Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([OH:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Cl[C:11]1[N:15]([CH3:16])[N:14]=[C:13]([CH3:17])[C:12]=1[CH:18]=[O:19]>CN(C)C=O>[CH3:16][N:15]1[C:11]([O:7][CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[C:12]([CH:18]=[O:19])[C:13]([CH3:17])=[N:14]1
Reactant: Cc1nn(C)c(Cl)c1C=O
Reactant: OC1CCCCC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1nn(C)c(OC2CCCCC2)c1C=O
Temperature: 0 °C
Reaction time: 1 h
Yield: 4.3 %

Procedure:
Under a nitrogen gas atmosphere, 3.48 g (0.0347 mole) of cyclohexanol was added at 0° C. to 50 ml of an N,N-dimethylformamide solution containing 1.45 g (0.03625 mole) of suspended sodium hydride. The resulting mixture was stirred at 0° C. for 1 hour. Thereafter, a solution of 5 g (0.0315 mole) of 5-chloro-1,3-dimethyl-4-formylpyrazole in 20 ml of N,N-dimethylformamide was added dropwise at 20° C. over 1 hour. The reaction mixture was stirred at 20° C. for 5 hours. The reaction mixture was then poured into 300 ml of ice water and extracted with two 100-ml portions of ethyl acetate. The organic layers were combined, washed once with 100 ml of a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, then concentrated under reduced pressure. The residue was subjected to column chromatography on silica gel to obtain 0.3 g of 1,3-dimethyl-5-cyclohexyloxy-4-formylpyrazole.
Reaction SMILES: [OH:1][C:2]([C:27]([F:30])([F:29])[F:28])([CH3:26])[CH:3]=[CH:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[C:8]2[CH2:14][C@H:15]1[CH2:19][CH2:18][CH2:17][N:16]1[CH2:20][CH2:21][C:22](=[O:25])[NH:23][CH3:24].CO.C(Cl)Cl>[Pd].O>[OH:1][C:2]([C:27]([F:29])([F:30])[F:28])([CH3:26])[CH2:3][CH2:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[C:8]2[CH2:14][C@H:15]1[CH2:19][CH2:18][CH2:17][N:16]1[CH2:20][CH2:21][C:22](=[O:25])[NH:23][CH3:24]
Reactant: CNC(=O)CCN1CCC[C@@H]1Cc1c[nH]c2ccc(C=CC(C)(O)C(F)(F)F)cc12
Agent: [Pd]
Solvent: ClCCl
Solvent: CO
Solvent: O
Product: CNC(=O)CCN1CCC[C@@H]1Cc1c[nH]c2ccc(CCC(C)(O)C(F)(F)F)cc12

Procedure:
Obtained from the title compound of Example 98 by a procedure similar to that described in Example 2, but using 10% palladium on charcoal as catalyst, as a foam. Rf 0.45 (SS 7). [α]D25 +39° (c=0.1, CH3OH). Found: C,59.07; H,7.16; N,9.21. C22H30F3N3O2 ; 0.05 CH2Cl2 ; H2O requires C,59.15; H,7.22; N,9.39%. LRMS: m/z 426.4 (M+1)+.
Reaction SMILES: [C:1]([C:3]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:4]=1[CH2:5][N:6]1[C:11](=[O:12])[C:10]([CH3:13])=[N:9][N:8]=[C:7]1[N:14]1[CH2:19][CH2:18][CH2:17][C@@H:16]([NH:20]C(=O)OC(C)(C)C)[CH2:15]1)#[N:2].C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>ClCCl>[NH2:20][C@@H:16]1[CH2:17][CH2:18][CH2:19][N:14]([C:7]2[N:6]([CH2:5][C:4]3[CH:28]=[C:29]([F:32])[CH:30]=[CH:31][C:3]=3[C:1]#[N:2])[C:11](=[O:12])[C:10]([CH3:13])=[N:9][N:8]=2)[CH2:15]1
Reactant: Cc1nnc(N2CCC[C@@H](NC(=O)OC(C)(C)C)C2)n(Cc2cc(F)ccc2C#N)c1=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1nnc(N2CCC[C@@H](N)C2)n(Cc2cc(F)ccc2C#N)c1=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of (R)-tert-butyl 1-(4-(2-cyano-5-fluorobenzyl)-6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)piperidin-3-ylcarbamate (20, 37 mg) in dichloromethane (1 mL) was added TFA (0.5 mL) and the mixture was stirred at RT for 1 h. The mixture was carefully neutralized with NaHCO3 (aq, saturated), and extracted with CH2Cl2 (10 mL×3). The combined extracts were dried over Na2SO4 and concentrated to give the crude product, which was purified by column chromatography on silica gel, and eluted with 92:6:2 dichloromethane-methanol-ammonia to provide (R)-2-((3-(3-aminopiperidin-1-yl)-6-methyl-5-oxo-1,2,4-triazin-4(5H)-yl)methyl)-4-fluorobenzonitrile (21). 1H NMR (400 MHz, DMSO, ppm): δ 7.96 (m, 1H), 7.36 (br, 1H), 7.29 (d, 1H), 5.23 (s, 2H), 3.15 (m, 3H), 2.72 (m, 2H), 2.23 (s, 3H), 1.78 (d, 1H), 1.64 (d, 1H), 1.47 (m, 1H), 1.12 (m, 1H). MS: m/z, 343 (100%, M+1);
Reaction SMILES: [NH2:1][C:2]1[O:3][CH2:4][C@:5]2([N:21]=1)[C:18]1[CH:17]=[C:16](Br)[CH:15]=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([OH:20])=[CH:9][CH:10]=1.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24](B(O)O)[CH:23]=1.C1COCC1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([N:21]=1)[C:6]1[CH:7]=[C:8]([OH:20])[CH:9]=[CH:10][C:11]=1[O:12][C:13]1[C:18]2=[CH:17][C:16]([C:24]2[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=2)=[CH:15][CH:14]=1
Reactant: OB(O)c1cccnc1
Reactant: NC1=N[C@]2(CO1)c1cc(O)ccc1Oc1ccc(Br)cc12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: ClCCl
Product: NC1=N[C@]2(CO1)c1cc(O)ccc1Oc1ccc(-c3cccnc3)cc12

Procedure:
A 75-mL pressure vessel was charged with (R)-2-amino-2′-bromo-5H-spiro[oxazole-4,9′-xanthen]-7′-ol (3.25 g, 9.36 mmol), pyridin-3-ylboronic acid (2.88 g, 23.40 mmol), tetrakis(triphenylphosphine)palladium(0) (1.081 g, 0.936 mmol), THF (46.8 mL), and potassium carbonate (23.40 mL, 46.8 mmol) (as a 2.0 M aq. solution). The vessel was sealed and placed in a 100° C. oil bath for 6 hours. The mixture was partitioned between EtOAc (50 mL) and water (50 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (2×30 mL. The combined mixture was dried over sodium sulfate and filtered with the aid of 10% MeOH/CH2Cl2. The filtrate was evaporated to give a yellow solid. This solid was taken up in CH2Cl2 (80 mL) and sonicated for 5 min. The solid was filtered and washed with CH2Cl2 (2×40 mL), then air-dried on the filter. The filtrate was evaporated and again taken up in CH2Cl2 (80 mL). The mixture was sonicated for 10 min, then filtered and washed with CH2Cl2 (30 mL). The solid was air-dried and combined with the first solid to give (S)-2-amino-7′-(pyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2′-ol. MS m/z=346.0 [M+H].
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12](O)=O.[CH2:15]([SH:25])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24].C[O-:27].[Na+]>CO>[CH2:3]([CH2:2][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][C:15]([OH:27])=[S:25])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCS
Reactant: C[O-]
Reactant: O=C(O)CCCCCCCCCCBr
Agent: [Na+]
Solvent: CO
Product: CCCCCCCCCCCCCCCCCCCCC(O)=S
Temperature: 25 °C
Yield: 82.4 %

Procedure:
In a 3000 ml flask equipped with a stirrer and a condenser were charged 132 g of 11-bromoundecanoic acid, 91.5 g of n-decanthiol, 59.4 g of sodium methoxide (28% methanol solution) and 1500 ml of methanol, and the mixture was refluxed for 12 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, precipitated crystals were collected by filtration under reduced pressure and the resulting crystals were washed with methanol. The resulting crystals were suspended in 5000 ml of distilled water, and the suspension was neutralized by a conc. hydrochloric acid, and the crystals were again collected by filtration under reduced pressure. The crystals were washed with water until the washed solution became neutral, and recrystallized from ethanol to obtain 140.5 g of the title compound.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:20][C:21]1[CH:22]=[C:23]([CH:43]=[CH:44][CH:45]=1)[C:24]([NH:26][C:27]1[C:28]([N:34]2[CH2:39][CH2:38][CH:37]([CH2:40][CH2:41]O)[CH2:36][CH2:35]2)=[N:29][CH:30]=[C:31]([Cl:33])[CH:32]=1)=[O:25].C(Cl)(Cl)(Cl)[Cl:47]>>[Cl:20][C:21]1[CH:22]=[C:23]([CH:43]=[CH:44][CH:45]=1)[C:24]([NH:26][C:27]1[C:28]([N:34]2[CH2:39][CH2:38][CH:37]([CH2:40][CH2:41][Cl:47])[CH2:36][CH2:35]2)=[N:29][CH:30]=[C:31]([Cl:33])[CH:32]=1)=[O:25]
Reactant: O=C(Nc1cc(Cl)cnc1N1CCC(CCO)CC1)c1cccc(Cl)c1
Reactant: ClC(Cl)(Cl)Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: O=C(Nc1cc(Cl)cnc1N1CCC(CCCl)CC1)c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 30 %

Procedure:
A mixture of 0.76 g (10 mmol) of triphenylphosphine and 1.97 g (5.00 mmol) of the above amide in carbon tetrachloride (50 mL) is stirred overnight at room temperature. The solvent is concentrated, and the residue is purified by flash silica gel chromatography to provide 1.24 g (30%) of 3-chloro-N-[5′-chloro-4-(2-chloro-ethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-3′-yl]-benzamide as a white solid.
Reaction SMILES: C([O:3][P:4]([CH2:9][CH2:10][C@@:11]1([NH:30]C(=O)OC(C)(C)C)[CH2:15][CH2:14][C@H:13]([C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])=[CH:18][CH:17]=2)[CH2:12]1)([O:6]CC)=[O:5])C.Br[Si](C)(C)C.O.CCCCC>ClCCl>[NH2:30][C@:11]1([CH2:10][CH2:9][P:4](=[O:3])([OH:6])[OH:5])[CH2:15][CH2:14][C@H:13]([C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])=[CH:18][CH:17]=2)[CH2:12]1
Reactant: CCCCCCCCc1ccc([C@H]2CC[C@@](CCP(=O)(OCC)OCC)(NC(=O)OC(C)(C)C)C2)cc1
Agent: C[Si](C)(C)Br
Solvent: CCCCC
Solvent: ClCCl
Solvent: O
Product: CCCCCCCCc1ccc([C@H]2CC[C@](N)(CCP(=O)(O)O)C2)cc1
Reaction time: 4 h
Yield: 89.5 %

Procedure:
Tert-butyl (1R,3S)-1-(2-(diethoxyphosphoryl)ethyl)-3-(4-octylphenyl)cyclopentylcarbamate (0.236 g, 0.439 mmol) was dissolved in dichloromethane (4.39 ml) under nitrogen to give a colorless solution. Bromotrimethylsilane (0.569 ml, 4.39 mmol) (Aldrich) was added and the reaction stirred for about 4 h. Solvents were removed under reduced pressure. Methanol (4 mL) and water (0.2 mL) were added and the solution was stirred for about 16 h. Solvents were removed under reduced pressure to give a brown oil/solid. Water was added and the solution sonicated while scraping the sides of the vial. The solution was stirred with a stir bar for about 1 h. The resulting solid was collected by vacuum filtration and washed with water and then pentane to provide 2-((1R,3S)-1-amino-3-(4-octylphenyl)cyclopentyl)ethylphosphonic acid (0.150 g, 0.393 mmol, 90% yield) as a off-white solid on drying under vacuum at 60° C.: LC/MS (method a) Rt=3.15 min.; MS m/z: 382.27 (M+H)+.
Reaction SMILES: [CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[O:25])=[CH:20][N:19]=2)[C:3]1=[O:32].Br[C:34]1[C:35]([CH3:54])=[C:36]([N:40]2[CH2:49][CH2:48][C:47]3[C:42](=[CH:43][CH:44]=[C:45]([N:50]([CH3:52])[CH3:51])[CH:46]=3)[C:41]2=[O:53])[CH:37]=[CH:38][CH:39]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[CH3:51][N:50]([CH3:52])[C:45]1[CH:46]=[C:47]2[C:42](=[CH:43][CH:44]=1)[C:41](=[O:53])[N:40]([C:36]1[CH:37]=[CH:38][CH:39]=[C:34]([C:6]3[CH:5]=[C:4]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([C:24]([N:26]5[CH2:27][CH2:28][O:29][CH2:30][CH2:31]5)=[O:25])=[CH:20][N:19]=4)[C:3](=[O:32])[N:2]([CH3:1])[CH:7]=3)[C:35]=1[CH3:54])[CH2:49][CH2:48]2
Reactant: Cc1c(Br)cccc1N1CCc2cc(N(C)C)ccc2C1=O
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cc(Nc2ccc(C(=O)N3CCOCC3)cn2)c1=O
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Product: Cc1c(-c2cc(Nc3ccc(C(=O)N4CCOCC4)cn3)c(=O)n(C)c2)cccc1N1CCc2cc(N(C)C)ccc2C1=O
Temperature: 100 °C
Yield: 31.1 %

Procedure:
To 1-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one (77 mg, 0.18 mmol), 2-(3-Bromo-2-methyl-phenyl)-6-dimethylamino-3,4-dihydro-2H-isoquinolin-1-one (63 mg, 0.18 mmol), potassium phosphate (74 mg, 0.35 mmol), 2-(dicyclohexylphoshphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (5.0 mg, 0.010 mmol), and bis(dibenzylidineacetone)palladium(0) (3.0 mg, 0.0052 mmol) was added 4 mL of degassed 1:3 water/n-butanol. The headspace of the vessel was evacuated and backfilled with argon 4 times. This was heated at 100° C. for 110 minutes. This was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by flash chromatography (gradient elution 2 to 5% methanol/dichloromethane) to yield 6-Dimethylamino-2-(2-methyl-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-3,4-dihydro-2H-isoquinolin-1-one (33 mg, 0.056 mmol). MS (ESI) 593.3 (M+H)+.
Reaction SMILES: C[Mg]I.[CH2:4](N(CC)CC)C.C(O[C:14]([C:16]1[CH:20]=[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=2)[O:18][N:17]=1)=[O:15])C.Cl>C1(C)C=CC=CC=1>[F:30][C:27]([F:28])([F:29])[C:23]1[CH:22]=[C:21]([C:19]2[O:18][N:17]=[C:16]([C:14](=[O:15])[CH3:4])[CH:20]=2)[CH:26]=[CH:25][CH:24]=1
Reactant: CCN(CC)CC
Reactant: CCOC(=O)c1cc(-c2cccc(C(F)(F)F)c2)on1
Agent: C[Mg]I
Agent: Cl
Solvent: Cc1ccccc1
Product: CC(=O)c1cc(-c2cccc(C(F)(F)F)c2)on1
Temperature: 2.5 °C
Reaction time: 2 h
Yield: 37.9 %

Procedure:
To a cooled (5-10° C.) solution of 4.6 ml (0.014 mol) methyl magnesium iodide solution (3M in diethyl ether) and 5.8 ml (0.042 mol) triethylamine in 10 ml toluene, a solution of 2.06 g (0.00723 mol) 5-(3-trifluoromethyl-phenyl)-isoxazole-3-carboxylic acid ethyl ester in 20 ml toluene was added dropwise. After the addition was complete, the reaction mixture was stirred at 0-5° C. for 2 h and then treated with 5.6 ml 4N aqueous HCl solution. The mixture was filtered over celite. The aqueous phase was separated and the organic layer was washed with water, 5% aqueous NaHCO3 solution and twice with water. The organic phase was dried over magnesium sulfate and the solvent was evaporated. The residue was dissolved in a mixture of 28 ml MeOH and 0.45 ml 20% aqueous KOH solution. The solution was heated to 45° C. for 30 min, then cooled and acidified to pH 2 by addition of 6N HCl. The solvent was evaporated and the residue was mixed with toluene and aqueous NaHCO3 solution. The mixture was filtered over celite. The organic layer was separated and the solvent was evaporated to yield 0.7 g (0.00274 mol) 1-[5-(3-trifluoromethyl-phenyl)-isoxazol-3-yl]-ethanone.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][CH:14]([N:17]([C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][N:26]=2)[C:18]([C:20]2[O:21][CH:22]=[CH:23][CH:24]=2)=[O:19])[CH2:13][CH2:12]1.[CH:32]1([CH:38](C)[C:39](O)=[O:40])CCCCC1.ON1[C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=2N=N1.Cl.C(N=C=NCCCN(C)C)C>ClCCl.C(Cl)(Cl)Cl>[CH:47]1([CH2:32][CH2:38][C:39]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[CH2:8][CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([N:17]([C:25]3[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][N:26]=3)[C:18]([C:20]3[O:21][CH:22]=[CH:23][CH:24]=3)=[O:19])[CH2:13][CH2:12]2)=[O:40])[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1
Reactant: CC(C(=O)O)C1CCCCC1
Reactant: On1nnc2ccccc21
Reactant: Cc1ccc(N(C(=O)c2ccco2)C2CCN(CCCc3ccccc3N)CC2)nc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: Cc1ccc(N(C(=O)c2ccco2)C2CCN(CCCc3ccccc3NC(=O)CCC3CCCCC3)CC2)nc1
Temperature: 25 °C
Reaction time: 64 h
Yield: 90.2 %

Procedure:
To a solution of N-[1-[3-(2-aminophenyl)propyl]piperidin-4-yl]-N-(5-methylpyridin-2-yl)-2-furancarboxamide (100 mg) and cyclohexylpropionic acid (49 mg) in dichloromethane (3 mL) were added 1-hydroxybenzotriazole (42 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (60 mg) under ice cooling. The solution was stirred at room temperature for 64 hours. Chloroform was then added to the solution and the solution was washed in turn with water and saturated aqueous sodium bicarbonate solution. The solution was dried over anhydrous sodium sulfate, and then, concentrated under reduced pressure. The residue was purified by chromatography (NH silica gel, hexane:ethyl acetate=1:2) to give the title compound (120 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.[N:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH:18]=O>N1CCCCC1.C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[CH:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][N:12]=1
Reactant: O=C1Cc2cc(Cl)ccc2N1
Reactant: O=Cc1ccccn1
Solvent: C1CCNCC1
Solvent: CCO
Product: O=C1Nc2ccc(Cl)cc2C1=Cc1ccccn1
Temperature: 80 °C
Reaction time: 6 h

Procedure:
A 5 mL of ethanol solution containing 5-chlorooxindole (167 mg, 1 mmol), 2-pyridine-carboxaldehyde (129 mg, 1.2 mmol) and 3 drops of piperidine was stirred at 80° C. for 6 hours. After cooling the solution to 5° C., yellow precipitate was obtained (200 mg, 78%). MS: m/z 257 [M+1]+.
Reaction SMILES: [C:1]([Cl:4])(Cl)=[O:2].C([N:12]1[CH2:16][CH2:15][CH:14]([O:17][C:18]2[CH:23]=[C:22]([Cl:24])[CH:21]=[C:20]([Cl:25])[CH:19]=2)[CH2:13]1)C1C=CC=CC=1>C1C=CC=CC=1>[Cl:24][C:22]1[CH:23]=[C:18]([CH:19]=[C:20]([Cl:25])[CH:21]=1)[O:17][CH:14]1[CH2:15][CH2:16][N:12]([C:1]([Cl:4])=[O:2])[CH2:13]1
Reactant: O=C(Cl)Cl
Reactant: Clc1cc(Cl)cc(OC2CCN(Cc3ccccc3)C2)c1
Solvent: c1ccccc1
Product: O=C(Cl)N1CCC(Oc2cc(Cl)cc(Cl)c2)C1
Temperature: 5 °C

Procedure:
To a stirred solution of 200 ml of 2 molar phosgene in benzene under nitrogen gas was added dropwise over a 3 hr period, a solution of 115 g (0.358 mole) of 1-benzyl-3-(3,5-dichlorophenoxy)pyrrolidine in 100 ml of benzene. The resulting solution was concentrated on a rotary evaporator to give an oil. The oil was triturated three times with boiling 30/60 petroleum ether, decanting each time. The oil residue solidified on cooling. The solid was taken up in benzene and the solution filtered, charcoaled and filtered. Crystalline product was obtained by adding ligroin and cooling to 5° C. in the amount of 92.7 g (87.9%), m.p. 105°-107° C. A purer 3 g sample, m.p. 106°-108° C. was obtained from the petroleum ether on standing.
Reaction SMILES: Cl.[Cl:2][CH2:3][CH2:4][CH2:5][C:6]#[C:7][C:8]([NH2:11])([CH3:10])[CH3:9].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[Cl:34][C:35]1[CH:36]=[C:37]([CH:45]=[C:46]([Cl:48])[CH:47]=1)[O:38][CH:39]([CH2:43][CH3:44])[C:40](O)=[O:41]>CN(C)C=O.O.C(N(CC)CC)C>[Cl:34][C:35]1[CH:36]=[C:37]([CH:45]=[C:46]([Cl:48])[CH:47]=1)[O:38][CH:39]([CH2:43][CH3:44])[C:40]([NH:11][C:8]([CH3:10])([CH3:9])[C:7]#[C:6][CH2:5][CH2:4][CH2:3][Cl:2])=[O:41]
Reactant: CC(C)(N)C#CCCCCl
Reactant: CCC(Oc1cc(Cl)cc(Cl)c1)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: CCC(Oc1cc(Cl)cc(Cl)c1)C(=O)NC(C)(C)C#CCCCCl
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 97.8 %

Procedure:
1-Chloro-6-methylhept-4-yn-6-yl amine hydrochloride (9.8 g) in N,N-dimethylformamide (250 ml) containing triethylamine (10.4 ml) was stirred at ambient temperature for 10 minutes. The suspension which had formed was treated sequentially with 1-hydroxybenzotriazole (7.59 g), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (10.56 g) then 2-(3,5-dichlorophenoxy)-butyric acid (13.07 g) in N,N-dimethylformamide (50 ml). The mixture was stirred at ambient temperature for 2 hours, stored for 18 hours then poured into water. The product was extracted with ethyl acetate (three times). The extracts were combined, washed with a saturated aqueous solution of sodium hydrogen carbonate and water (three times) and dried over magnesium sulphate. They were then evaporated under reduced pressure to give the required product as a yellow gum (19.1 g) sufficiently pure for further derivatisation. A portion of the gum (0.33 g) was fractionated by chromatography (silica; hexane/diethyl ether, 4:1 by volume) to provide a pure sample of 2-(3,5-dichlorophenoxy)-N-(1-chloro-6-methylhept-4-yn-6-yl) butyramide as a colourless oil, 0.22 g, 1H NMR (CDCl3) δ: 1.00-1.04(3H, t); 1.58(6H, s); 1.90-2.00(4H, m); 2.36-2.40(2H, t); 3.62-3.66(2H, t); 4.36-4.40(1H, t); 6.26(1H, s); 6.84(2H, s); 7.02(1H, s).
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9](CO)[OH:10])[OH:8])[OH:6])[OH:4].[CH2:13]([OH:22])[C@@H:14]([OH:21])[CH:15]([OH:20])[C@H:16]([OH:19])[CH2:17][OH:18]>C(O)C>[OH:1][CH2:2][C:3]([C@H:5]([C@@H:7]([CH2:9][OH:10])[OH:8])[OH:6])=[O:4].[CH2:17]([OH:18])[C@@H:16]([C@H:15]([C@@H:14]([CH2:13][OH:22])[OH:21])[OH:20])[OH:19]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: OC[C@@H](O)C(O)[C@H](O)CO
Solvent: CCO
Product: O=C(CO)[C@@H](O)[C@H](O)CO
Product: OC[C@@H](O)[C@H](O)[C@@H](O)CO

Procedure:
Based on this idea, as shown in Example 6, glucose and ethanol were added and allowed to react in a conversion reaction of D-arabitol using Gluconobacter oxydans ATCC621 and the effect of their addition was examined. As a result, a considerable effect of addition was recognized as shown in Example 6. That is, when no carbon source was added, a portion of D-xylulose remained unreacted, giving a low yield of xylitol whereas with the addition of a carbon source, reduction of D-xylulose to xylitol proceeded advantageously and the yield of xylitol (based on the yield of D-arabitol) reached at most 98%.
Reaction SMILES: [C:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7])(=[O:3])[CH3:2].[CH:13]1([CH3:23])[CH2:18][CH2:17][CH:16]([CH:19]([CH3:21])[CH3:20])[CH:15](O)[CH2:14]1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.ClCCl>[C:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6]([O:8][C@H:15]1[C@H:16]([CH:19]([CH3:21])[CH3:20])[CH2:17][CH2:18][C@@H:13]([CH3:23])[CH2:14]1)=[O:7])(=[O:3])[CH3:2]
Reactant: CC(=O)c1ccccc1C(=O)O
Reactant: CC1CCC(C(C)C)C(O)C1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CC(=O)c1ccccc1C(=O)O[C@@H]1C[C@H](C)CC[C@H]1C(C)C
Reaction time: 70 h
Yield: 13 %

Procedure:
A solution of 11.36 g (50.0 mmol) 2-acetylbenzoic acid, 4.88 g (40.0 mmol) DMAP and 23.40 g (150.0 mmol) (−)-menthol in 80 ml dichloromethane was cooled in an ice bath before adding a solution of 11.36 g (55.0 mmol) DCC in 40 ml dichloromethane for 15 min. The reaction mixture was maintained with stirring at 40° for 70 h. The precipitate formed during the reaction was filtered and the filtrate washed with HCl (10%, 2×) then with a saturated Na2CO3 solution (2×). The organic phase was dried (Na2SO4), concentrated, chromatographed (SiO2, toluene) and recrystallized in hexane to give 1.96 g (13%) (1R,3R,4S)-3-p-menthanyl 2-acetylbenzoate in the form of white crystals.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[CH2:17]([O:24][C:25]1[CH:30]=[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:28]=[CH:27][C:26]=1[CH:39]1[CH2:42][NH:41][CH2:40]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O1CCCC1.C(N(CC)C(C)C)(C)C>[CH2:17]([O:24][C:25]1[CH:30]=[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:28]=[CH:27][C:26]=1[CH:39]1[CH2:42][N:41]([C:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:8])[CH2:40]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: c1ccc(COc2ccc(C3CNC3)c(OCc3ccccc3)c2)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: C1CCOC1
Product: O=C(c1ccccc1)N1CC(c2ccc(OCc3ccccc3)cc2OCc2ccccc2)C1
Temperature: 25 °C
Reaction time: 24 h
Yield: 82 %

Procedure:
In a 10 ml round-bottomed flask, 0.25 g of 3-(2,4-bis(benzyloxy)phenyl)azetidine trifluoroacetate in 5 ml of tetrahydrofuran is dissolved in the presence of 0.1 ml of N,N-diisopropylethylamine. 0.07 ml of benzoyl chloride is added and the mixture is then stirred for 24 hours at ambient temperature. The reaction mixture is extracted with ethyl acetate and the organic phases are then combined and dried over magnesium sulphate. The residue is chromatographed on silica gel (9/1 heptane/ethyl acetate). 0.2 g of [3-(2,4-bis(benzyloxy)phenyl)azetidin-1-yl]phenylmethanone is obtained. Yield=82%.