Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.F[C:10]1[CH:23]=[CH:22][C:13]([C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:15])=[CH:12][CH:11]=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>C1(C)C=CC=CC=1>[I:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:22]2[CH:23]=[CH:10][CH:11]=[CH:12][C:13]=2[C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:15])=[CH:4][CH:3]=1
Reactant: Oc1ccc(I)cc1
Reactant: O=C(c1ccccc1)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: O=C(c1ccccc1)c1ccccc1Oc1ccc(I)cc1
Temperature: 160 °C
Reaction time: 2 h
Yield: 79.1 %

Procedure:
A 1000 mL 3-necked round-bottomed flask fitted with a Dean-Stark trap, condenser, stir-bar and nitrogen gas adaptor was charged with 4-iodophenol (19.0 g, 0.086 mol), 4-fluorobenzophenone (15.72 g, 0.079 mol), potassium carbonate (7.16 g, 0.0518 mol), DMF (157 mL) and toluene (16 mL). The resulting mixture was stirred and refluxed for 2 hours (solution temperature ˜160° C.) under nitrogen atmosphere. Water was collected at the trap during this period of time. After 2 hours, the reaction was cooled to room temperature, and water (400 mL) was added to the reaction mixture and the desired product precipitated out of solution as a cream white solid. The product was further purified by re-crystallization isopropanol (400 mL) to give the desired product as a white crystalline solid (25 g, 87% yield).
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([S:14]([OH:17])(=O)=[O:15])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:20])=O>CN(C=O)C>[O:1]([C:8]1[CH:13]=[CH:12][C:11]([S:14]([Cl:20])(=[O:17])=[O:15])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: O=S(=O)(O)c1ccc(Oc2ccccc2)cc1
Solvent: CN(C)C=O
Product: O=S(=O)(Cl)c1ccc(Oc2ccccc2)cc1
Reaction time: 6 h

Procedure:
The sulphonic acid (2a) was dissolved in an excess of thionyl chloride (30 mL), a catalytic amount of DMF (cat) was added, and the resulting mixture was stirred for 6 h at reflux. The solvent was evaporated and the residue dissolved in Et20 (40 mL). The ether solution was washed with 5% aqueous NaOH (3×40 mL) and water (6×40 mL), dried over anhydrous MgSO4, filtered, and concentrated in vacuo. After drying in high vacuum overnight, the pure product was obtained as a white solid. Yield 63%: 2.09 g, 7.44 mmol, (light yellow syrup). 1H-NMR (CDCl3): δ 7.44 (d, 3J=9.1 Hz, 2H, ArH), 7.38 (d, 3J=9.1 Hz, 2H, ArH), 7.19 (t, 1H, ArH), 7.12 (d, 3J=9.1 Hz, 2H, ArH), 6.98 (d, 3J=9.1 Hz, 2H, ArH)
Reaction SMILES: S(C1C=CC(C)=CC=1)([O-])(=O)=O.[NH+]1C=CC=CC=1.[CH:18]([O:20][CH2:21][CH3:22])=[CH2:19].[OH:23][CH:24]([CH:33]1[CH2:38][CH2:37][C:36](=[O:39])[CH2:35][CH2:34]1)[CH2:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(Cl)Cl>[CH2:18]([O:20][CH:21]([O:23][CH:24]([CH:33]1[CH2:38][CH2:37][C:36](=[O:39])[CH2:35][CH2:34]1)[CH2:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH3:22])[CH3:19]
Reactant: C=COCC
Reactant: O=C1CCC(C(O)COc2ccccc2)CC1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CCOC(C)OC(COc1ccccc1)C1CCC(=O)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Pyridinium tosylate (15 mg, 0.06 mmol) and ethyl vinyl ether (339 mg, 450 μl, 4.70 mmol) were added to a solution of 4-(1-hydroxy-2-phenoxyethyl)cyclohexanone (919 mg, 3.92 mmol) in anhydrous methylene chloride (20 ml) and the mixture was stirred at room temperature overnight. Methylene chloride (20 ml) was then added to the mixture and the mixture was washed with water, 5% strength sodium bicarbonate solution and saturated sodium chloride solution (50 ml of each). The organic phase was dried with sodium sulfate and concentrated in vacuo.
Reaction SMILES: [CH:1](=[C:8]1[C:20]2[N:19]3[CH:21]=[CH:22][N:23]=[C:18]3[C:17](=[O:24])[NH:16][C:15]=2[C:14]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C)C=O.[H][H]>[Pd].CO>[CH2:1]([CH:8]1[C:20]2[N:19]3[CH:21]=[CH:22][N:23]=[C:18]3[C:17](=[O:24])[NH:16][C:15]=2[C:14]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]1=2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [H][H]
Reactant: O=c1[nH]c2c3ccccc3c(=Cc3ccccc3)c2n2ccnc12
Agent: [Pd]
Solvent: CN(C)C=O
Solvent: CO
Product: O=c1[nH]c2c(n3ccnc13)C(Cc1ccccc1)c1ccccc1-2
Yield: 37.3 %

Procedure:
A mixture of 0.4 g of 10-benzylidene-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one, 90 ml of dimethylformamide and 10 ml of methanol is hydrogenated at a temperature in the region of 20° C. at a pressure of 1.9 bar of hydrogen for 3 hours in the presence of 10% palladium on charcoal. The catalyst is then filtered off under inert atmosphere and the solvents are evaporated off. The brown solid obtained (0.37 g) is purified by chromatography on a column of silica (35 g) with a mixture of dichloromethane and methanol (90/10 by volume). After trituration with 5 ml of dichloromethane, filtration and drying at 100° C., 0.15 g of 10-benzyl-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one is obtained, in the form of a beige solid melting above 260° C. (Analysis % calculated C: 76.66, H: 4.82, N: 13.41, O: 5.11, % found C: 76.3, H: 4.6, N: 13.4).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:18]([CH2:31][CH3:32])=[CH:19][C:20]([CH:27]4[CH2:30][CH2:29][CH2:28]4)=[C:21]([CH:26]=3)[C:22]([O:24]C)=O)=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[N:2].O.[NH2:34][NH2:35]>CO>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:18]([CH2:31][CH3:32])=[CH:19][C:20]([CH:27]4[CH2:30][CH2:29][CH2:28]4)=[C:21]([CH:26]=3)[C:22]([NH:34][NH2:35])=[O:24])=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[N:2]
Reactant: NN
Reactant: CCc1cc(C2CCC2)c(C(=O)OC)cc1C(=O)N1CCC(c2ccc(C#N)cc2)CC1
Solvent: CO
Solvent: O
Product: CCc1cc(C2CCC2)c(C(=O)NN)cc1C(=O)N1CCC(c2ccc(C#N)cc2)CC1
Temperature: 80 °C
Reaction time: 8 h
Yield: 53 %

Procedure:
To a solution of methyl 5-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-4-ethylbenzoate (compound 215.5, 2.15 g, 4.99 mmol, 1.00 equiv) in methanol (20 mL), was added hydrazine hydrate (80%, 15 mL) batchwise. The reaction was stirred at 80° C. overnight. After cooling to ambient temperature, the mixture was concentrated under reduced pressure. The residue was extracted with dichloromethane (2×100 mL). The combined organic layers were dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography with dichloromethane/methanol (100:1) to furnish 1.13 g (53%) of the desired product as a pinkish solid.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([C:6]2[N:11]3[N:12]=[C:13]([NH2:15])[N:14]=[C:10]3[CH:9]=[CH:8][CH:7]=2)=[CH:2]1.[CH:16]1([C:21](Cl)=[O:22])[CH2:20][CH2:19][CH2:18][CH2:17]1>>[O:1]1[CH:5]=[CH:4][C:3]([C:6]2[N:11]3[N:12]=[C:13]([NH:15][C:21]([CH:16]4[CH2:20][CH2:19][CH2:18][CH2:17]4)=[O:22])[N:14]=[C:10]3[CH:9]=[CH:8][CH:7]=2)=[CH:2]1
Reactant: O=C(Cl)C1CCCC1
Reactant: Nc1nc2cccc(-c3ccoc3)n2n1
Product: O=C(Nc1nc2cccc(-c3ccoc3)n2n1)C1CCCC1

Procedure:
The title compound was prepared following procedure and work up described for example 19, but starting from 5-(3-furyl)[1,2,4]triazolo[1,5-a]pyridin-2-amine ((A2), 50 mg; 0.25 mmol; 1.0 eq.) and cyclopentanecarbonyl chloride (66 mg; 0.50 mmol; 2.0 eq.) as a white powder (64.1 mg, 86%). HPLC, Rt: 3.11 min. (purity 82.7%). LC/MS, M+(ESI): 297.4, M−(ESI): 295.3.
Reaction SMILES: [C:1]1([CH:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:20][N:21]([CH3:31])[C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=1>ClCCl>[CH3:20][N:21]([CH3:31])[C:22]1[CH:30]=[CH:29][C:25]([C:26]([N:11]2[CH2:10][CH2:9][CH:8]([CH:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:13][CH2:12]2)=[O:27])=[CH:24][CH:23]=1
Reactant: CN(C)c1ccc(C(=O)O)cc1
Reactant: c1ccc(C(c2ccccc2)C2CCNCC2)cc1
Solvent: ClCCl
Product: CN(C)c1ccc(C(=O)N2CCC(C(c3ccccc3)c3ccccc3)CC2)cc1
Reaction time: 24 h

Procedure:
To a solution of 150 parts of 4-(diphenylmethyl)piperidine and 99 parts of 4-(dimethylamino)benzoic acid in 4000 parts of dichloromethane is added a solution of 123 parts of N,N1 -methanetetraylbiscyclohexanamine in 1330 parts of dichloromethane. The resultant mixture is stirred for 6 hours, whereupon a further 25 parts of 4-(dimethylamino)benzoic acid and 30 parts of N,N1 -methanetetraylbiscyclohexanamine is introduced and stirring continued thereafter for 24 hours. The reaction mixture is then filtered, and the filtrate is stripped of solvent by vacuum distillation. The residue is taken up in ether; and the ether solution is consecutively washed with 5% hydrochloric acid, water, and 5% ammonium hydroxide, then dried over anhydrous potassium carbonate and finally stripped of solvent by vacuum distillation. The residue is recrystallized from a mixture of benzene and hexane to give 1-[4-(dimethylamino)benzoyl]-4-(diphenylmethyl)piperidine melting at 177°-179°.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[CH:7][C:8]([OH:16])=[C:9]([C:11]([CH3:15])([CH3:14])[C:12]#[N:13])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.Cl[C:27]([O:29][CH3:30])=[O:28]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:27](=[O:28])([O:29][CH3:30])[O:16][C:8]1[CH:7]=[CH:6][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:10][C:9]=1[C:11]([C:12]#[N:13])([CH3:15])[CH3:14]
Reactant: COC(=O)Cl
Reactant: CC(C)(C)c1ccc(O)c(C(C)(C)C#N)c1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)Oc1ccc(C(C)(C)C)cc1C(C)(C)C#N
Temperature: 0 °C
Reaction time: 12 h

Procedure:
To a stirred mixture of compound 15 (126.6 g, 0.564 mol), DMAP (6.0 g) and DIEA (188 g, 1.46 mol) in anhydrous DCM (1500 mL) was added dropwise methyl chloroformate (110 g, 1.17 mol) in anhydrous DCM (300 mL) at 0° C. within 2 hours. After stirring for 12 hours at 0° C., ice-water (1.5 L) was added and the mixture was stirred at 0° C. for 30 minutes. The organic layer was separated and washed with 1 N HCl, water, and brine. The DCM solution was dried over MgSO4 and concentrated in vacuo to give compound 16 as a yellow solid. 1H NMR (DMSO-d6; 400 MHz) δ 7.47 (m), δ 7.39 (d), δ 7.24 (d), δ 3.84 (s), δ 1.71 (s), δ 1.30 (s).
Reaction SMILES: [CH:1](=[O:4])[CH2:2][CH3:3].[CH3:5][CH:6]([CH2:9][CH2:10][CH3:11])[CH:7]=O.[OH-].[Na+].O>>[CH3:3][C:2](=[CH:5][CH:6]([CH3:7])[CH2:9][CH2:10][CH3:11])[CH:1]=[O:4]
Reactant: CCCC(C)C=O
Reactant: CCC=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCC(C)C=C(C)C=O

Procedure:
In a similar manner as Example 1, this example is a cross-aldol condensation reaction (Aldol II) of propanal and 2-methyl-pentanal in a sodium hydroxide/water medium to form the 2,4-dimethyl-2-heptenal product that shows the productivity and selectivity results in a conventional system. The 2-methyl-pentanal starting material (175 mmol, 17.5 g) and nonane (internal standard) (8.7 mmol, 1.12 g) were added to a water solution of sodium hydroxide (1 M) (8.8 mmol, 0.352 g). The resulting mixture was heated to 90° C. and treated with propanal starting material (44.8 mmol, 2.6 g). After the addition, the reaction mixture was refluxed for an additional 3 hours at 90° C. The resulting solution turned a light yellow color and was further investigated using GC and GC/MS techniques. Catalyst evaluation results are presented in the bottom row of Table 2.
Reaction SMILES: C1(P(O[C:16]2[C@H:17]([CH3:40])[C@@H:18]3[C@@H:35]([C@H:36]([OH:38])[CH3:37])[C:34](=[O:39])[N:19]3[C:20]=2[C:21]([O:23]CC2C=CC([N+]([O-])=O)=CC=2)=[O:22])(C2C=CC=CC=2)=O)C=CC=CC=1.[SH:41][C@@H:42]1[CH2:46][N:45]([CH3:47])[C@H:44]([C:48]([N:50]2[CH2:53][CH:52]([N:54](C(OCC3C=CC([N+]([O-])=O)=CC=3)=O)[CH:55]=[NH:56])[CH2:51]2)=[O:49])[CH2:43]1>>[CH:55]([NH:54][CH:52]1[CH2:51][N:50]([C:48]([C@@H:44]2[CH2:43][C@H:42]([S:41][C:16]3[C@H:17]([CH3:40])[C@@H:18]4[C@@H:35]([C@H:36]([OH:38])[CH3:37])[C:34](=[O:39])[N:19]4[C:20]=3[C:21]([OH:23])=[O:22])[CH2:46][N:45]2[CH3:47])=[O:49])[CH2:53]1)=[NH:56]
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(OP(=O)(c3ccccc3)c3ccccc3)[C@H](C)[C@H]12
Reactant: CN1C[C@@H](S)C[C@H]1C(=O)N1CC(N(C=N)C(=O)OCc2ccc([N+](=O)[O-])cc2)C1
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(S[C@H]3C[C@@H](C(=O)N4CC(NC=N)C4)N(C)C3)[C@H](C)[C@H]12
Yield: 7.2 %

Procedure:
A procedure similar to that described in Example 125 was repeated, but using 0.35 g of 4-nitrobenzyl (1R,5R,6S)-2-(diphenylphosphoryloxy)-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (prepared as described in Preparation 123) and 0.22 g of (2S,4S)-4-mercapto-1-methyl-2-{3-[N-(4-nitrobenzyloxycarbonyl)-N-formimidoylamino]azetidin-1-ylcarbonyl}pyrrolidine (prepared as described in Preparation 118), to give 17 mg of the title compound as a powder.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[CH:6]=1)=[O:4].[S-:15][C:16]#[N:17].[K+]>C(O)C>[S:15]([CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[CH:6]=1)=[O:4])[C:16]#[N:17]
Reactant: O=C(CBr)c1cccc(C(F)(F)F)c1
Reactant: N#C[S-]
Agent: [K+]
Solvent: CCO
Product: N#CSCC(=O)c1cccc(C(F)(F)F)c1
Yield: 98 %

Procedure:
A mixture of 10.17 g (36.83 mmole) of 2-bromo-1-(3-trifluoromethyl-phenyl)-ethanone, 4.07 g (41.98 mmole) of potassium thiocyanate and ethanol was heated at reflux for 2 hours. The cooled mixture was concentrated under reduced pressure. The residue was taken up in 225 mL of ethyl acetate, washed three times with 50 mL of water, then 50 mL of brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 8.85 g of 2-thiocyanato-1-(3-trifluoromethyl-phenyl)-ethanone.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:18]([NH:26][C:27]1[CH:36]=[C:35](Br)[CH:34]=[CH:33][C:28]=1[C:29]([O:31]C)=[O:30])(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C)C(=O)C>[C:18]([NH:26][C:27]1[CH:36]=[C:35]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=2)[CH:34]=[CH:33][C:28]=1[C:29]([OH:31])=[O:30])(=[O:25])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: COC(=O)c1ccc(Br)cc1NC(=O)c1ccccc1
Reactant: COc1cccc(B(O)O)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: COc1cccc(-c2ccc(C(=O)O)c(NC(=O)c3ccccc3)c2)c1
Temperature: 90 °C
Reaction time: 11 h
Yield: 24.7 %

Procedure:
36 mg of 3-methoxyphenylboronic acid, 55 mg of sodium carbonate and 30 mg polymer supported bis(acetato)triphenylphosphine palladium(II) were added to 2.5 mL of N,N-dimethylacetamide solution containing 70 mg of methyl 2-(benzamido)-4-bromobenzoate, and stirred at 90° C. for 11 hours. After the reaction mixture was cooled to room temperature, insoluble were removed by filtration and ethyl acetate and 1.2 mol/L hydrochloric acid were added. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with 1.0 mol/L hydrochloric acid, a saturated sodium hydrogen carbonate aqueous solution and a saturated sodium chloride aqueous solution sequentially, and one solvent was evaporated under reduced pressure, 1.0 mL of 1.0 mol/L aqueous sodium hydroxide and 2.0 mL of ethanol were added to the obtained residue and stirred at room temperature for 1 hour. 0.6 mol/L hydrochloric acid was added to the reaction mixture and a solid substance was separated by filtration to obtain 18 mg of 2-(benzamido)-4-(3-methoxyphenyl)benzoic acid as white solid.
Reaction SMILES: C([O:4][C:5]1[C:6](=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:7](Cl)=[O:8])(=O)C.Cl.[CH3:15][N:16]([CH3:18])[OH:17].C(N(CC)CC)C>C(Cl)Cl>[CH3:15][N:16]([O:17][C:7]([C:6]1[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=1[OH:4])=[O:8])[CH3:18]
Reactant: CC(=O)Oc1ccccc1C(=O)Cl
Reactant: CN(C)O
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN(C)OC(=O)c1ccccc1O
Temperature: 25 °C
Reaction time: 6 h

Procedure:
6.00 Grams of acetylsalicylic acid chloride was dissolved in 70 ml of methylene chloride, and 7.37 g of N,N-dimethylhydroxylamine hydrochloride was added. Then, 9.16 of triethylamine was added dropwise thereto with stirring at room temperature. After completion of addition, stirring was carried out at room temperature for further 6 hours. The reaction mixture was washed with a 0.5N hydrochloric acid and then twice with water, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue obtained was subjected to column chromatography to obtain 3.10 g of 2-(N,N-dimethylaminooxycarbonyl)phenol.
Reaction SMILES: [NH2:1][C:2]1[C:3]([CH2:8][C:9]([O:11]CC)=O)=[N:4][CH:5]=[CH:6][CH:7]=1.Cl>C(OCC)C>[NH:1]1[C:2]2[C:3](=[N:4][CH:5]=[CH:6][CH:7]=2)[CH2:8][C:9]1=[O:11]
Reactant: CCOC(=O)Cc1ncccc1N
Agent: Cl
Solvent: CCOCC
Product: O=C1Cc2ncccc2N1
Reaction time: 0.5 h
Yield: 78.5 %

Procedure:
Ethyl 2-(3-amino-pyridin-2-yl)-acetate (6.94 g, 0.038 mol) was dissolved in diethyl ether (100 mL) at room temperature. Hydrochloric acid (2M, 35 mL) was added, and the reaction was stirred for 30 minutes. The volatiles were removed to afford a brown solid that was recrystallized from ethanol and diethyl ether to provide the title compound (4.0 g, 62% yield). 1H NMR 400 MHz (DMSO-d6): δ 12.35 (s, 1H); 8.12 (m, 1H); 7.90 (m, 1H); 7.14 (m, 1H); 5.75 (s, 2H). Electrospray MS m/z 135 (M+H).
Reaction SMILES: [CH2:1]=[CH:2][CH2:3]/[CH:4]=[CH:5]\[CH2:6]/[CH:7]=[CH:8]\[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]1[CH:21]=[C:20]([OH:22])[CH:19]=[CH:18][CH:17]=1.C(OCC)(=O)C>[Ni].[Pt]=O.CO>[CH2:15]([C:16]1[CH:21]=[C:20]([OH:22])[CH:19]=[CH:18][CH:17]=1)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:1]
Reactant: C=CC/C=C\C/C=C\CCCCCCCc1cccc(O)c1
Agent: O=[Pt]
Agent: [Ni]
Solvent: CO
Solvent: CCOC(C)=O
Product: CCCCCCCCCCCCCCCc1cccc(O)c1
Reaction time: 3 h

Procedure:
100 g of cardanol in solvents (100 cm3) such as ethyl acetate, methanol and the like was hydrogenated in a parr hydrogenator at 30-60 psi pressure by using catalysts (50 mg) such as palladised carbon, platinum oxide, raney nickel and the like. at 30-100° C. The hydrogenation was carried out for 2-4 hrs. The solution was filtered to remove the catalyst and methanol stripped off. The crude 3-pentadecyl phenol was distilled under vacuum (4 mm of Hg). The fraction which distilled at 200° C. to 210° C. was collected. The white solid obtained was recrystallised from hexane twice to obtain pure 3-pentadecyl phenol.
Reaction SMILES: [CH:1]1([C:7](=[NH:9])[NH2:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[Cl:19][C:20]([SH:23])(Cl)Cl>C(Cl)Cl>[Cl:19][C:20]1[S:23][N:8]=[C:7]([CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[N:9]=1
Reactant: N=C(N)C1CCCCC1
Reactant: SC(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Clc1nc(C2CCCCC2)ns1
Temperature: 2.5 °C
Reaction time: 1 h

Procedure:
Cyclohexanecarboximidamide (100 mg, 792 μmol) and DIPEA (512 mg, 3.96 mmol) in 10 mL DCM at 0-5° C. were treated with perchloromethyl mercaptan (147 mg, 792 μmol) in 5 mL DCM and stirred for 1 hr at 0-5° C. The mixture was concentrated in vacuo to give a brown solid which was used with out further purification in the subsequent step.
Reaction SMILES: Cl.C([N:9]([CH2:23][C@H:24]([OH:33])[CH2:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH:10]1[CH2:16][CH2:15][CH2:14][C:13]2[CH:17]=[C:18]([OH:22])[C:19]([Cl:21])=[CH:20][C:12]=2[CH2:11]1)C1C=CC=CC=1.[H][H]>ClC1C=CC=CC=1.CO.[Pd]>[ClH:21].[Cl:21][C:19]1[C:18]([OH:22])=[CH:17][C:13]2[CH2:14][CH2:15][CH2:16][CH:10]([NH:9][CH2:23][C@H:24]([OH:33])[CH2:25][O:26][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:11][C:12]=2[CH:20]=1
Reactant: Oc1cc2c(cc1Cl)CC(N(Cc1ccccc1)C[C@H](O)COc1ccccc1)CCC2
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: Clc1ccccc1
Solvent: CO
Product: Oc1cc2c(cc1Cl)CC(NC[C@H](O)COc1ccccc1)CCC2
Yield: 150 %

Procedure:
A mixture of (2S)-1-[N-benzyl-N-(3-chloro-6,7,8,9-tetrahydro-2-hydroxy-5H-benzocyclohepten-6-yl)amino]-3-phenoxy-2-propanol hydrochloride (121 mg) and 10% Pd/C (50% wet, 18 mg) in chlorobenzene (1.8 ml) and MeOH (0.4 ml) was stirred at room temperature in the presence of hydrogen at an atmospheric pressure for 1 hour and filtered. The filtrate was evaporated in vacuo, and the residue was partitioned between ethyl acetate and a saturated aqueous solution of sodium bicarbonate. The organic layer was separated, washed with brine, dried over sodium sulfate and evaporated in vacuo. The residue was chromatographed (dichloromethane-methanol) over silica gel (2.0 g). The eluate was treated with 4N hydrogen chloride in ethyl acetate and evaporated in vacuo. The residue was triturated in diisopropyl ether, and the precipitated powder was collected by filtration to afford (2S)-1-(3-chloro-6,7,8,9-tetrahydro-2-hydroxy-5H-benzocyclohepten-6-yl)amino-3-phenoxy-2-propanol hydrochloride (74 mg, 75%) as a colorless powder.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]=O)[CH:2]=1.[BH4-].[Na+].[CH3:11][NH2:12]>CO>[CH3:11][NH:12][CH2:7][C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1
Reactant: CN
Reactant: O=Cc1cccnc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CNCc1cccnc1
Temperature: 25 °C
Reaction time: 23 h

Procedure:
To a solution of 3-pyridine-carboxaldehyde (0.24 g) in methanol, methylamine (2.0 M solution in tetrahydrofuran, 6 ml) was added, and the mixture was stirred at room temperature for 23 hours. Then, sodium borohydride (0.22 g) was added thereto, and the mixture was stirred for 1 hour. The reaction solution was concentrated under reduced pressure. The residue was partially purified on a reverse-phase silica gel column. A crude product was obtained by decantation and directly used in the next reaction.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]2[C:13](=[O:14])[CH:12]3[CH2:15][C:10]([C:16]4[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][CH:17]=4)([CH2:11]3)[C:9]2=[O:25])=[CH:5][CH:4]=1.CCOCC>C(OCC)(=O)C.[Pd]>[NH2:22][C:19]1[CH:20]=[CH:21][C:16]([C:10]23[CH2:11][CH:12]([CH2:15]2)[C:13](=[O:14])[N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:27][CH:26]=2)[C:9]3=[O:25])=[CH:17][CH:18]=1
Reactant: COc1ccc(CN2C(=O)C3CC(c4ccc([N+](=O)[O-])cc4)(C3)C2=O)cc1
Agent: [Pd]
Solvent: CCOCC
Solvent: CCOC(C)=O
Product: COc1ccc(CN2C(=O)C3CC(c4ccc(N)cc4)(C3)C2=O)cc1

Procedure:
In a manner analogous to that described in Example 1a, 5.0 g of 3-(4-methoxybenzyl)-1-(4-nitrophenyl)-3-azabicyclo[3.1.1]heptane-2,4-dione are dissolved in 100 ml of ethyl acetate, hydrogenated in the presence of 1 g of 5% palladium-on-carbon and worked up. Melting point 147°-147.5° (from ether).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:20]2[C:19]3[CH:18]=[CH:17][CH:16]=[C:15]([O:21][CH2:22][C:23]([F:29])([F:28])[C:24]([F:27])([F:26])[F:25])[C:14]=3[N:13]=[C:12](Cl)[C:11]=2[CH2:10][CH2:9]1.[NH2:31][CH2:32][CH2:33][CH2:34][OH:35]>>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:20]2[C:19]3[CH:18]=[CH:17][CH:16]=[C:15]([O:21][CH2:22][C:23]([F:29])([F:28])[C:24]([F:27])([F:26])[F:25])[C:14]=3[N:13]=[C:12]([NH:31][CH2:32][CH2:33][CH2:34][OH:35])[C:11]=2[CH2:10][CH2:9]1
Reactant: Cc1ccccc1N1CCc2c(Cl)nc3c(OCC(F)(F)C(F)(F)F)cccc3c21
Reactant: NCCCO
Product: Cc1ccccc1N1CCc2c(NCCCO)nc3c(OCC(F)(F)C(F)(F)F)cccc3c21

Procedure:
1-(2-Methylphenyl)-4-chloro-6-β,β,γ,γ,γ-pentafluoropropyloxy-2,3-dihydropyrrolo[3,2-c]quinoline(570 mg, 1.2 mmol) was dissolved in 3-amino-1-propanol(5.0 ml), and reacted at the same condition of Step 6 in the Example 57 to obtain 260 mg of desired compound as solid in 42% of yield.