Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10]([C:21]3[CH:26]=[CH:25][C:24](C)=[CH:23][CH:22]=3)=[C:11]([C:13]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)=[O:14])[N:12]=2)=[CH:4][CH:3]=1.[C:28](Cl)(=[O:30])[CH3:29].N1C=CC=C[CH:33]=1>>[C:28]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[CH3:33])=[C:11]([C:13]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)=[O:14])[N:12]=2)=[CH:4][CH:3]=1)(=[O:30])[CH3:29]
Reactant: c1ccncc1
Reactant: CC(=O)Cl
Reactant: Cc1ccc(-c2[nH]c(-c3ccc(N)cc3)nc2C(=O)Nc2nccs2)cc1
Product: CC(=O)Nc1ccc(-c2nc(C(=O)Nc3nccs3)c(-c3ccccc3C)[nH]2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
2-(4-Aminophenyl)-5-(4-methylphenyl)-N-(2-thiazolyl)-imidazole-4-carboxamide (0.30 g) obtained in Example 21 was dissolved in pyridine (20 ml) and acetyl chloride (0.8 ml) was added dropwise under ice-cooling. The mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated to give white crystals, which were recrystallized from ethyl acetate to give 2-(4-acetamidophenyl)-5-(methylphenyl)-N-(2-thiazolyl)imidazole-4-carboxamide (0.17 g), melting point 269-271° C.
Reaction SMILES: [CH2:1]([O:8][CH2:9][C:10]([CH3:14])([OH:13])[CH2:11][OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:17](Cl)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(Cl)Cl.CCOCC>CN(C)C=O>[CH2:1]([O:8][CH2:9][C:10]([CH3:14])([OH:13])[CH2:11][O:12][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: ClCc1ccccc1
Reactant: CC(O)(CO)COCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(O)(COCc1ccccc1)COCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
1 -Benzyloxymethyl-1-methyl-ethane-1, 2-diol (5g) in dimethylformamide (25 ml) was treated with sodium hydride (0.65g), the reaction mixture was stirred at ambient temperature for 1 h. then at 90° C for 15 min. The reaction mixture was cooled and benzyl chloride (3.3g) added; it was stirred for 4 h. at ambient temperature. The solvent was evaporated and the product isolated by chromatography on silica gel using methylene chloride/ether (9/1) to give the desired product as a colourless oil. The 1,3-configuration was confirmed by n.m.r. which showed the methylene groups of the carbon backbone to be equivalent, hence, establishing the symmetry of the molecule.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[O:10][C:11]([CH:26]([CH3:28])[CH3:27])=[C:12]([CH2:14][CH2:15][C:16]([C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[C:20]([CH3:25])[CH:19]=2)=[O:17])[N:13]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38]>CC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[O:10][C:11]([CH:26]([CH3:28])[CH3:27])=[C:12]([CH2:14][CH2:15][C:16]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])=[C:20]([CH3:25])[CH:19]=2)=[O:17])[N:13]=1
Reactant: Cc1cc(C(=O)CCc2nc(-c3ccc(Cl)cc3Cl)oc2C(C)C)ccc1O
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)COc1ccc(C(=O)CCc2nc(-c3ccc(Cl)cc3Cl)oc2C(C)C)cc1C
Yield: 92.8 %

Procedure:
The synthetic intermediate of Example 1, namely 3-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]-1-(3-methyl-4-hydroxyphenyl)propan-1-one (105 mg, 0.25 mmol) and potassium carbonate (103 mg, 0.75 mmol) were suspended in acetone (3 mL). Ethyl bromoacetate (0.08 mL, 0.75 mmol) was added to the suspension while cooling with ice. The suspension was allowed to room temperature, and refluxed while heating for 6 hours. Insolubles were filtered, and washed with acetone. Subsequently, the solvent was distilled off. The residue was purified by column chromatography on silica gel with hexane/ethyl acetate (7/1-4/1) to give the subject compound (117 mg) as colorless oil (yield 92%)
Reaction SMILES: F[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.CCN(CC)CC.[NH2:18][C@H:19]([C:21]([OH:23])=[O:22])[CH3:20]>CO>[N+:8]([C:7]1[C:2]([NH:18][CH:19]([CH3:20])[C:21]([OH:23])=[O:22])=[N:3][CH:4]=[CH:5][CH:6]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1cccnc1F
Reactant: C[C@H](N)C(=O)O
Solvent: CO
Solvent: CCN(CC)CC
Product: CC(Nc1ncccc1[N+](=O)[O-])C(=O)O
Temperature: 25 °C
Yield: 43.7 %

Procedure:
A mixture of 2-fluoro-3-nitro-pyridine (12 g), Et3N (30 mL), and racemic alanine (11.87 g) was refluxed in methanol (200 mL) overnight. The mixture was cooled to ambient temperature and the filtrate was concentrated in vacuo. The residue was partitioned between DCM and water. The organic layer was dried over Na2CO3, filtered, and concentrated in vacuo to afford 2-(3-nitro-pyridin-2-ylamino)-propionic acid (7.8 g). This material was dissolved in AcOH (50 mL) and iron (8.2 g) was added. The mixture was refluxed for 1.5 h. After cooling to ambient temperature, the mixture was filtered, and the filtrate was concentrated in vacuo. The residue was washed with water and dried to afford 3-methyl-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (1.4 g). This material was mixed with 5% aq NaOH (92 mL) and water (18 mL) before 30% aq hydrogen peroxide (9.2 mL) was added. The mixture was stirred at 60° C. for 10 h. After cooling to ambient temperature the pH was adjusted to neutral to precipitate 3-methyl-1H-pyrido[2,3-b]pyrazin-2-one (1.2 g). This material was dissolved in DMF (10 mL) and treated with PyBroP (4.6 g) and DIPEA (1.6 mL) at ambient temperature of 16 h. The precipitated white solid was filtered off, washed with ethanol and dried to afford 2-(benzotriazol-1-yloxy)-3-methyl-pyrido[2,3-b]pyrazine (0.4 g). This material (0.4 g) and hydrazine hydrate (0.5 mL) were refluxed in ethanol (5 mL) for 10 min. After cooling to ambient temperature, the precipitated white solid was filtered off, washed with ethanol and dried to afford give IIa (0.2 g) sufficiently pure for the next step.
Reaction SMILES: CON(C)[C:4]([C:6]1[O:7][C:8]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][C:9]=2[C:10]=1[CH3:11])=[O:5].[H-].[Al+3].[Li+].[H-].[H-].[H-].O>O1CCCC1>[CH3:11][C:10]1[C:9]2[CH:12]=[C:13]([CH3:16])[CH:14]=[CH:15][C:8]=2[O:7][C:6]=1[CH:4]=[O:5]
Reactant: CON(C)C(=O)c1oc2ccc(C)cc2c1C
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccc2oc(C=O)c(C)c2c1
Reaction time: 2 h
Yield: 73.7 %

Procedure:
To a solution (50 mL) of N-methoxy-N,3,5-trimethyl-1-benzofuran-2-carboxamide (3.78 g) synthesized above in tetrahydrofuran was added lithium aluminum hydride (307 mg) at −78° C., and the mixture was stirred for 2 hr. Water (350 μL) was added to quench the reaction, 1N aqueous sodium hydroxide solution (700 μL) was added, and the mixture was stirred at room temperature for 1 hr. The resulting insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was washed with hexane to give the title object compound (2.08 g, 74%) as a yellow solid.
Reaction SMILES: [CH3:1][O:2][CH:3]([O:6][CH3:7])[CH:4]=O.[CH3:8][C:9]([CH3:14])([CH3:13])[C@H:10]([NH2:12])[CH3:11]>CO.[Pd]>[CH3:1][O:2][CH:3]([O:6][CH3:7])[CH2:4][NH:12][C@@H:10]([C:9]([CH3:14])([CH3:13])[CH3:8])[CH3:11]
Reactant: C[C@@H](N)C(C)(C)C
Reactant: COC(C=O)OC
Agent: [Pd]
Solvent: CO
Product: COC(CN[C@H](C)C(C)(C)C)OC
Reaction time: 2 h

Procedure:
2,2-Dimethoxyacetaldehyde (7.54 mL) was added to a solution of (R)-3,3-dimethylbutan-2-amine (5.06 g) in methanol (20 mL) and the mixture stirred for 2 h. A slurry of palladium on carbon (10%, 200 mg) in methanol (5 mL) was added and the mixture hydrogenated at 5 bar for 66 h. The mixture was then filtered and concentrated in vacuo to afford (R)- N-(2,2-dimethoxyethyl)-3,3-dimethylbutan-2-amine (8.78 g) as an oil. 1H NMR (400 MHz, CDCl3) δ 4.47 (t, J=5.6 Hz, 1H), 3.38 (s, 3H), 3.37 (s, 3H), 2.86 (dd, J=12.2, 5.5 Hz, 1H), 2.58 (dd, J=12.1, 5.9 Hz, 1H), 2.23 (q, J=6.4 Hz, 1H), 0.97 (d, J=6.4 Hz, 3H), 0.89 (s, 9H)
Reaction SMILES: [OH:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:9](=[O:13])[CH2:10][O:11][CH3:12])=[C:4]([CH3:14])[CH:3]=1.Br[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1/[C:23](=[CH:28]\[O:29][CH3:30])/[C:24]([O:26][CH3:27])=[O:25].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH3:30][O:29]/[CH:28]=[C:23](\[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[CH2:16][O:1][C:2]1[CH:3]=[C:4]([CH3:14])[C:5]([C:9](=[O:13])[CH2:10][O:11][CH3:12])=[CH:6][C:7]=1[CH3:8])/[C:24]([O:26][CH3:27])=[O:25]
Reactant: COCC(=O)c1cc(C)c(O)cc1C
Reactant: CO/C=C(/C(=O)OC)c1ccccc1CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CO/C=C(/C(=O)OC)c1ccccc1COc1cc(C)c(C(=O)COC)cc1C
Yield: 76.1 %

Procedure:
In 30 mL of acetonitrile (CH3CN), 0.3 g (1.55 mmol) of 1-(4-hydroxy-2,5-dimethylphenyl)-2-methoxyethanone obtained in Step 1 was reacted for 4 hours with 0.44 g (1.55 mmol) of (E)-methyl 2-(2-(bromomethyl)phenyl)-3-methoxyacrylate in the presence of 20.45 g (2.1 eq) of potassium carbonate under reflux. After completion of the reaction, the solvent was removed at a reduced pressure and the residue was stirred in water (30 mL) and extracted twice with 30 mL of dichloromethane. The organic layer was dried over anhydrous magnesium sulfate and concentrated in a vacuum, followed by purification with silica gel to afford 0.47 g of (E)-methyl 3-methoxy-2-(2-((4-(2-methoxyacetyl)-2,5-dimethylphenoxy)methyl)phenyl)acrylate as a white solid (yield: 76%).
Reaction SMILES: [CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:36])[CH:15]([CH2:19][C:20]1[C:25]([CH3:26])=[CH:24][C:23]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:22][C:21]=1[CH3:35])[CH2:16][CH:17]=C)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC([OH:41])(C)C.I([O-])(=O)(=O)=O.[Na+]>C1COCC1.O.O=[Os](=O)(=O)=O>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:36])[C@H:15]([CH2:19][C:20]1[C:21]([CH3:35])=[CH:22][C:23]([O:27][CH2:28][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)=[CH:24][C:25]=1[CH3:26])[CH2:16][CH:17]=[O:41])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C=CCC(Cc1c(C)cc(OCc2ccccc2)cc1C)C(=O)N1C(=O)OC[C@H]1Cc1ccccc1
Reactant: CC(C)(C)O
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: C1CCOC1
Solvent: O
Product: Cc1cc(OCc2ccccc2)cc(C)c1C[C@H](CC=O)C(=O)N1C(=O)OC[C@H]1Cc1ccccc1
Yield: 418.3 %

Procedure:
Treat a solution of (R)-4-Benzyl-3-[2-(4-benzyloxy-2,6-dimethyl-benzyl)-pent-4-enoyl]-oxazolidin-2-one (7.5 g, 16 mmol) in THF (120 mL) and water (40 mL) with 2.5% OsO4 in tBuOH (16 g, 1.6 mmol). Add Sodium periodate (10 g, 47 mmol) to the solution and stir the reaction for 3 hr at room temperature. Quench the reaction with water and extract with EtOAc. Wash the organic with 1N sodium thiosulfate and brine. Separate the organic, dry over MgSO4, filter, and remove the solvent. Purify the crude by silica gel column chromatography using Hexanes:EtOAc to elute the pure product. Remove the solvent to afford 3.25 g (43%) of desired product. MS (m/e): 486 (M+1).
Reaction SMILES: [O:1]=[C:2]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[H-].[Na+].I[CH3:18]>O1CCCC1>[CH3:18][CH:9]([C:2](=[O:1])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: CI
Reactant: CCOC(=O)CC(=O)CC(=O)OCC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)CC(=O)C(C)C(=O)OCC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 36.3 %

Procedure:
To a solution of diethyl 3-oxopentanedioate (23.2 g, 114.8 mmol) in tetrahydrofuran (100 mL) was added sodium hydride (60%, 4.8 g, 120.5 mmol) at 0° C., and the reaction mixture was stirred at RT for 30 mins, followed by the addition of iodomethane (7.15 ml, 114.8 mmol). The reaction mixture was stirred at RT for 48 h, quenched with water (500 mL) and extracted with ethyl acetate (500 mL×3). The organic layers were separated, combined, washed with water (200 mL) and brine (200 mL), dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel column (petroleum ether: ethyl acetate=20:1) to get the title compound as a colorless oil (9 g, 36%). MS (ES+) C10H16O5 requires: 216. found: 217 [M+H]+.
Reaction SMILES: [C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4])[OH:2].C(N(CC)CC)C.Cl[C:17](=[C:22]([Cl:27])[C:23]([F:26])([F:25])[F:24])[C:18]([F:21])([F:20])[F:19]>C(#N)C>[Cl:27][CH:22]([C:17]1([C:18]([F:19])([F:20])[F:21])[O:4][C:3]2[CH:5]=[CH:6][CH:7]=[CH:8][C:1]=2[O:2]1)[C:23]([F:26])([F:25])[F:24]
Reactant: Oc1ccccc1O
Reactant: FC(F)(F)C(Cl)=C(Cl)C(F)(F)F
Solvent: CCN(CC)CC
Solvent: CC#N
Product: FC(F)(F)C(Cl)C1(C(F)(F)F)Oc2ccccc2O1
Temperature: 75 °C
Reaction time: 2 h

Procedure:
110 g of pyrocatechol were dissolved in 1500 ml of acetonitrile, and 200 g of triethylamine were added. 235 g of 2,3-dichloro-1,1,1,4,4,4-hexafluoro-2-butene were added dropwise to the mixture at 75° C. The mixture was subsequently stirred at 75° C. for 2 hours. 1200 ml of the solvent were then distilled off in vacuo and the residue was taken up in 1500 ml of water. The product was extracted with diethyl ether and the organic phase was washed twice with 10% strength by weight aqueous sodium hydroxide solution and once with water. After drying with magnesium sulphate, the organic phase was concentrated and the residue was subjected to fractional distillation in vacuo. The yield was 258 g (=84% of theory). The boiling point was 63° C. under 12 mbar. The NMR spectra showed the following characteristic absorptions: 19F-NMR: -66.8 and -79.7 ppm. 1H-NMR: 4.71 ppm.
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][S:11]([CH3:14])(=[O:13])=[O:12].[Li+].[BH4-]>C1COCC1.CCOC(C)=O.Cl>[OH:2][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][S:11]([CH3:14])(=[O:13])=[O:12]
Reactant: COC(=O)c1ccccc1OS(C)(=O)=O
Agent: Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CS(=O)(=O)Oc1ccccc1CO
Temperature: 45 °C
Reaction time: 2 h

Procedure:
To a solution of 2-methanesulfonyloxybenzoic acid methyl ester (1.0 g, 4.3 mmol) in THF (10 mL) is added LiBH4 (375 mg, 17.2 mmol) in portions. The mixture is heated at 45° C. for 2 h then at 60° C. for 2 h. The mixture is diluted with EtOAc and ice and 1N HCl is added. The organic phase is separated and washed with 1N HCl and brine then dried over magnesium sulfate. The solvent is removed under reduced pressure to give the title compound as a solid.
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C:5]1[C:20]([CH3:21])=[CH:19][CH:18]=[CH:17][C:6]=1[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH3:16])=O.[Na].[OH2:23].[CH3:24][CH2:25][O:26][CH2:27][CH3:28]>C(COC)OC>[CH3:16][O:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[C:7]([C:6]1[CH:17]=[CH:18][CH:19]=[C:20]([CH3:21])[C:5]=1[O:4][CH2:3][O:2][CH3:1])=[CH:24][C:25]([O:26][CH2:27][CH3:28])=[O:23]
Reactant: O
Reactant: CCOCC
Reactant: COCOc1c(C)cccc1C(=O)c1ccccc1OC
Agent: [Na]
Solvent: COCCOC
Product: CCOC(=O)C=C(c1ccccc1OC)c1cccc(C)c1OCOC
Reaction time: 48 h

Procedure:
2-Methoxymethoxy-3-methyl-2'-methoxybenzophenone (17.5 g) was combined with the sodium salt of triethyl phosphonoacetate (2.2 equivalents) in 250 ml of dimethoxyethane and the mixture heated at reflux with stirring for 2 days. Water and ether were added and the organic phase was separated, extracted with water, dried over magnesium sulfate, filtered, and concentrated by evaporation under reduced pressure to obtain an oil. This was purified by preparative liquid chromatography, eluting with a 90:10 mixture of hexane and acetone, to obtain ethyl 3-(2-methoxyphenyl)-3-(2-methoxymethoxy-3-methylphenyl)propenoate as an intermediate consisting of a mixture of isomers. The assigned structure was consistent with the proton NMR spectrum. This was dissolved in 50 ml of tetrahydrofuran and treated with 61 ml of a solution of 1M lithium aluminum hydride in tetrahydrofuran at ambient temperature with stirring. The mixture was heated at reflux with stirring for 4 hours. It was then allowed to cool, was quenched with 10 percent sulfuric acid, and was diluted with ether. The organic phase was separated, extracted with water, dried over magnesium sulfate, filtered, and concentrated by evaporation under reduced pressure to obtain a crude product. This was purified by preparative liquid chromatography, eluting with a 95:5 mixture of hexane and acetone, to obtain 6.01 g of the title compound as a gum. The assigned structure was consistent with the proton NMR spectrum.
Reaction SMILES: [CH:1]1[CH2:5][CH:4]=[CH:3][CH:2]=1.C([C:8]([CH3:10])=[O:9])=C.[CH3:11][CH2:12]CCCC>>[C:8]([C:2]12[CH2:1][CH:5]([CH2:11][CH2:12]1)[CH:4]=[CH:3]2)(=[O:9])[CH3:10]
Reactant: C=CC(C)=O
Reactant: CCCCCC
Reactant: C1=CCC=C1
Product: CC(=O)C12C=CC(CC1)C2
Reaction time: 0.5 h

Procedure:
In a 1-liter three-necked flask equipped with a Dimroth reflux condenser and a thermometer, 200 ml of cyclopentadiene and 200 ml of hexane were placed, cooled on water bath, and 200 ml of methyl vinyl ketone was added dropwise thereto while stirred over 30 minutes, and then stirred for 30 minutes, to obtain acetyl norbornene.
Reaction SMILES: COC([NH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17])=O.[OH-].[Na+].C(O)(=O)C>C(O)C.O.[Au]>[NH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17]
Reactant: COC(=O)NCCCCCCCCCCC(=O)O
Agent: [Au]
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: O
Solvent: CCO
Product: NCCCCCCCCCCC(=O)O
Yield: 33.1 %

Procedure:
1.0 g (3.9×10-3 mol) of 11-(methoxycarbonylamino) undecanoic acid, is dissolved in 20 mL ethanol and added to 2.0 g (5.0×10-2 mol) sodium hydroxide in 2 mL water. The mixture is refluxed for 17 hours, and the resulting gold-colored solution is cooled and neutralized with acetic acid to a pH of 7. The neutralized solution is filtered to remove any salt and the filtrate is stripped to yield crude amino acid. The crude acid is dissolved in 50 mL of water, cooled in ice and filtered to yield 0.41 g (53%). Recrystallizion from 16 mL ethanol/water (3:1) resulted in 0.26 g (34% yield) 11-aminoundecanoic acid (mp. 189°-192° C., Lit. mp. 190°-192° C).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[CH2:27]Br)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[C:29]1([C:35]2[N:36]=[N:37][NH:38][N:39]=2)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[CH2:27][N:37]4[N:38]=[N:39][C:35]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)=[N:36]4)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4CBr)cc3)cc2)CC1
Reactant: c1ccc(-c2nn[nH]n2)cc1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4Cn4nnc(-c5ccccc5)n4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 6, Step 3, using 1-[4′-(4-bromomethyl-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester and 5-phenyl-2H-tetrazole.
Reaction SMILES: [C:1]1([N:7]=[N:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]([NH2:28])=O)=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Li+].[Al+3].[H-].[H-].[H-].C(OCC)C>O>[C:9]1([N:8]=[N:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1.[NH2:28][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][O:15][C:12]1[CH:11]=[CH:10][C:9]([N:8]=[N:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:14][CH:13]=1
Reactant: NC(=O)CCCCCCCCCCOc1ccc(N=Nc2ccccc2)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: O
Product: NCCCCCCCCCCCOc1ccc(N=Nc2ccccc2)cc1
Product: c1ccc(N=Nc2ccccc2)cc1
Reaction time: 24 h

Procedure:
A flask was charged with 1.008 g of the 11-[4-(phenylazo)phenyloxy]undecanamide, 0.624 g of aluminum lithium hydride, and 40 mL of dry diethylether, and the contents were put under reflux for 12 hours. The temperature was set back to a room temperature, and 20 mL of water was gradually dropped, so as to cause the excess aluminum lithium hydride to react with the water. Thereafter, the reaction solution was stirred for one day. Then, extraction from the reaction solution was performed three times by using 200 mL of diethylether, and the diethylether was removed by pressure-reduction. After that, a remaining supernatant was purified by recrystallization from a mixed solvent of chloroform and hexane. As a result, an intended amine derivative of 4-(phenylazo)benzene including a spacer group, i.e. 4-(11-aminoundecyloxy)azobenzene (azobenzene-O—(CH2)11NH2) was obtained at a 76% yield. A structure of the 4-(11-aminoundecyloxy)azobenzene was confirmed from a 1H-NMR spectrum and a 13C-NMR spectrum.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:19][C:20]#N)[N:5]([CH3:18])[C:6]=1[C:7](=[O:17])[C:8]1[CH:13]=[CH:12][C:11]([S:14]([CH3:16])=[O:15])=[CH:10][CH:9]=1.[OH-:22].[Na+].[OH2:24]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:19][C:20]([OH:24])=[O:22])[N:5]([CH3:18])[C:6]=1[C:7](=[O:17])[C:8]1[CH:13]=[CH:12][C:11]([S:14]([CH3:16])=[O:15])=[CH:10][CH:9]=1
Reactant: [OH-]
Reactant: O
Reactant: Cn1c(CC#N)cc(Cl)c1C(=O)c1ccc(S(C)=O)cc1
Agent: [Na+]
Solvent: CCO
Product: Cn1c(CC(=O)O)cc(Cl)c1C(=O)c1ccc(S(C)=O)cc1

Procedure:
A suspension of 0.50 g of 4-chloro-1-methyl-5-(p-methylsulfinylbenzoyl)-pyrrole-2-acetonitrile from Example XLV is stirred and refluxed in a solution of 0.13 g sodium hydroxide in 2 ml H2O and 2 ml 95% ethanol for 2 hours. The whole is then poured into water and the resulting aqueous solution is washed with chloroform. The washed aqueous solution is then acidified to pH 1 with 3N HCl. The solid which precipitates is collected by filtration and is recrystallized from 10:1 chloroform: water to give 4-chloro-1-methyl-5-(p-methylsulfinylbenzoyl)-pyrrole-2-acetic acid as a yellow solid; m.p. 222°-223° C.
Reaction SMILES: Cl[C:2]1[N:12]=[CH:11][C:10]([S:13]([N:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH3:23])[CH2:18][CH2:17]2)(=[O:15])=[O:14])=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[O-:24][CH2:25][CH3:26].[Na+]>C(O)C>[CH2:25]([O:24][C:2]1[N:12]=[CH:11][C:10]([S:13]([N:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH3:23])[CH2:18][CH2:17]2)(=[O:15])=[O:14])=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH3:26]
Reactant: CC[O-]
Reactant: CCOC(=O)c1cc(S(=O)(=O)N2CCN(CC)CC2)cnc1Cl
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)c1cc(S(=O)(=O)N2CCN(CC)CC2)cnc1OCC
Temperature: 40 °C
Yield: 33.9 %

Procedure:
A solution of Ethyl 2-chloro-5-(4-ethyl-1-piperazinylsulfonyl)nicotinoate (36.1 g, 0.1 mol) in ethanol (180 mL) was cooled to 10° C. with stirring. Sodium ethoxide (10.2 g, 0.15 mol) was added portionwise keeping the temperature below 20° C. The reaction mixture was then stirred at ambient temperature for 18 hours. The precipitate was filtered off and water (180 mL) added to the filtrate. The filtrate was then heated to 40° C. for 1 hour. Ethanol (180 mL) was then distilled off at ambient pressure and the remaining aqueous solution allowed to cool to ambient temperature. The precipitated product was then filtered off, washed with water and dried under vacuo at 50° C. to afford the title compound (12.6 g, 34%) as a light brown solid. M.p. 66-68° C. δ (CDCl3): 1.04 (3H, t), 1.39 (3H, t), 1.45 (3H, t), 2.41 (2H, q), 2.52 (4H, m), 3.08 (4H, m), 4.38 (2H, q), 2.57 (2H, q), 8.38 (1H, d), 8.61 (1H, d). m/z (Found:372 [M+H]+, 100%. C16H26N3O5S requires 372.46).
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][O:5][C:3]1=[O:4].[C:8](Cl)(=[O:10])[CH3:9].C([O-])([O-])=O.[K+].[K+]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:8]([O:1][CH:2]1[CH2:7][CH2:6][O:5][C:3]1=[O:4])(=[O:10])[CH3:9]
Reactant: O=C1OCCC1O
Reactant: CC(=O)Cl
Agent: CN(C)c1ccncc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: CC(=O)OC1CCOC1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.3 %

Procedure:
A mixture of racemic α-hydroxy-γ-butyrolactone (25 g; 0.25 mol), DMAP (1.5 g), acetylchloride (25.5 ml; 0.37 mol) in CH2Cl2 (325 mL) was added solid K2CO3 (50 g) in portions (slightly exothermic). The reaction mixture was stirred at room temperature overnight, filtered and evaporated to dryness. Column chromatography (Petrol ether 80-100:EtOAc=2:1) gave 26.4 g (75%) racemic α-acetoxy-γ-butyrolactone.