Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:24]=[CH:23][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH:20]([CH3:22])[CH3:21])[N:16]=[C:17]([CH3:19])[N:18]=1)[N:7]=3.[OH-:25].[K+].Cl>O1CCOCC1.O.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[CH:20]([N:15]1[C:14]([C:8]2[N:7]=[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]4[CH:3]=[C:2]([OH:25])[CH:24]=[CH:23][C:5]=43)[CH:9]=2)=[N:18][C:17]([CH3:19])=[N:16]1)([CH3:22])[CH3:21]
Reactant: [OH-]
Reactant: Cc1nc(-c2cn3c(n2)-c2ccc(Br)cc2OCC3)n(C(C)C)n1
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Solvent: CCOC(C)=O
Product: Cc1nc(-c2cn3c(n2)-c2ccc(O)cc2OCC3)n(C(C)C)n1
Temperature: 90 °C
Yield: 89.8 %

Procedure:
A mixture of 8-bromo-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (4.0 g, 10.3 mmol), KOH (1.73 g, 30.9 mmol), Pd2(dba)3 (189 mg, 0.2 mmol) and Xphos (350 mg, 0.82 mmol) in dioxane (20 mL) and H2O (10 mL) was purged with argon and heated at 90° C. for 45 min. The cooled reaction mixture was diluted with EtOAc and H2O then acidified with 1M HCl. The resulting precipitate was collected by filtration. The filtrate was separated, the aqueous phase extracted with further EtOAc and the combined organic extracts dried (MgSO4) and concentrated in vacuo. The resulting solid was combined with the original precipitate and triturated with Et2O. The resulting solid was collected by filtration and dried in vacuo affording 2-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-ol as a white solid (3.01 g, 90%). LCMS: RT 2.36 min [M+H]+ 326.2
Reaction SMILES: [CH3:1][N:2]1[CH:6]([CH2:7][CH2:8][C:9]2[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[C:11]([C:19]([F:22])([F:21])[F:20])[CH:10]=2)[CH:5]([CH2:23][C:24]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[NH:26][CH:25]=2)[NH:4][C:3]1=[O:33].[H-].[Na+].[CH3:36]I>O1CCCC1.C(OCC)(=O)C>[CH3:1][N:2]1[CH:6]([CH2:7][CH2:8][C:9]2[CH:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=[C:11]([C:19]([F:20])([F:21])[F:22])[CH:10]=2)[CH:5]([CH2:23][C:24]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[NH:26][CH:25]=2)[N:4]([CH3:36])[C:3]1=[O:33]
Reactant: CN1C(=O)NC(Cc2c[nH]c3ccccc23)C1CCc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CN1C(=O)N(C)C(Cc2c[nH]c3ccccc23)C1CCc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reaction time: 2 h

Procedure:
The compound of Example 1 (0.5 g) in tetrahydrofuran (5 ml) was treated with sodium hydride (43 mg of a 60% dispersion in oil) under a nitrogen atmosphere with stirring. After 5 minutes methyl iodide (0.28 g) was added and stirring continued for 2 hours. The reaction was diluted with ethyl acetate, washed with water, dried and concentrated. The residue was purified by chromatography on silica gel eluting with ethyl acetate-petroleum ether and crystallised from ethyl acetate-petroleum ether to give the title compound, mp 202°-205° C.; found: C, 59.88; H, 4.23; N, 8.42. C24H21F6N3O requires C, 59.88; H, 4.40; N, 8.73.
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]=[C:8]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:26][CH:25]=2)[C:9]2[CH:15]=[CH:14][C:13]([C:16]3[C:21]([CH3:22])=[CH:20][CH:19]=[CH:18][N:17]=3)=[N:12][C:10]=2[N:11]=1)=[O:5])C.O[Li].O.Cl>C1COCC1.O>[C:30]([C:27]1[CH:26]=[CH:25][C:24]([NH:23][C:8]2[C:9]3[CH:15]=[CH:14][C:13]([C:16]4[C:21]([CH3:22])=[CH:20][CH:19]=[CH:18][N:17]=4)=[N:12][C:10]=3[N:11]=[C:6]([C:4]([OH:5])=[O:3])[N:7]=2)=[CH:29][CH:28]=1)([CH3:33])([CH3:32])[CH3:31]
Reactant: CCOC(=O)c1nc(Nc2ccc(C(C)(C)C)cc2)c2ccc(-c3ncccc3C)nc2n1
Agent: Cl
Agent: [Li]O
Solvent: O
Solvent: C1CCOC1
Product: Cc1cccnc1-c1ccc2c(Nc3ccc(C(C)(C)C)cc3)nc(C(=O)O)nc2n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Dissolve 4-(4-t-butyl-phenylamino)-7-(3-methyl-pyridin-2-yl)-pyrido[2,3-d]pyrimidine-2-carboxylic acid ethyl ester (25 mg, 0.57 mmol) and LiOH.H2O (8 mg, 0.17 mmol) in a solution of THF (2.5 mL) and H2O (0.2 mL). Stir the mixture overnight at room temperature. Add water 10 mL and acidify with 3 N HCl. Extract the mixture with EtOAc (3×10 mL). Wash the combined organic extracts with brine and dry over Na2SO4. Remove the solvent under reduced pressure to yield the title compound. MS 414.18 (M+1).
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]([F:16])([F:15])[F:14])=[N:5][N:4]=[C:3]1[C:17]12[CH2:24][CH2:23][C:20]([C:25]([OH:27])=O)([CH2:21][CH2:22]1)[CH2:19][CH2:18]2.F[P-](F)(F)(F)(F)F.CN(C)C=[N+](C)C.C(N(CC)CC)C.[NH2:49][NH2:50]>CN(C=O)C>[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]([F:16])([F:15])[F:14])=[N:5][N:4]=[C:3]1[C:17]12[CH2:24][CH2:23][C:20]([C:25]([NH:49][NH2:50])=[O:27])([CH2:19][CH2:18]1)[CH2:21][CH2:22]2
Reactant: Cn1c(-c2ccccc2C(F)(F)F)nnc1C12CCC(C(=O)O)(CC1)CC2
Reactant: NN
Agent: CN(C)C=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cn1c(-c2ccccc2C(F)(F)F)nnc1C12CCC(C(=O)NN)(CC1)CC2

Procedure:
A portion of solid (4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]octane-1-carboxylic acid 1-D (2.0 g, 5.27 mmol) was dissolved in anhydrous DMF (30 ml) and treated with N,N,N′,N′-tetramethylformamidinium hexafluorophosphate (2.09 g, 7.91 mmol), triethyl amine (2.3 mL, 16.50 mmol), and hydrazine (0.50 mL, 15.93 mmol) at room temperature and a nitrogen atmosphere overnight. The solvent was removed in vacuo, and the residue was redissolved in methylene chloride (700 ml) and washed with saturated aqueous sodium bicarbonate, water, and brine. The product was dried over MgSO4 and the solvent removed to afford 13-A as a white powder. MS (ESI+)=394.13 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:11][OH:12])=[C:6]([NH:8][CH:9]=[O:10])[CH:7]=1.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:11]=[O:12])=[C:6]([NH:8][CH:9]=[O:10])[CH:7]=1
Reactant: O=CNc1cc(Cl)ccc1CO
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: O=CNc1cc(Cl)ccc1C=O
Temperature: 20 °C
Reaction time: 24 h

Procedure:
A mixture of 1.40 g of the product from stage 1 and 3.40 g of pyridinium dichromate in 350 ml of anhydrous dichloromethane was stirred for 24 hours at 20° C. The solution was then filtered and the filtrate was concentrated by evaporation in vacuo. The residue was purified by flash chromatography on silica gel with ethyl acetate/cyclohexane (1/1) as eluent, 0.88 g (64% of theory) of the title compound being obtained in crystalline form.
Reaction SMILES: Cl[C:2]1[N:11]([CH3:12])[CH:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:19])[CH:8]=2)[N:3]=1.[N-:20]=[N+:21]=[N-:22].[Na+]>CS(C)=O>[Cl:19][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]1[N:20]=[N:21][N:22]=[C:2]1[N:11]([CH3:12])[CH:10]2[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CN1C(Cl)=Nc2ccc(Cl)cc2C1c1ccccc1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CN1c2nnnn2-c2ccc(Cl)cc2C1c1ccccc1
Temperature: 100 °C
Yield: 96.5 %

Procedure:
To a solution of 2.33 g of 2,6-dichloro-3,4-dihydro-3-methyl-4-phenylquinazoline in 30 ml of dimethylsulfoxide was added 1.0 g of sodium azide. The mixture was heated at 100° C. for 3 hours and then poured into ice-water. The precipitate formed was collected by filtration, washed with water and dried to give 2.3 g of 7-chloro-4,5-dihydro-4-methyl-5-phenyltetrazolo[1,5-a]quinazoline, m.p. 280° C.
Reaction SMILES: [CH3:1][CH:2]([C@@H:13]1[C@:30]2([CH3:31])[C@H:16]([C:17]3[C@H:27]([CH2:28][CH2:29]2)[C@:25]2([CH3:26])[C:20]([CH2:21][C@@H:22]([O:37]C(OC)=O)[CH2:23][C@@H:24]2[O:32]C(OC)=O)=[CH:19][CH:18]=3)[CH2:15][CH2:14]1)[CH2:3]S(C1C=CC=CC=1)(=O)=O.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH2:52](Br)[CH2:53][CH:54]([CH3:56])[CH3:55].O>O1CCCC1>[CH3:55][CH:54]([CH2:53][CH2:52][CH2:3][C@H:2]([C@@H:13]1[C@:30]2([CH3:31])[C@H:16]([C:17]3[C@H:27]([CH2:28][CH2:29]2)[C@:25]2([CH3:26])[C:20]([CH2:21][C@@H:22]([OH:37])[CH2:23][C@@H:24]2[OH:32])=[CH:19][CH:18]=3)[CH2:15][CH2:14]1)[CH3:1])[CH3:56]
Reactant: COC(=O)O[C@@H]1CC2=CC=C3[C@@H]4CC[C@H](C(C)CS(=O)(=O)c5ccccc5)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(=O)OC)C1
Reactant: CC(C)CCBr
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O)[C@]4(C)[C@H]3CC[C@]12C
Temperature: -70 °C
Reaction time: 0.5 h
Yield: 62.8 %

Procedure:
In 1 ml of tetrahydrofuran was dissolved 35 mg of 20-methyl-1α,3β-bis(methoxycarbonyloxy)-21-phenylsulfonylpregna-5,7-diene and the solution was cooled to -70° C. To the solution was added 0.8 ml of 0.1N solution of lithium hexamethyldisilazide in tetrahydrofuran. The resulting mixture was stirred for 30 minutes. After addition of 30 mg of isoamyl bromide, the mixture was stirred for 4 hours while the temperature was gradually raised to room temperature. The reaction mixture was poured into water and extracted with diethyl ether. The extract was washed with an aqueous solution of sodium hydrogen carbonate and an aqueous solution of sodium chloride, then dried over sodium sulfate and concentrated. The residue was dissolved in 1 ml of methanol and treated with 500 mg of 6% sodium amalgam in the presence of 0.5 ml of disodium hydrogen phosphate at ambient temperature for 1 hour. The reaction mixture was poured into water and extracted with diethyl ether. The extract was washed with an aqueous solution of sodium chloride, dried over sodium sulfate and concentrated. The residue was dissolved in 1 ml of methanol, 10 mg of potassium carbonate was added, and the mixture was stirred for 12 hours. The reaction mixture was then subjected to the isolation and purification procedure of Reference Example 8 to give 15 mg of cholesta-5,7-diene-1α,3β-diol which showed the same 1H NMR spectrum as that obtained in Reference Example 8.
Reaction SMILES: [NH2:1][C:2]1[C:44]([NH2:45])=[CH:43][CH:42]=[CH:41][C:3]=1[C:4]([NH:6][C:7]1[CH:38]=[CH:37][C:10]([C:11]([N:13]([CH3:36])[C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:15]=2[O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([N:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)=[O:28])=[O:12])=[CH:9][C:8]=1[O:39][CH3:40])=[O:5].C(O)(=O)C.[N:50]([O-])=O.[Na+].C(=O)(O)[O-].[Na+]>O.C(Cl)(Cl)Cl>[NH:45]1[C:44]2[CH:43]=[CH:42][CH:41]=[C:3]([C:4]([NH:6][C:7]3[CH:38]=[CH:37][C:10]([C:11]([N:13]([CH3:36])[C:14]4[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:15]=4[O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([N:29]4[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]4)=[O:28])=[O:12])=[CH:9][C:8]=3[O:39][CH3:40])=[O:5])[C:2]=2[N:1]=[N:50]1
Reactant: COc1cc(C(=O)N(C)c2ccc(C)cc2OCCCCCC(=O)N2CCN(C)CC2)ccc1NC(=O)c1cccc(N)c1N
Reactant: O=N[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: CC(=O)O
Product: COc1cc(C(=O)N(C)c2ccc(C)cc2OCCCCCC(=O)N2CCN(C)CC2)ccc1NC(=O)c1cccc2[nH]nnc12
Temperature: 25 °C
Yield: 66.3 %

Procedure:
To 4-(2,3-diaminobenzoyl)amino-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamide (120 mg) were added acetic acid (47 mg) and water (0.5 ml) and the suspension was stirred at ambient temperature until a clear solution was obtained. After being cooled to 5° C. a cold solution of sodium nitrite (15 mg) in water (0.3 ml) was added all at once to the solution. The reaction mixture as stirred at 5° C. for 5 minutes and then the temperature was raised to 75° C. and stirred for 10 minutes. The reaction mixture was cooled to 20° C. and the solution was stirred in an ice water bath for 1 hour. To the reaction mixture were added saturated aqueous sodium bicarbonate solution and chloroform and the organic layer was separated. The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine and dried over magnesium sulfate. The solvent was evaporated and the residue was purified by preparative thin-layer chromatography (chloroform-methanol=10:1) to give 4-(1H-benzotriazol-4-yl)carbonylamino-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamide (81 mg) to give a powder.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[C:7]([CH2:9][C:10]([O:12][CH3:13])=[O:11])#[N:8].Cl[C:15]1[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=1[N+:22]([O-:24])=[O:23].Cl>O.C(OCC)(=O)C.CN(C)C=O>[Cl:21][C:19]1[CH:18]=[CH:17][C:16]([N+:22]([O-:24])=[O:23])=[C:15]([CH:9]([C:7]#[N:8])[C:10]([O:12][CH3:13])=[O:11])[CH:20]=1
Reactant: O=[N+]([O-])c1ccc(Cl)cc1Cl
Reactant: COC(=O)CC#N
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)C(C#N)c1cc(Cl)ccc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 87.7 %

Procedure:
In a flask made of glass equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel and having an inner volume of 200 ml were charged 7.13 g (51.6 mmol) of potassium carbonate, 20 ml of N,N-dimethylformamide, 5.06 g (50.6 mmol) of methyl cyanoacetate with a purity of 99% and 5.00 g (25.8 mmol) of 2,4-dichloronitrobenzene with a purity of 99% under argon atmosphere, and under stirring, the mixture was reacted at 45° C. for 4 hours. After completion of the reaction, the mixture was cooled to room temperature, 100 ml of ethyl acetate was added to the mixture, and 12.9 ml (77.4 mmol) of 6 mol/l hydrochloric acid was gradually added dropwise to the mixture while stirring. Then, after adding 50 ml of water to the mixture, the organic layer was separated, and washed with 50 ml of a saturated saline solution, and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography (filler: Daisogel 1002W, eluent: hexane:ethyl acetate=20:1 (volume ratio)) to obtain 5.76 g (isolation yield: 83%) of methyl 2-(5-chloro-2-nitrophenyl)-2-cyanoacetate as white crystals with a purity of 95% (areal percentage by high performance liquid chromatography).
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[C:12]([O:23][CH3:24])(=[O:22])[CH2:13][C@H:14]([CH2:16][CH2:17][CH:18]=C(C)C)[CH3:15].S([O-])([O-])(=O)=S.[Na+].[Na+].O.O.I(O)(=O)(=O)=O>ClCCl.C1COCC1.O>[CH3:15][C@@H:14]([CH2:16][CH2:17][CH:18]=[O:9])[CH2:13][C:12]([O:23][CH3:24])=[O:22]
Reactant: COC(=O)C[C@@H](C)CCC=C(C)C
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])O
Solvent: O
Solvent: ClCCl
Solvent: C1CCOC1
Product: COC(=O)C[C@@H](C)CCC=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 100.8 %

Procedure:
To a solution of 7.76 g (36 mmol) of 80% m-chloroperbenzoic acid in 200 ml of dry dichloromethane is added a solution of 6.00 g (32.6 mmol) of (S)-methyl citronellate 30 (prepared in 31-(1)) in 50 ml of dry dichloromethane, and the mixture is stirred at room temperature for one hour. The reaction mixture are added 5% aqueous solution of sodium thiosulfate and a dilute aqueous solution of sodium hydrogencarbonate, and the mixture is extracted with dichloromethane twice. The extract is washed with a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. To a solution of the residue in 80 ml of THF is added a solution of 8.90 g (39 mmol) of periodic acid dihydrate in 80 ml of THF at 0° C. After additional stirring at room temperature for 20 minutes, the reaction mixture is diluted with water, and extracted with ether twice. The extract is washed with water, a saturated aqueous solution of sodium hydrogencarbonate, and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure to give 5.2 g of the crude desired aldehyde 31 as an oil, which is employed in the next step without further purification.
Reaction SMILES: [CH3:1][CH:2]([CH3:7])[CH2:3][C:4](=[O:6])[CH3:5].O.[N+:9]([CH:12]([CH:15]=O)[CH:13]=O)([O-:11])=[O:10].[Na].[OH-].[Na+]>C(O)C.O>[CH:2]([C:3]1[CH:15]=[C:12]([N+:9]([O-:11])=[O:10])[CH:13]=[CH:5][C:4]=1[OH:6])([CH3:7])[CH3:1]
Reactant: CC(=O)CC(C)C
Reactant: O=CC(C=O)[N+](=O)[O-]
Agent: [Na+]
Agent: [Na]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CC(C)c1cc([N+](=O)[O-])ccc1O
Temperature: 25 °C
Reaction time: 8 h
Yield: 54 %

Procedure:
4-Methyl-2-pentanone (4.85 g, 48 mmol) in 40 mL of ethanol was added dropwise to a solution of sodium nitromalonaldehyde monohydrate (7.61 g, 48 mmol) in 40 mL of water. NaOH (48 ml of 1N aqueous solution) was then added to the reaction mixture. The mixture was stirred at room temperature overnight, and solvent was removed under reduced pressure. The residue was diluted with water and neutralized, then extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography with silica eluting with 15% ethyl acetate in hexanes to yield 4.7 g of 2-isopropyl-4-nitrophenol.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH2:8][CH2:7][CH2:6]2.[CH:13](=O)[CH2:14][CH3:15]>[Pd].C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][CH2:14][CH3:15])[CH2:8][CH2:7][CH2:6]2
Reactant: CCC=O
Reactant: COc1ccc2c(c1)CCCN2
Agent: [Pd]
Solvent: CCO
Product: CCCN1CCCc2cc(OC)ccc21
Yield: 54 %

Procedure:
A solution of 148.6 g. of 6-methoxy-1,2,3,4-tetrahydroquinoline and 58 g. of propionaldehyde in 275 ml. of ethanol was hydrogenated at 60 psi over 15 g. of 15% palladium on carbon at room temperature for 2 hours and then at 50° C. overnight. The catalyst was removed by filtration and the filtrate concentrated to give a brown oil which was distilled to give 100.5 g. of 6-methoxy-1-n-propyl-1,2,3,4-tetrahydroquinoline (54% yield) as an oil boiling in the range 115°-128° C. at 0.02 Torr.
Reaction SMILES: C(N1C(=O)N(CCO)C(=O)N(CCO)C1=O)CO.C(OC)(=O)C1C=CC(C(OC)=O)=CC=1.[CH:33]1[C:42]2[C:37](=[CH:38][C:39]([C:43]([O:45]C)=[O:44])=[CH:40][CH:41]=2)[CH:36]=[CH:35][C:34]=1[C:47]([O:49]C)=[O:48].C1C(CC2C=CC(N)=CC=2)=CC=C(N)C=1>C1(C)C(O)=CC=CC=1.C(O)CO>[CH:33]1[C:42]2[C:37](=[CH:38][C:39]([C:43]([OH:45])=[O:44])=[CH:40][CH:41]=2)[CH:36]=[CH:35][C:34]=1[C:47]([OH:49])=[O:48]
Reactant: COC(=O)c1ccc2cc(C(=O)OC)ccc2c1
Agent: COC(=O)c1ccc(C(=O)OC)cc1
Agent: Cc1ccccc1O
Agent: Nc1ccc(Cc2ccc(N)cc2)cc1
Solvent: OCCO
Product: O=C(O)c1ccc2cc(C(=O)O)ccc2c1

Procedure:
72.9 g of ethylene glycol, 192.2 g of THEIC, 83.3 g of dimethyl terephthalate, 104.4 g of dimethyl 2,6-naphthalenedicarboxylate, 220.1 g of trimellitic anhydride, 112.0 g of 4,4'-diaminodiphenylmethane and 0.7 g of tetra-n-butyl titanate are heated at 200° C. to prepare a polyesterimide resin. 96.8 g of distillate are obtained. At 200° C., the batch is diluted with 808.5 g of cresol. The cooled cresolic solution is diluted with 288.5 g of solvent naphtha and catalysed with 11.4 g of cresyl titanate.
Reaction SMILES: [ClH:1].[O:2]=[C:3]1[CH2:9][CH2:8][CH2:7][NH:6][CH2:5][CH:4]1[C:10]([O:12][CH2:13][CH3:14])=[O:11].[H][H]>C(O)C.[Ru]>[ClH:1].[OH:2][C@@H:3]1[CH2:9][CH2:8][CH2:7][NH:6][CH2:5][C@H:4]1[C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: [H][H]
Reactant: CCOC(=O)C1CNCCCC1=O
Agent: [Ru]
Agent: Cl
Solvent: CCO
Product: CCOC(=O)[C@@H]1CNCCC[C@H]1O

Procedure:
As in Example 2, 23.2 g of ethyl 4-oxo-azepan-3-carboxylate hydrochloride in 90 ml of ethanol were hydrogenated with a solution of 36.1 mg of the ruthenium catalyst in 10 ml of ethanol under 40 bar hydrogen pressure at 30° C. for 21 hours and at 50° C. for 3 hours. The residue, consisting of about 80% 3R,4R and 20% 3S,4R isomers, was triturated with tetrahydrofuran and ethanol at 50° C. for half an hour and at room temperature for 4 hours. The crystals were filtered off under suction, washed with a small amount of tetrahydrofuran/ethanol and dried to constant weight at 50° C./20 mbar, to yield 13.3 g of enantiomerically pure ethyl (3R,4R)-4-hydroxy-azepan-3-carboxylate hydrochloride in the form of white crystals.
Reaction SMILES: [OH2:1].[CH:2]([C:4]1[CH:5]=[C:6]([C:10](=[N:17][O:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])[C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[CH:7]=[CH:8][CH:9]=1)=[O:3]>[Ag-]=O.C(O)C>[C:23]([CH2:22][CH2:21][CH2:20][CH2:19][O:18][N:17]=[C:10]([C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1)[C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=1)[C:2]([OH:1])=[O:3])([OH:25])=[O:24]
Reactant: O=Cc1cccc(C(=NOCCCCC(=O)O)c2cccnc2)c1
Reactant: O
Agent: O=[Ag-]
Solvent: CCO
Product: O=C(O)CCCCON=C(c1cccnc1)c1cccc(C(=O)O)c1
Reaction time: 1 h

Procedure:
A mixture of 6.5 parts of silver(I) oxide, 50 parts of water, 63 parts of ethanol and 6.5 parts of 5-[[[(3-formylphenyl)(3-pyridinyl)methylen]amino]oxy]pentanoic acid is stirred for 1 hour at a somewhat elevated temperature to give 3-[[(4-carboxybutoxy)imino](3-pyridinyl)methyl]benzoic acid (compound 126).
Reaction SMILES: [C:1]([NH:4][C:5]1[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7]([O:18][CH3:19])[CH:6]=1)(=[O:3])[CH3:2].[CH3:20]S(OC)(=O)=O.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.[Cl-].[Na+].O>[CH3:19][O:18][C:7]1[CH:6]=[C:5]([N:4]([CH3:20])[C:1](=[O:3])[CH3:2])[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][C:8]=1[C:9]([O:11][CH3:12])=[O:10]
Reactant: COC(=O)c1cc([N+](=O)[O-])c(NC(C)=O)cc1OC
Reactant: COS(C)(=O)=O
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1cc([N+](=O)[O-])c(N(C)C(C)=O)cc1OC
Temperature: 25 °C
Reaction time: 36 h

Procedure:
A mixture of methyl 4-acetamido-2-methoxy-5-nitrobenzoate (2.0 g; 7.5 mmol), methyl methanesulfonate (0.85 g; 7.7 mmol) and K2CO3 (2.0 g; 14.5 mmol) in DMF (20 mL) was stirred for 36 h at rt. The mixture was thereafter poured into brine and extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated to give the crude sub-title compound.
Reaction SMILES: OCCCN[C:6](=O)[C@H:7]([C:9]([CH2:12][OH:13])(C)C)[OH:8].CN(C1C=CC=CN=1)C.C([O:27][C:28](=[O:30])[CH3:29])(=O)C>>[CH3:6][C:7]([CH2:9][C:12]([CH2:29][C:28]([OH:27])=[O:30])=[O:13])=[O:8]
Reactant: CC(C)(CO)[C@H](O)C(=O)NCCCO
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccccn1
Product: CC(=O)CC(=O)CC(=O)O
Temperature: 80 °C
Reaction time: 9 h

Procedure:
D-panthenol (177 grams, 0.572 moles) and polymer bound dimethylaminopyridine (2.7 grams) were added to a flask. Acetic anhydride (192.5 grams, 4.4 moles) was slowly added to the stirring mixture, and the resultant exotherm was controlled when the temperature reached 80° C. The mixture was heated at 80° C. and stirred for 9 hours. The flask was then fitted for vacuum distillation, and the acetic acid was removed under reduced pressure to a concentration of about 4% w/w. The catalyst (P-DMAP) was filtered out from the reaction mixture. The solution was treated with a 50% w/w solution of sodium hydroxide in a volume sufficient to neutralize the residual acetic acid, and the resultant solids of sodium acetate were removed by filtration. The residual water was then removed under vacuum to afford about 78% of the desired product, D-panthenyl triacetate.