, Rt=1.60 min, 100% purity.
Reaction SMILES: [CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][CH:3]1[CH2:7][NH2:8].[CH3:9][NH:10][S:11]([C:14]1[CH:15]=[C:16]([C:24](Cl)=[O:25])[C:17]2[O:22][CH2:21][CH2:20][O:19][C:18]=2[CH:23]=1)(=[O:13])=[O:12].O>C(Cl)(Cl)Cl>[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][CH:3]1[CH2:7][NH:8][C:24]([C:16]1[C:17]2[O:22][CH2:21][CH2:20][O:19][C:18]=2[CH:23]=[C:14]([S:11](=[O:13])(=[O:12])[NH:10][CH3:9])[CH:15]=1)=[O:25]
Reactant: CNS(=O)(=O)c1cc2c(c(C(=O)Cl)c1)OCCO2
Reactant: CN1CCCC1CN
Solvent: ClC(Cl)Cl
Solvent: O
Product: CNS(=O)(=O)c1cc2c(c(C(=O)NCC3CCCN3C)c1)OCCO2
Yield: 78.5 %

Procedure:
61 g of dextrorotatory 1-methyl-2-aminomethylpyrrolidine, 465 ccm of chloroform and, in portions, 155 g of 7-methylsulfamoyl-1,4-benzodioxane-5-carbonyl chloride, with the temperature being maintained at 5°-10° C., were introduced into a balloon flask provided with an agitator and a thermometer. After agitation of the mixture and the addition of 1,850 cm3 of water, chloroform was distilled and the remaining solution was filtered. The base was precipitated by the addition of 65 cm3 of 20% ammonia. The crystals formed were dried off, washed and dried. 154 g of dextrorotatory-N-(1-methyl-2-pyrrolidylmethyl)-7-methylsulfamoyl-1,4-benzodioxane-5-carboxamide was produced (M.P.: 187°-188° C.; yield: 78.5%).
Reaction SMILES: [H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[N:4]1.[F:8][C:9]1[CH:10]=[C:11]([C:16]2[CH2:20][CH:19]([CH2:21][N:22]3[CH:26]=[CH:25][N:24]=[N:23]3)[O:18][N:17]=2)[CH:12]=[CH:13][C:14]=1F>CN(C)C=O>[F:8][C:9]1[CH:10]=[C:11]([C:16]2[CH2:20][CH:19]([CH2:21][N:22]3[CH:26]=[CH:25][N:24]=[N:23]3)[O:18][N:17]=2)[CH:12]=[CH:13][C:14]=1[N:3]1[CH:7]=[CH:6][N:5]=[N:4]1
Reactant: Fc1ccc(C2=NOC(Cn3ccnn3)C2)cc1F
Reactant: c1c[nH]nn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Fc1cc(C2=NOC(Cn3ccnn3)C2)ccc1-n1ccnn1
Temperature: 25 °C
Reaction time: 16 h
Yield: 3.8 %

Procedure:
A slurry of sodium hydride (60% in oil, 44 mg, 1.1 mM) in anhydrous N,N-dimethylformamide (1 ml) was stirred under an atmosphere of nitrogen and treated dropwise with a solution of 1,2,3-triazole (76 mg, 1.1 mM) in anhydrous N,N-dimethylformamide (1 ml) at 0°. The mixture was allowed to warm to ambient temperature over 20 minutes, then a solution of (5RS)-3-(3,4-difluorophenyl)-5-(1,2,3-triazol-1-yl-methyl)-4,5-dihydroisoxazole (264 mg, 1 mM) in anhydrous N,N-dimethylformamide (2 ml) added, and the mixture stirred at 70° for 16 hours. After cooling, the mixture was partitioned between aqueous sodium bicarbonate solution (40 ml) and ethyl acetate (40 ml), and the organic extract washed with water (40 ml) and brine (40 ml). After drying (magnesium sulfate) and evaporation, the crude product was chromatographed on a 20 g silica Mega Bond Elut® column, eluting with ethyl acetate. Relevant fractions were combined to give the desired product (12 mg).
Reaction SMILES: [C:1]([CH2:3][CH:4]([OH:16])[CH2:5][CH:6]([OH:15])[CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])#[N:2].[C:17]12(CS(O)(=O)=O)C(C)(C)C(C[CH2:23]1)C[C:18]2=O>COC(OC)(C)C>[C:1]([CH2:3][C@H:4]1[O:16][C:17]([CH3:23])([CH3:18])[O:15][C@@H:6]([CH2:7][C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[CH2:5]1)#[N:2]
Reactant: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Reactant: CC(C)(C)OC(=O)CC(O)CC(O)CC#N
Solvent: COC(C)(C)OC
Product: CC(C)(C)OC(=O)C[C@H]1C[C@@H](CC#N)OC(C)(C)O1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Crude [R-(R*,R*)]-1,1-dimethylethyl 6-cyano-3,5-dihydroxyhexanoate, 15 g (61 mol), is dissolved in 150 mL of 2,2-dimethoxypropane, camphorsulfonic acid is added, and the solution is stirred for 18 hours at room temperature. Concentration and flash chromatography after concentration in vacuo provides 11.8 g of (4R-cis)-1,1-dimethyethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate as an off-white solid, mp 64.7°-68° C. with acceptable IR, NMR, C-NMR and analysis.
Reaction SMILES: [O:1]=[O+][O-].[CH3:4][C:5]1([CH3:21])[CH2:10][C:9]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)([CH2:11][CH:12]=C)[CH2:8][CH2:7][O:6]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH3:4][C:5]1([CH3:21])[CH2:10][C:9]([CH2:11][CH:12]=[O:1])([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[CH2:8][CH2:7][O:6]1
Reactant: O=[O+][O-]
Reactant: C=CCC1(c2ccc(C)cc2)CCOC(C)(C)C1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: Cc1ccc(C2(CC=O)CCOC(C)(C)C2)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 52 %

Procedure:
O3 gas was passed through a solution of 2,2-dimethyl-4-(4-methylphenyl)-4-(prop-2-en-1-yl)oxane (1.21 g, 5 mmol) in CH2Cl2 (50 ml) at −78° C. until the solution turned light blue (about 5 min). After additional 5 minutes, the reaction mix was purged with oxygen gas for 15 min before adding triphenylphosphine (2.62 g, 10 mmol). The reaction was stirred at rt for 4 h and concentrated. Purified by normal phase SiO2 chromatography (10 to 60% EtOAc/hexanes) to give 2-[2,2-dimethyl-4-(4-methylphenyl)oxan-4-yl]acetaldehyde as a colorless oil (641 mg, 52%).
Reaction SMILES: [Br:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)=[O:4].[C:17]([NH2:21])([CH3:20])([CH3:19])[CH3:18]>C(#N)C>[BrH:1].[C:11]1([C:8]2[CH:9]=[CH:10][C:5]([C:3](=[O:4])[CH2:2][NH:21][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:6][CH:7]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=C(CBr)c1ccc(-c2ccccc2)cc1
Reactant: CC(C)(C)N
Solvent: CC#N
Product: Br
Product: CC(C)(C)NCC(=O)c1ccc(-c2ccccc2)cc1

Procedure:
This Example was carried out in a similar manner to Example 2. 2-Bromo-4'-phenylacetophenone (25.0 g) in acetonitrile (150 ml) was reacted with tert-butylamine (28.4 ml) to give 4'-phenyl-2-(tert-butylamino)acetophenone hydrobromide (5.31 g) m.p. 234-237° C. (with decomposition). This compound was reacted with malononitrile (1.7 g) and potassium hydroxide (3.0 g) in water (4 ml) in methanol (100 ml) under nitrogen to give 2-amino-4-(4-biphenylyl)-3-cyano-1-(tert-butyl)pyrrole (3.75 g) which was suspended in formamide (200 ml) saturated with ammonia and then the mixture was heated at 200-205° C. for two hours whilst ammonia was being passed through the mixture. After cooling the mixture was added to ice-water (600 g) under nitrogen and the solid collected by filtration, purified by flash column chromatography on silica using ethyl acetate/triethylamine (19:1) as the mobile phase to give 5-(4-biphenylyl)-7-tert-butyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine, m.p. 212-214° C.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[N+:9]([C:12]1[CH:17]=[CH:16][C:15]([S:18](Cl)(=[O:20])=[O:19])=[CH:14][CH:13]=1)([O-:11])=[O:10].C(O)(=O)C>N1C=CC=CC=1>[N+:9]([C:12]1[CH:13]=[CH:14][C:15]([S:18]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=2)(=[O:20])=[O:19])=[CH:16][CH:17]=1)([O-:11])=[O:10]
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1ccc(O)cc1
Solvent: CC(=O)O
Solvent: c1ccncc1
Product: O=[N+]([O-])c1ccc(S(=O)(=O)Nc2ccc(O)cc2)cc1
Temperature: 0 °C
Yield: 72 %

Procedure:
A mixture of 4-aminophenol (27 g, 0.25 mole) and 4-nitrobenzenesulfonyl chloride (55 g, 0.25 mole) in pyridine (500 ml) was heated under reflux for 4 hours. The reaction mixture was poured in ice water and acidified with acetic acid. The crude product weighed 86 g. Recrystallization from CH3NO2 provided 53 g (73%) of material used in Part B; m.p. 197°-198°.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10]([C:18]([OH:20])=O)=[N:11][NH:12][C:13]=1[C:14]([O:16][CH3:17])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH:37]([OH:41])[CH2:38][NH:39][CH3:40])[CH:32]=1.C(N(CC)CC)C.C(Cl)CCl>CN(C=O)C>[CH3:40][N:39]([CH2:38][CH:37]([OH:41])[C:33]1[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=1)[C:18]([C:10]1[NH:11][N:12]=[C:13]([C:14]([O:16][CH3:17])=[O:15])[C:9]=1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:20]
Reactant: CNCC(O)c1cccnc1
Reactant: COC(=O)c1[nH]nc(C(=O)O)c1OCc1ccccc1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COC(=O)c1n[nH]c(C(=O)N(C)CC(O)c2cccnc2)c1OCc1ccccc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of methyl 4-benzyloxy-3-carboxy-1H-pyrazole-5-carboxylate (2.0 g, 7.24 mmol) in DMF (30 mL) were added HOBT (1.17 g, 8.69 mmol), 1-(3-pyridyl)-2-methylaminoethanol (1.21 g, 7.96 mmol; prepared by the methods of Tsushima, S., et al., EP 278621 and Cudahy, M. M., et al., WO 2003059911), triethylamine (0.88 g, 8.69 mmol), and EDC (1.67 g, 8.69 mmol). The reaction mixture was stirred at ambient temperature for 18 hours. The DMF was removed in vacuo and the residue was purified by prep HPLC (Waters prep LC 4000 System using a Waters Nova Pak column (3 100×40 mm I.D. cartridges, C18, 6 μM pore size) eluting with 95-5% water (0.10% TFA)/acetonitrile (0.10% TFA) at 60 mL/minute). Appropriate fractions were combined and the solvent was removed under reduced pressure to give a yellow solid. The free base of the product was obtained by partitioning between aqueous NaHCO3 and ethyl acetate. The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo to give a gum. ES MS (M+1)=277.
Reaction SMILES: [CH2:1]([O:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9](I)=[CH:8][CH:7]=1)[CH3:2].[F:13][C:14]([F:22])([F:21])[C:15]([F:20])([F:19])C([O-])=O.[Na+].CN(C=O)C>[Cu]I.C1(C)C=CC=CC=1>[CH2:1]([O:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:15]([F:20])([F:19])[C:14]([F:22])([F:21])[F:13])=[CH:8][CH:7]=1)[CH3:2]
Reactant: O=C([O-])C(F)(F)C(F)(F)F
Reactant: CCOCOc1ccc(I)cc1
Agent: [Cu]I
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: CCOCOc1ccc(C(F)(F)C(F)(F)F)cc1
Temperature: 145 °C

Procedure:
A mixture of 7.5 g of crude product of 1-ethoxymethoxy-4-iodobenzene, 10.0 g of sodium pentafluoropropionate salt, 10.27 g of copper (I) iodide, 120 ml of DMF and 45 ml of toluene was stirred while heating at 140 to 150° C. for one hour to remove about 40 ml of toluene. The reaction mixture was heated to reflux at 160 to 170° C. for further five hours, and then cooled to room temperature and poured into ice water. To the reaction mixture, 200 ml of diethyl ether was added. The reaction mixture was filtered through Celite™. The filtrate was extracted with diethyl ether. The combined organic layers were washed with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 5.45 g of 1-ethoxymethoxy-4-pentafluoroethyl benzene.
Reaction SMILES: [CH2:1]([N:8]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C@@H:9]([CH2:20][CH2:21][CH3:22])[C:10]([O:12]CC1C=CC=CC=1)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].Cl>CO.O>[CH2:23]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@@H:9]([CH2:20][CH2:21][CH3:22])[C:10]([OH:12])=[O:11])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: CCC[C@@H](C(=O)OCc1ccccc1)N(Cc1ccccc1)Cc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CCC[C@@H](C(=O)O)N(Cc1ccccc1)Cc1ccccc1
Temperature: 90 °C
Yield: 66.3 %

Procedure:
The crude (S)-benzyl 2-(dibenzylamino)pentanoate (3) (2.2 Kg) was dissolved in methanol (5.5 L). A previously prepared, cold (0-5° C.) solution of sodium hydroxide (568 g; 14.2 mol) in water (6 L) was added to the solution of (3), and the resulting mixture heated at 90° C. for 20 hours. The reaction mixture was then allowed to cool to ambient temperature, and the methanol evaporated under reduced pressure. The residue was diluted with water (25 L), and extracted with methyl t-butyl ether/hexane (1:1; 2×5 L) to remove the benzyl alcohol formed in the hydrolysis. The basic aqueous layer was acidified to pH 2 with 6M aqueous hydrochloric acid (4 L), then extracted with ethyl acetate (2×8 L). The combined organic extracts were dried over sodium sulfate and the solvent removed under reduced pressure, to afford a semi solid, which was washed with hexanes (8 L) to provide 1.12 Kg of (S)-2-(dibenzylamino)pentanoic acid, a compound of formula (4), as a white solid.
Reaction SMILES: [OH-].[Na+:2].[NH:3]1[C:7]([C:8]2[CH:9]=[C:10]([CH:17]=[CH:18][CH:19]=2)[NH:11][C:12](=[O:16])[C:13]([OH:15])=[O:14])=[N:6][N:5]=[N:4]1.C(OCC)C>CO>[NH:6]1[C:7]([C:8]2[CH:9]=[C:10]([CH:17]=[CH:18][CH:19]=2)[NH:11][C:12](=[O:16])[C:13]([O-:15])=[O:14])=[N:3][N:4]=[N:5]1.[Na+:2].[Na+:2].[NH:6]1[C:7]([C:8]2[CH:9]=[C:10]([CH:17]=[CH:18][CH:19]=2)[NH:11][C:12](=[O:16])[C:13]([O-:15])=[O:14])=[N:3][N:4]=[N:5]1
Reactant: O=C(O)C(=O)Nc1cccc(-c2nnn[nH]2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: CO
Product: O=C([O-])C(=O)Nc1cccc(-c2nnn[nH]2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.1 %

Procedure:
Sodium hydroxide (1.72 g; 43 mmol) was dissolved in methanol (100 ml), 3-(1H-tetrazol-5-yl)oxanilic acid (5 g; 21.5 mmol) was added thereto and the mixture was stirred for 1 hour at room temperature. The reaction solution was poured into 300 ml of ethyl ether at room temperature with stirring, the precipitated crystals were filtered off and were dried at 40° C. in vacuo in the presence of phosphorous pentoxide to obtain 5 g (yield 85%) of disodium 3-(1H-tetrazol-5-yl)oxanilate. Decomposition point: not less than 300° C.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11][CH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[NH:23][C:22](=[O:27])[CH2:21][CH2:20]2.[OH:28]O>>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11]([CH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[NH:23][C:22](=[O:27])[CH2:21][CH2:20]2)=[O:28]
Reactant: OO
Reactant: O=C1CCc2cc(OCCCCSc3ccc4ccccc4c3)ccc2N1
Product: O=C1CCc2cc(OCCCCS(=O)c3ccc4ccccc4c3)ccc2N1

Procedure:
Prepared analogous to Example 2 from 6-[4-(2-naphthyl-mercapto)-butoxy]-3,4-dihydro-carbostyril and hydrogen peroxide.
Reaction SMILES: CN1C=C(CN(C)C(C2N(C3C=CC(F)=CC=3)C(S)=NC=2)=O)C(C)=N1.[F:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[C:37]([C:38]([O:40]CC)=[O:39])=[CH:36][N:35]=[C:34]2[CH2:43][CH2:44][C:45]2[C:50]([F:51])=[CH:49][CH:48]=[C:47]([F:52])[C:46]=2[F:53])=[CH:29][CH:28]=1.[OH-].[Li+].C1COCC1>O.CO>[F:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[C:37]([C:38]([OH:40])=[O:39])=[CH:36][N:35]=[C:34]2[CH2:43][CH2:44][C:45]2[C:50]([F:51])=[CH:49][CH:48]=[C:47]([F:52])[C:46]=2[F:53])=[CH:29][CH:28]=1
Reactant: CCOC(=O)c1cnc(CCc2c(F)ccc(F)c2F)n1-c1ccc(F)cc1
Agent: Cc1nn(C)cc1CN(C)C(=O)c1cnc(S)n1-c1ccc(F)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)c1cnc(CCc2c(F)ccc(F)c2F)n1-c1ccc(F)cc1

Procedure:
1-(4-fluorophenyl)-2-(2,3,6-trifluorophenethyl)-1H-imidazole-5-carboxylic acid (19) was prepared in a similar manner as that described for the synthesis of compound 7 using ethyl 1-(4-fluorophenyl)-2-(2,3,6-trifluorophenethyl)-1H-imidazole-5-carboxylate (18) (50 mg, 0.13 mmol), lithium hydroxide (12 mg, 0.51 mmol), THF (0.2 mL), methanol (0.4 mL), and water (0.8 mL).
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[Cl:5][CH2:6][C:7](Cl)=[O:8].[CH2:10]([C:12]1[CH:13]=[CH:14][C:15]([O:26][CH3:27])=[C:16]([C:18]2[CH:23]=[CH:22][C:21]([O:24]C)=[CH:20][CH:19]=2)[CH:17]=1)[CH3:11]>ClCCCl>[Cl:5][CH2:6][C:7]([C:20]1[CH:19]=[C:18]([C:16]2[CH:17]=[C:12]([CH2:10][CH3:11])[CH:13]=[CH:14][C:15]=2[O:26][CH3:27])[CH:23]=[CH:22][C:21]=1[OH:24])=[O:8]
Reactant: O=C(Cl)CCl
Reactant: CCc1ccc(OC)c(-c2ccc(OC)cc2)c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCCl
Product: CCc1ccc(OC)c(-c2ccc(O)c(C(=O)CCl)c2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture was prepared by suspending 25 g of aluminium chloride into 100 ml of 1,2-dichloroethane. The mixture, wherein 5 ml chloroacetyl chloride was added, was stirred for 1 hour at room temperature, followed by dropwise addition of 5-ethyl-2,4'-dimethoxy-biphenyl, wherein 10 g of 1.2-dichloroethane was dropwise and stirred overnight at room temperature. The reaction mixture was transferred into ice water to extract with dichloroethane. The extract was washed with saturated salt water, dried with sodium sulfate and concentrated. The concentrate was purified by a silica gel column chromatography (10:1, n-hexane:ethyl acetate) and recrystallized from chloroform/n-hexane to yield 2.5 g of light yellow and powdered 2-chloroacetyl-4-(5-ethyl-2-methoxyphenyl)phenol having a m.p. of 67.0°-68.0° C. Then, the fraction which was eluted with n-hexane/ethyl acetate: 3/1, was concentrated. The concentrate was recrystallized from chloroform/n-hexane to yield 1.5 g of white powder 3,3-bischloroacetyl-5-ethyl-2,4'-biphenyldiol having a m.p. of 154.0°-155.5° C.
Reaction SMILES: [C:1](=[O:12])([S:9][CH2:10][CH3:11])[O:2][O:3][CH:4](Cl)[CH2:5][CH2:6][CH3:7].[CH:13]1([C:18]([OH:20])=[O:19])[CH2:17][CH2:16][CH2:15][CH2:14]1>>[C:1](=[O:12])([S:9][CH2:10][CH3:11])[O:2][O:3][CH:4]([O:20][C:18]([CH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:19])[CH2:5][CH2:6][CH3:7]
Reactant: O=C(O)C1CCCC1
Reactant: CCCC(Cl)OOC(=O)SCC
Product: CCCC(OOC(=O)SCC)OC(=O)C1CCCC1
Temperature: 75 °C
Reaction time: 120 h
Yield: 82.5 %

Procedure:
A mixture of (66) (1.33 g, 6.76 mmol) and cyclopentancarboxylic acid (1.30 g, 10.1 mmol) was stirred at 75° C. for five days. The reaction was then cooled to room temperature and partitioned between water and ether. The ether layer was washed with brine, dried over anhydrous Na2SO4. Filtration then removal of the solvent by rotary evaporation gave the title thiocarbonate (67) (1.62 g, 86%). 1H NMR (CDCl3, 400 MHz): δ 0.95 (t, 3H), 1.20-1.85 (m, 15H), 2.68 (m, 1H), 2.82 (m, 2H). 6.84 (t, 1H).
Reaction SMILES: C(N(CC)CC)C.O=O.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([C@:17]2([O:26][C@H:25]([CH2:27][OH:28])[C@@H:23]([OH:24])[C@H:21]([OH:22])[C@H:19]2[OH:20])[OH:18])=[CH:13][C:12]=1[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]#[CH:37])=[CH:32][CH:31]=1.Br[C:39]1[CH:40]=[N:41][CH:42]=[N:43][CH:44]=1>CN(C)C=O.[Cu](I)I.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>[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([C@:17]2([O:26][C@H:25]([CH2:27][OH:28])[C@@H:23]([OH:24])[C@H:21]([OH:22])[C@H:19]2[OH:20])[OH:18])=[CH:13][C:12]=1[CH2:29][C:30]1[CH:31]=[CH:32][C:33]([C:36]#[C:37][C:39]2[CH:40]=[N:41][CH:42]=[N:43][CH:44]=2)=[CH:34][CH:35]=1
Reactant: C#Cc1ccc(Cc2cc([C@@]3(O)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)ccc2Cl)cc1
Reactant: Brc1cncnc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: I[Cu]I
Agent: O=O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: OC[C@H]1O[C@](O)(c2ccc(Cl)c(Cc3ccc(C#Cc4cncnc4)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O
Temperature: 60 °C
Reaction time: 16 h

Procedure:
37 mg copper iodide, 67 mg bis-(triphenylphosphine)-palladium dichloride and 0.46 mL triethylamine are added to an oxygen-free solution of 0.35 g 1-chloro-4-(β-D-glucopyranos-1-yl)-2-(4-ethynyl-benzyl)-benzene and 0.2 g 5-bromo-pyrimidine in 1 mL dimethylformamide. The solution is stirred under argon atmosphere at 60° C. for 16 h. The reaction mixture is filtered through Celite and evaporated down. The residue is chromatographed on silica gel (dichloromethane/methanol 1:0→9:1).