Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH:2]1[O:10][C@H:9]([CH2:11]O)[C@@H:7]([OH:8])[C@H:5]([OH:6])[C@@H:3]1[OH:4].C(O)C1C=CC=CC=1.CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[S:43](Cl)([C:46]1[CH:52]=[CH:51][C:49]([CH3:50])=[CH:48][CH:47]=1)(=[O:45])=[O:44]>C(Cl)Cl.CCOC(C)=O.CCOC(C)=O.CCCCCC>[S:43]([CH2:11][C@H:9]1[O:10][CH:2]([O:1][CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C@@H:3]([OH:4])[C@@H:5]([OH:6])[C@@H:7]1[OH:8])([C:46]1[CH:52]=[CH:51][C:49]([CH3:50])=[CH:48][CH:47]=1)(=[O:45])=[O:44]
Reactant: OC[C@H]1OC(OCc2ccccc2)[C@@H](O)[C@@H](O)[C@@H]1O
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Solvent: OCc1ccccc1
Solvent: ClCCl
Solvent: CCCCCC
Product: Cc1ccc(S(=O)(=O)C[C@H]2OC(OCc3ccccc3)[C@@H](O)[C@@H](O)[C@@H]2O)cc1
Reaction time: 4 h
Yield: 68 %

Procedure:
To a solution of benzyl mannopyranoside 18 (500 mg, 1.9 mmol; Synthesized via reflux in dry 1.0 Molar benzyl alcohol with 0.01 equivalents CSA, the reaction mixture is passed through a SiO2 column; benzyl alcohol comes out first using EtOAc:Hexane 1:5, then benzyl pyranoside is separated from the furanose byproduct with EtOAc as eluent) in dry pyridine (5 mL) at 0° C. was added tosyl chloride (381 mg, 2 mmol; Aldrich) dissolved in CH2Cl2 and the reaction was monitored by TLC (EtOAc). After 4 hours, the starting material was consumed completely. The reaction mixture was extracted with CH2Cl2 and washed with 1N HCl, sat. NaHCO3 and brine, and purified by flash chromatography using EtOAc as eluent to yield 531 mg (68%) of benzyl 6-tosyl-6-deoxy-D-mannopyranoside.
Reaction SMILES: [CH2:1]([O:13][C:14]1[CH:15]=[C:16]([C:33]2([CH:39]([C:41]3[CH:46]=[CH:45][C:44]([I:47])=[CH:43][CH:42]=3)[OH:40])SCCCS2)[CH:17]=[CH:18][C:19]=1[O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C1C(=O)N(Br)C(=[O:51])C1.[O-]S([O-])=O.[Na+].[Na+].C(Cl)Cl>CC(C)=O.O.CC(C)=O>[CH2:1]([O:13][C:14]1[CH:15]=[C:16]([C:33](=[O:51])[C:39]([C:41]2[CH:46]=[CH:45][C:44]([I:47])=[CH:43][CH:42]=2)=[O:40])[CH:17]=[CH:18][C:19]=1[O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCCCCCCCCCCCOc1ccc(C2(C(O)c3ccc(I)cc3)SCCCS2)cc1OCCCCCCCCCCCC
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(C)=O
Solvent: O
Product: CCCCCCCCCCCCOc1ccc(C(=O)C(=O)c2ccc(I)cc2)cc1OCCCCCCCCCCCC
Temperature: 12.5 °C
Reaction time: 0.5 h
Yield: 25.3 %

Procedure:
A solution of [2-(3,4-bis-dodecyloxy-phenyl)-[1,3]dithian-2-yl]-(4-iodo-phenyl)-methanol (JYC-II-020-A) (8.2 g, 10.3 mmol) in 400 mL of acetone was added dropwise to a solution of NBS (31.86 g, 17.9 mmol) in 3% water/acetone (v/v) at 0° C. The reaction mixture was stirred at 0-25° C. for 30 min. It was then poured into a saturated aqueous Na2SO3 solution (400 mL) and CH2Cl2 (400 mL) mixture. The resulting mixture was stirred at room temperature for additional 10 min. The organic layer was washed with H2O and dried over anhydrous MgSO4. The solvent was removed under reduced pressure. The crude product was recrystallized from hexanes. The product was further purified by column chromatography (silica gel, hexanes:dichloromethane=2:1 (v/v)) to give a light yellow solid (1.84 g, 25.4%). 1H NMR (300 MHz, CDCl3, δ): 7.85 (d, J=8.5 Hz, 2H), 7.65 (d, J=8.5 Hz, 2H), 7.53 (d, J=1.9 Hz, 1H), 7.38 (dd, J=8.5 Hz, 1.9 Hz, 1H), 6.83 (d, J=8.2 Hz, 1H), 4.04 (t, J=6.6 Hz, 2H), 4.03 (t, J=6.6 Hz, 2H), 1.76-1.86 (m, 4H), 1.20-1.51 (m, 36H), 0.86 (t, J=6.3 Hz, 6H). 13C {1H} NMR (75 MHz, CDCl3, δ): 193.77, 192.45, 155.19, 149.28, 138.17, 132.46, 130.90, 126.16, 125.47, 111.94, 111.46, 103.28, 69.21, 69.15, 32.00, 29.75, 29.70, 29.66, 29.45, 29.40, 29.10, 28.94, 26.06, 25.98, 22.78, 14.24. HRMS-EI (m/z): [M]+ calcd for C38H57IO4, 704.33016; found, 704.32941. Anal. calcd for C38H57IO4: C, 64.76; H, 8.15. Found: C, 64.81; H, 8.15.
Reaction SMILES: [O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:11]([OH:13])=O)[CH:8]=2)[NH:3]1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[CH3:56][O:57][CH2:58][CH2:59][NH2:60].C(=O)([O-])O.[Na+]>C(#N)C.CN(C)C=O>[CH3:56][O:57][CH2:58][CH2:59][NH:60][C:11]([C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[NH:3][C:2](=[O:1])[CH2:10]2)=[O:13]
Reactant: O=C1Cc2cc(C(=O)O)ccc2N1
Reactant: COCCN
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: O=C([O-])O
Solvent: CC#N
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COCCNC(=O)c1ccc2c(c1)CC(=O)N2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 57 %

Procedure:
2-Oxoindoline-5-carboxylic acid (0.470 g, 2.66 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (1.010 g, 3.15 mmol), 1-hydroxybenzotriazole hydrate (0.417 g, 3.09 mmol) and N,N-diisopropylethylamine (0.7 mL, 4.0 mmol) were suspended in acetonitrile/N,N-dimethylformamide, (10 mL:2 mL), and stirred at room temperature for 30 min. 2-Methoxyethanamine (0.516 g, 6.88 mmol) was added and stirring was continued for 2 h. Saturated aqueous sodium hydrogencarbonate was added (10 mL) and the solvents were removed in vacuo. The residue was purified on a silica gel column using a gradient chloroform/methanol, (100:1 to 1:1), as the eluent to give 0.355 g (57% yield) of the title compound as a solid: 1H NMR (DMSO-d6, 400 MHz) δ 10.59 (s, 1H), 8.31 (m, 1H), 7.72 (d, J=7 Hz, 1H), 7.71 (s, 1H), 6.83 (d, J=8 Hz, 1H), 3.51 (s, 2H), 3.42 (m, 2H), 3.39 (m, 2H), 3.24 (s, 3H); MS (ES) m/z 235 (M++1).
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.S(=O)(=O)(O)O.[I:23]N1C(=O)CCC1=O>C(O)(=O)C.ClCCl.CC#N>[I:23][C:11]1[CH:10]=[C:9]([C:6]2[CH:7]=[N:8][C:3]([C:2]([F:1])([F:16])[F:17])=[CH:4][CH:5]=2)[CH:14]=[CH:13][C:12]=1[OH:15]
Reactant: O=C1CCC(=O)N1I
Reactant: Oc1ccc(-c2ccc(C(F)(F)F)nc2)cc1
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Solvent: ClCCl
Solvent: CC#N
Product: Oc1ccc(-c2ccc(C(F)(F)F)nc2)cc1I
Temperature: 25 °C
Reaction time: 18 h

Procedure:
4-(6-(Trifluoromethyl)pyridin-3-yl)phenol (Preparation 61, 1.24 g, 5.18 mmol) was dissolved in a mixture of acetic acid (10 mL), dichloromethane (10 mL) and CH3CN (10 mL) at room temperature. Concentrated sulphuric acid (0.5 mL) was then added followed by N-iodosuccinimide (1.052 g, 4.67 mmol). The reaction was stirred at room temperature for 18 hours. A further aliquot of N-iodosuccinimide (116 mg, 0.518 mmol) was added and the reaction mixture was stirred for one hour and concentrated in vacuo. The crude oil was purified on silica gel by Biotage™ (5% to 60% of EtOAc in heptane over 20 CV) and fractions containing product were evaporated to give an inseparable mixture of product/starting material 7:3 (840 mg). This was used directly in the next stage without further purification.
Reaction SMILES: NC1N=C(OCCCC)N=C2C=1N=C(OC)N2CCCC1CCCCN1C(OCC1C=CC=CC=1)=O.FC(F)(F)C(O)=O.[CH3:44][C@H:45]([O:49][C:50]1[N:58]=[C:57]2[C:53]([N:54]=[C:55]([O:59][CH3:60])[NH:56]2)=[C:52]([NH2:61])[N:51]=1)[CH2:46][CH2:47][CH3:48].Br[CH2:63][CH2:64][CH:65]1[CH2:70][CH2:69][N:68]([C:71]([O:73][CH2:74][C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=2)=[O:72])[CH2:67][CH2:66]1>>[NH2:61][C:52]1[N:51]=[C:50]([O:49][C@@H:45]([CH3:44])[CH2:46][CH2:47][CH3:48])[N:58]=[C:57]2[C:53]=1[N:54]=[C:55]([O:59][CH3:60])[N:56]2[CH2:63][CH2:64][CH:65]1[CH2:66][CH2:67][N:68]([C:71]([O:73][CH2:74][C:75]2[CH:76]=[CH:77][CH:78]=[CH:79][CH:80]=2)=[O:72])[CH2:69][CH2:70]1
Reactant: O=C(OCc1ccccc1)N1CCC(CCBr)CC1
Reactant: CCC[C@H](C)Oc1nc(N)c2nc(OC)[nH]c2n1
Agent: CCCCOc1nc(N)c2nc(OC)n(CCCC3CCCCN3C(=O)OCc3ccccc3)c2n1
Solvent: O=C(O)C(F)(F)F
Product: CCC[C@H](C)Oc1nc(N)c2nc(OC)n(CCC3CCN(C(=O)OCc4ccccc4)CC3)c2n1

Procedure:
Prepared similarly to Intermediate 31 from 2-{[(1S)-1-methylbutyl]oxy}-8-(methyloxy)-9H-purin-6-amine trifluoroacetate salt and phenylmethyl 4-(2-bromoethyl)-1-piperidinecarboxylate.
Reaction SMILES: [C:1]1([C:7](=O)[CH:8]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][CH:13]=2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(C)C(C)=CC=CC=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:38].S>C(O)C>[C:1]1([C:7]2[S:38][C:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][CH:13]=3)=[CH:9][C:8]=2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Reactant: CC(C)(C)c1ccc(C(=O)CC(C(=O)c2ccccc2)c2ccccc2)cc1
Agent: S
Solvent: CCO
Solvent: Cc1ccccc1C
Product: CC(C)(C)c1ccc(-c2cc(-c3ccccc3)c(-c3ccccc3)s2)cc1

Procedure:
A 1-liter stirred autoclave was charged with 55.6 g (0.150 mole) of 1,2-diphenyl-4-p-t-butylphenylbutane-1,4-dione, 100 ml of xylene, 33.3 g (0.075 mole) of phosphorus pentasulfide and 130 g of hydrogen sulfide. The reactor was cooled and vented. The residue was stirred with 150 ml of absolute ethanol. Filtration gave a first crop of 18 g (32.6%) m.p. 108°-112° C. Chilling the filtrate and refiltering gave a second crop of 24 g (43.4%) m.p. 102°-105° C. The two crops were combined for recrystallization from a mixture of 50 ml of dioxane and 100 ml of absolute ehtanol. The pure product (31.3 g, 56.6%) had a m.p. of 117°-119° C.
Reaction SMILES: [OH:1][NH2:2].C([O:5][C:6](=O)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12]=[C:13]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1)C>CO>[OH:1][NH:2][C:6](=[O:5])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12]=[C:13]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1
Reactant: NO
Reactant: CCOC(=O)CCCCCC=C(c1ccccn1)c1ccccn1
Solvent: CO
Product: O=C(CCCCCC=C(c1ccccn1)c1ccccn1)NO
Reaction time: 72 h
Yield: 18 %

Procedure:
HONH2 (50% aqueous, 0.5 mL) was added to II (68 mg, 0.21 mmol) in MeOH (0.5 mL) at rt. The reaction mixture was stirred for 72 h, after which the solvents were evaporated under reduced pressure. The resulting residue was dissolved and co-evaporated with toluene (2×5 mL), then was purified by silica gel column chromatography eluting with CH2Cl2/MeOH (100:1 to 100:10) to furnish III as a colourless oil (12 mg, 18%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:26])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[NH:16][C:17]([N:19]2[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]2)=O)=[N:6][CH:7]=1.[NH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:26])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[NH:16][CH2:17][N:19]2[CH2:24][CH2:23][CH:22]([N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)[CH2:21][CH2:20]2)=[N:6][CH:7]=1
Reactant: O=C1CCN(C(=O)Nc2ccccc2C(=O)Nc2ccc(Cl)cn2)CC1
Reactant: C1CCNC1
Product: O=C(Nc1ccc(Cl)cn1)c1ccccc1NCN1CCC(N2CCCC2)CC1

Procedure:
Using a similar procedure to that described in Example 9-C, N-(5-chloropyridin-2-yl)-2-(4-oxopiperidin-1-ylcarbonyl)aminobenzamide (100 mg, 0.268 mmol) and pyrolidine (0.045 mL, 0.54 mmol) yielded the title compound.
Reaction SMILES: [CH3:1][C:2]1[C:7]([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C1C(=O)[N:46](Br)[C:44](=O)C1.[C-]#N.[Na+]>C(Cl)Cl.CN(C=O)C.C(OCC)(=O)C>[CH:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:16]=[CH:17][C:8]=1[C:7]1[C:2]([CH2:1][C:44]#[N:46])=[C:3]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:4]=[CH:5][CH:6]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1c(-c2ccccc2)cccc1-c1ccc2ccccc2c1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Agent: [C-]#N
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: N#CCc1c(-c2ccccc2)cccc1-c1ccc2ccccc2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 52.9 %

Procedure:
A solution of 2-(2-methyl-1,1′-biphenyl-3-yl)naphthalene (2.0 g, 6.8 mmol) and 200 mg of benzoyl peroxide was refluxed, then NBS (1.21 g, 6.8 mmol) was added. The reaction mixture was refluxed overnight, diluted with methylene chloride, washed with water and dried over MgSO4. Removal of solvent under reduced pressure gave a crude product. The crude product was dissolved in 20 mL of DMF and sodium cyanide (0.65 g, 13 mmol) was added. The reaction was stirred at room temperature for 2 hours, diluted with ethyl acetate, washed with water and dried over MgSO4. Removal of solvent under reduced pressure gave a crude product that was purified by silica gel chromatography eluting with 0.4% ethyl acetate/hexanes to give 1.15 g of (3-naphthalen-2-yl-biphenyl-2-yl)-acetonitrile: 1H NMR (CDCl3): δ 3.43 (s, 2H), 7.30-7.60 (m, 11H), 7.80-7.95 (m, 4H).
Reaction SMILES: [N+:1]([CH2:4][CH2:5][CH3:6])([O-:3])=[O:2].C(O[CH:10]([OH:15])[C:11]([F:14])([F:13])[F:12])C.C([O-])([O-])=O.[K+].[K+].Cl>[Cl-].[Na+].O>[F:14][C:11]([F:12])([F:13])[CH:10]([OH:15])[CH:4]([N+:1]([O-:3])=[O:2])[CH2:5][CH3:6]
Reactant: CCOC(O)C(F)(F)F
Reactant: CCC[N+](=O)[O-]
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: O
Product: CCC(C(O)C(F)(F)F)[N+](=O)[O-]
Temperature: 60 °C
Reaction time: 3 h
Yield: 64.2 %

Procedure:
1-Nitropropane (3.25 g, 36.6 mmol), trifluoroacetaldehyde ethyl hemiacetal (5.85 g, 36.6 mmol, 90% purity) and powdered K2CO3 (0.34 g, 2.5 mmol) were mixed and stirred at 60° C. for 3 h and then at room temperature for 3 days. Brine (10 ml) and 1N aqueous HCl (10 ml) were added and the lower organic layer separated. The aqueous layer was extracted with ether (2×30 ml) and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under vacuum. The residue was purified by flash chromatography on silica gel with a gradient elution of CH2Cl2:hexane (50:50), CH2Cl2:hexane (75:25), CH2Cl2 (100%) and MeOH:CH2Cl2 (5:95) to give the product as a waxy white solid (4.4 g, 64%). δH (CDCl3, 500 MHz) 1.04-1.00 (3 H, m, CHCH2CH3), 2.16-1.99 (2 H, m, CHCH2CH3), 4.37 (1 H, s, b, OH), 4.71-4.59 (2 H, m, 2×CH); δC (CDCl3, 500 MHz) dq (126.79, 126.70; 124.55, 124.46; 122.30, 122.21; 120.06, 119.96, CF3), two peaks (88.34, 87.60 CH NO2), eight peaks (71.13, 70.87, 70.81, 70.62, 70.56, 70.36, 70.30, 70.05 CHOH), two peaks (23.57 and 21.98 CH2), two peaks (9.77 and 9.66 CH3); 71.5 (CH), 54.03 (CH), 25.5 (CH2), 11.05 (CH3). 19F NMR δ −76.2 and −77.5
Reaction SMILES: [I-].[CH3:2][S+](C)C.[H-].[Na+].[C:8]1([CH:20]2[CH2:25][CH2:24][C:23](=[CH:26][C:27]#[N:28])[CH2:22][CH2:21]2)[N:9]=[N:10][N:11]2[C:16]=1[C:15]1[CH:17]=[CH:18][NH:19][C:14]=1[N:13]=[CH:12]2.O>CS(C)=O>[C:8]1([CH:20]2[CH2:21][CH2:22][C:23]3([CH:26]([C:27]#[N:28])[CH2:2]3)[CH2:24][CH2:25]2)[N:9]=[N:10][N:11]2[C:16]=1[C:15]1[CH:17]=[CH:18][NH:19][C:14]=1[N:13]=[CH:12]2
Reactant: N#CC=C1CCC(c2nnn3cnc4[nH]ccc4c23)CC1
Reactant: C[S+](C)C
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: N#CC1CC12CCC(c1nnn3cnc4[nH]ccc4c13)CC2
Temperature: 25 °C
Reaction time: 15 h
Yield: 36.8 %

Procedure:
Trimethylsulfonium iodide (59.0 μL, 0.269 mmol) in dimethyl sulfoxide (1 mL) was stirred with sodium hydride (55 wt % dispersion in mineral oil, 12.0 mg, 0.269 mmol) at room temperature for 30 minutes. The reaction mixture was mixed with 2-[4-(7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidin-1-yl)cyclohexylidene]acetonitrile (15.0 mg, 0.0539 mmol) obtained in Synthetic Examplea 434 and then stirred at room temperature for 15 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/1 (v/v)) to give the title compound as a colorless solid (5.80 mg, yield 37%).
Reaction SMILES: [C:1]1([CH:7]([OH:16])[CH2:8][C:9](=[O:15])[CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([BH3-])#N.[Na+].O.Cl>CO.CC(C)[O-].CC(C)[O-].CC(C)[O-].[Cl-].[Ti+4]>[C:1]1([CH:7]([OH:16])[CH2:8][CH:9]([OH:15])[CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COC(=O)CC(=O)CC(O)c1ccccc1
Agent: [Ti+4]
Agent: CC(C)[O-]
Agent: Cl
Solvent: O
Solvent: CO
Product: COC(=O)CC(O)CC(O)c1ccccc1
Temperature: -10 °C
Reaction time: 0.33 h
Yield: 69.3 %

Procedure:
1.03 g of methyl 5-phenyl-5-hydroxy-3-oxo-pentanoate is dissolved in 40 cm3 methanol. The solution is cooled to -10° C. and then 1.3 cm3 of 95% titanium chloride triisopropoxide (4.5 mmol) are added. The mixture is stirred for 20 minutes at -10° C. and then 329.6 mg of 95% sodium cyanoborohydride (50 mmol) are added. The mixture is stirred for 3 hours at a temperature between -5° and 0° C. 10 cm3 of water and 1 cm3 of concentrated hydrochloric acid are then added. After evaporation of the methanol under reduced pressure, the mixture is taken up in 70 cm3 of dichloromethane. The organic phase is washed with 2 times 50 cm3 of water and then dried over sodium sulphate. After filtration and concentration under reduced pressure, the product obtained is treated twice with methanol. There is thus obtained, with a yield of 70%, 720 mg of methyl 5-phenyl-3,5-dihydroxypentanoate for which the syn/anti ratio is equal to 93/7.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]Cl)=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.[Cl:17][C:18]1[CH:32]=[C:31]([O:33][C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[CH:35]=2)[CH:30]=[CH:29][C:19]=1[O:20][CH2:21][CH2:22][O:23][C:24]([NH:26][CH2:27][CH3:28])=[O:25].N1C=CC=CC=1>CCOCC>[Cl:17][C:18]1[CH:32]=[C:31]([O:33][C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[CH:35]=2)[CH:30]=[CH:29][C:19]=1[O:20][CH2:21][CH2:22][O:23][C:24]([N:26]([CH2:27][CH3:28])[S:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)=[O:25]
Reactant: ClSc1ccc(Cl)cc1
Reactant: CCNC(=O)OCCOc1ccc(Oc2cccc(Cl)c2)cc1Cl
Solvent: CCOCC
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CCN(Sc1ccc(Cl)cc1)C(=O)OCCOc1ccc(Oc2cccc(Cl)c2)cc1Cl
Reaction time: 16 h

Procedure:
A solution of 2 g of 4-chlorophenylsulfenyl chloride in 1 0 ml of toluene is added dropwise with stirring at 0°-5° C. in the course of approximately 30 minutes to a mixture of 3.7 g of 1-[2-chloro-4-(3-chlorophenoxy)phenoxy]2-ethylaminocarbonyloxyethane, 10 ml of pyridine and 10 ml of toluene, and stirring is continued for 16 hours at room temperature. The reaction mixture is diluted with 100 ml of ether, washed three times using ice-cold 1N hydrochloric acid and three times using water, the organic phase is dried over sodium sulfate and the solvent is evaporated in vacuo. The crude product is purified on silica gel using diethyl ether/n-hexane (1:3) as mobile phase. This gives the title compound of refractive index nD20 1.6209.
Reaction SMILES: [CH2:1]([S:3]([C:6]1[N:10]=[CH:9][NH:8][N:7]=1)(=[O:5])=[O:4])[CH3:2].[CH2:11]([N:14]([CH2:18][CH2:19][CH3:20])[C:15](Cl)=[O:16])[CH2:12][CH3:13]>>[CH2:11]([N:14]([CH2:18][CH2:19][CH3:20])[C:15]([N:8]1[CH:9]=[N:10][C:6]([S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])=[N:7]1)=[O:16])[CH2:12][CH3:13]
Reactant: CCCN(CCC)C(=O)Cl
Reactant: CCS(=O)(=O)c1nc[nH]n1
Product: CCCN(CCC)C(=O)n1cnc(S(=O)(=O)CC)n1

Procedure:
In an analogous manner to that described in Example 20, 3-ethylsulphonyl-1,2,4-triazole was reacted with dipropylcarbamoyl chloride to give 1-dipropylcarbamoyl-3-ethylsulphonyl-1,2,4-triazole, m.p. 44° - 45° C. Elemental analysis satisfactory.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([NH:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:3]=1.O.[NH2:27][NH2:28]>CCO>[NH2:13][C:12]1[C:11]2[C:10](=[CH:9][C:8]([C:6]3[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([NH:17][CH2:18][CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH:5]=3)=[CH:15][CH:14]=2)[NH:28][N:27]=1
Reactant: NN
Reactant: N#Cc1ccc(-c2cc(NCCc3ccccc3)nc(N)n2)cc1F
Solvent: CCO
Solvent: O
Product: Nc1nc(NCCc2ccccc2)cc(-c2ccc3c(N)n[nH]c3c2)n1
Temperature: 95 °C
Reaction time: 8 h
Yield: 42 %

Procedure:
To a solution of 4-{2-amino-6-[(2-phenylethyl)amino]-4-pyrimidinyl}-2-fluorobenzonitrile (800 mg, 2.4 mmol) in EtOH (20 mL) was added hydrazine monohydrate (7 mL), and the resulting suspension was stirred overnight at 95° C. The clear reaction mixture was concentrated, and the resulting residue was purified by RPHPLC (CH3CN/H2O w/0.1% THF) to afford the title compound (500 mg, 42%) as a light yellow powder. LC-MS (ES) m/z=346 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 2.85 (t, J=7.2 Hz, 2H), 3.53 (m, 2H), 5.37 (s, 2H), 6.02 (s, 2H), 6.28 (s, 1H), 6.94 (s, 1H), 7.18-7.23 (m, 1H), 7.28-7.33 (m, 4H), 7.42 (d, J=8.4 Hz, 1H), 7.70 (d, J=8.4 Hz, 1H), 7.85 (s, 1H), 11.5 (s, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Cl-].[Ru+2].[Fe]>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:10])[CH3:9])=[CH:4][CH:3]=1
Reactant: CC(=O)c1ccc(N)cc1
Agent: [Fe]
Agent: [Ru+2]
Agent: O=C([O-])[O-]
Solvent: C1CCOC1
Product: CC(O)c1ccc(N)cc1
Temperature: 65 °C
Reaction time: 1 h

Procedure:
Tris(triphenylphosphine)ruthenium(II) chloride (1.9 mg, 2 μmol, 0.5 mol %) and a chiral ligand (M=Fe, R=t-Bu, Ar=3,5-(CF3)2C6H3—, 1.3 μmol, 0.33 mol %) were dissolved in tetrahydrofuran (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 65° C. After the mixture was cooled to room temperature, p-amino-acetophenone (0.4 mmol), tetrahydrofuran (2 mL) and an aqueous solution of sodium carbonate (0.4 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 48 h under H2 (20 atm) at 0° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/1). Accordingly, pure 1-(p-aminophenyl)ethanol was obtained and the ee value (ee=97%) was measured by GC analysis.
Reaction SMILES: Cl.[CH2:2]([O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][CH2:9][C@@H:8]1[NH2:13])=[O:6])[CH3:3].[C:14]1(=O)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO.C(O)(=O)C>[CH2:2]([O:4][C:5]([CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH:8]1[NH:13][CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)=[O:6])[CH3:3]
Reactant: O=C1CCCCC1
Reactant: CCOC(=O)[C@@H]1CCCC[C@@H]1N
Agent: Cl
Agent: O=C([O-])O
Agent: [BH3-]C#N
Solvent: CC(=O)O
Solvent: CO
Product: CCOC(=O)C1CCCCC1NC1CCCCC1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 62.3 %

Procedure:
cis-2-Amino-cyclohexanecarboxylic acid ethyl ester hydrochloride (0.5 g, 2.407 mmol) was dissolved in methanol (25 mL). Cyclohexanone (0.236 g, 2.407 mmol) was added followed by acetic acid (0.1 mL). The solution was stirred at 25° C. for 10 min. Sodium cyanoborohydride (0.378 g, 6.018 mmol) was added and the mixture was stirred at 25° C. for 16 h. The mixture was poured into 1/2 saturated aqueous sodium bicarbonate solution (300 mL). The aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to afford the crude product, 2-cyclohexylamino-cyclohexanecarboxylic acid ethyl ester (0.38 g, 1.5 mmol, 62.4%), as a clear oil. LC-MS (ESI) calcd for C15H27NO2 253.20, found 253.9 [M+H+].