Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][C:6]([O:9][CH2:10][CH3:11])([OH:8])[CH3:7])[CH3:4].[CH2:12](Cl)[C:13](=[CH2:15])[CH3:14]>C1COCC1>[CH2:12]([O:8][C:6]([O:9][CH2:10][CH3:11])([O:5][CH2:3][CH3:4])[CH3:7])[C:13](=[CH2:15])[CH3:14]
Reactant: C=C(C)CCl
Reactant: CCOC(C)(O)OCC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: C=C(C)COC(C)(OCC)OCC
Yield: 90 %

Procedure:
To a cold (0° C.) suspension of NaH (2.68 g, 60%) in THF (150 mL) was added a solution of 1,1-diethoxyethanol [which was prepared according to the literature procedure of Zirkle, C. L. et. al. J. Org. Chem. 1961, 26, 395-407] (9.00 g) in THF (20 mL), and the reaction mixture was stirred at room temperature for 1 hour before adding methallyl chloride (8.0 mL). The reaction mixture was heated to reflux overnight, cooled and filtered through a plug of celite. Solvent was removed by rotary evaporation, and the residue purified by column chromatography (silica, 20% ether/hexane) to give 1,1-diethoxyethyl methallyl ether (11.5, 90%). Ozonolysis of a chilled (-30° C.) solution of this ether (6.00 g) in EtOAc (80 mL) was carried out until no starting material was detectable by TLC (1 hour). At this time, the reaction was purged with oxygen, treated with Pd(OH)2 (150 mg) and stirred under an atmosphere of hydrogen overnight. The catalyst was filtered away, and the filtrate was concentrated by rotary evaporation. The resulting residue was purified by column chromatography (silica, 20% EtOAc/hexane) to afford the title compound (4.53 g, 82%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][OH:5].C(N(CC)CC)C.[CH3:13][S:14](Cl)(=[O:16])=[O:15]>ClCCl>[CH3:13][S:14]([NH:1][CH2:2][CH2:3][CH2:4][O:5][S:14]([CH3:13])(=[O:16])=[O:15])(=[O:16])=[O:15]
Reactant: NCCCO
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)NCCCOS(C)(=O)=O
Yield: 69.8 %

Procedure:
To a solution of 3-amino-1-propanol (11.47 ml, 150 mmoles) and triethylamine (46 ml, 330 mmoles) in dichloromethane (250 ml) was added methylsulfonyl chloride (25.5 ml, 330 mmoles) with stirring under ice-cooling and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was washed in turn with an aqueous sodium bicarbnonate and water and dried. After the solvent was distilled off, the residue was purified by column chromatography (eluent: ethyl acetate) to obtain 24.22 g of the desired product (69.8%, white crystals).
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].CCN(CC)CC.[C:19](Cl)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1>[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10]
Reactant: O=C(Cl)c1ccccc1
Reactant: Nc1ccc(F)c([N+](=O)[O-])c1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C(Nc1ccc(F)c([N+](=O)[O-])c1)c1ccccc1
Temperature: 5 °C
Reaction time: 1 h
Yield: 81.1 %

Procedure:
To a solution of 4-fluoro-3-nitroaniline (2.00 g, 12.8 mmol) and Et3N (1.98 mL, 14.1 mmol) in THF (40 mL) was added benzoyl chloride (1.58 ml, 13.5 mmol) dropwise at 5° C. The mixture was stirred at 5° C. for 1 hour, warmed to room temperature, and then evaporated. The residue was suspended in H2O (100 ml), adjusted to pH 2, and then extracted with EtOAc. The extract was washed with H2O, 10% NaHCO3 and brine, dried over MgSO4, and concentrated under vacuum to give the crude product, which was purified by washing with i-Pr2O to give the title compound as pale brown crystal (2.70 g, 81%).
Reaction SMILES: [C:1]1([C:7]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:8]=[N:9][C:10]2[N:15]=[N:14][C:13]([O:16][CH2:17][CH:18]([OH:21])[CH2:19][OH:20])=[CH:12][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C(O)C.O1CCCC1.[Pd]>[OH:21][CH:18]([CH2:19][OH:20])[CH2:17][O:16][C:13]1[N:14]=[N:15][C:10]([NH:9][NH:8][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:11][CH:12]=1
Reactant: OCC(O)COc1ccc(N=NC(c2ccccc2)(c2ccccc2)c2ccccc2)nn1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: OCC(O)COc1ccc(NNC(c2ccccc2)(c2ccccc2)c2ccccc2)nn1
Yield: 58.4 %

Procedure:
Into a solution of (RS)-3-[(6-triphenylmethylazo-3-pyridazinyl)oxy]-1.2-propanediol (5.45 g) in 95% ethanol (100 ml) and tetrahydrofuran (50 ml) containing 5% palladium on charcoal (1.1 g) hydrogen was bubbled, at room temperature, for 16 hours. Removal of the catalyst and evaporation of the solvent gave a residue which was crystallized from 2-propanol to yield 3.2 g of the title compound. m.p. 174°-176° C. Mass spectrum (E.I. 70 eV, 1.5 mA), m/z=412 (M-N2H2)+, 338 (M-C3H8N2O2)+, 243 (Ph3C)+.
Reaction SMILES: [CH3:1][CH:2]([CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[OH:3].N1C=CC=CC=1.[C:19]1([CH3:29])[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[CH:21][CH:20]=1>O>[C:7]1([CH2:6][O:5][CH2:4][CH:2]([O:3][S:25]([C:22]2[CH:23]=[CH:24][C:19]([CH3:29])=[CH:20][CH:21]=2)(=[O:27])=[O:26])[CH3:1])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: CC(O)COCc1ccccc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Solvent: O
Product: Cc1ccc(S(=O)(=O)OC(C)COCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 96 h
Yield: 73.9 %

Procedure:
CH3CH(OH)CH2OCH2Ph (50.0 g) and pyridine (150 ml) were put into a flask, and under cooling with ice, p-toluenesulfonic acid chloride (63.2 g) was added over a period of 30 minutes. The mixture was stirred at room temperature for 4 days, and then water (150 ml) was added, followed by extraction twice with dichloromethane (100 ml). The extracted organic phase was washed twice with a KHCO3 saturated aqueous solution (100 ml) and twice with water (100 ml), dried over magnesium sulfate, filtered and further concentrated to obtain PhCH2OCH2CH(CH3)OTs (71.2 g).
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[CH:10]([CH:21]([OH:31])[CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl:51][C:52]1[CH:53]=[CH:54][C:55](O)=[N:56][CH:57]=1.C1C=CC(COC(/N=N/C(OCC2C=CC=CC=2)=O)=O)=CC=1>C1COCC1.C(OCC)(=O)C>[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=2)[CH:10]([CH:21]([O:31][C:55]2[CH:54]=[CH:53][C:52]([Cl:51])=[CH:57][N:56]=2)[CH2:22][O:23][Si:24]([C:27]([CH3:28])([CH3:30])[CH3:29])([CH3:26])[CH3:25])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Oc1ccc(Cl)cn1
Reactant: CC(C)(C)[Si](C)(C)OCC(O)C1CN(Cc2ccccc2)CC1c1ccc(Cl)c(Cl)c1
Agent: O=C(/N=N/C(=O)OCc1ccccc1)OCc1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OCC(Oc1ccc(Cl)cn1)C1CN(Cc2ccccc2)CC1c1ccc(Cl)c(Cl)c1
Temperature: 40 °C
Yield: 44 %

Procedure:
(SR)-1-[(3SR,4RS)-1-Benzyl-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-2-(tert-butyl-dimethyl-silanyloxy)-ethanol (described herein above) (13.2 mg. 0.0275 mmol) and PPh3 (PPh3 polymer bound, 3 mmol PPh3/g resin) (18 mg, 0.055 mmol) were suspended in THF (2 mL). To the mixture were added 5-chloro-pyridin-2-ol (7 mg, 0.055 mmol) and then DBAD (13 mg, 0.055 mmol). The reaction mixture was stirred at 40° C. over night. The mixture was diluted with ethyl acetate and filtered on celite and concentrated under vacuo. The residue was purified by TLC (SiO2, EtOAc/H, 1:4) yielded 7.2 mg (44%) of the title compound as a colorless oil. ES-MS m/e: 593.3 (M+H+).
Reaction SMILES: [CH3:1][CH:2]([C:4]1[N:8]([CH2:9][CH2:10][C@@H:11]([OH:19])[CH2:12][C@@H:13]([OH:18])[CH2:14][C:15]([OH:17])=O)[C:7]([C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)=[C:6]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:5]=1[C:33](NC1C=CC=CC=1)=[O:34])[CH3:3].[OH-:42].[Na+].Cl>C1COCC1.O>[F:26][C:23]1[CH:24]=[CH:25][C:20]([C:7]2[N:8]([CH2:9][CH2:10][C@@H:11]3[CH2:12][C@@H:13]([OH:18])[CH2:14][C:15](=[O:17])[O:19]3)[C:4]([CH:2]([CH3:3])[CH3:1])=[C:5]([C:33]([OH:34])=[O:42])[C:6]=2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:21][CH:22]=1
Reactant: [OH-]
Reactant: CC(C)c1c(C(=O)Nc2ccccc2)c(-c2ccccc2)c(-c2ccc(F)cc2)n1CC[C@@H](O)C[C@@H](O)CC(=O)O
Agent: Cl
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)c1c(C(=O)O)c(-c2ccccc2)c(-c2ccc(F)cc2)n1CC[C@@H]1C[C@@H](O)CC(=O)O1

Procedure:
A solution of atorvastatin (prepared as described in U.S. Pat. Nos. 5,397,792 and 5,446,054) (1 mmol) and NaOH (10 mmol) in THF (30 mL) and water (10 mL) is maintained at 50° C. The progress of the reaction is monitored by tlc. When the reaction is complete, the solution is acidified with dilute HCl and extracted with CH2Cl2. The extract is then dried and evaporated. The residue is dissolved in toluene (50 mL) and the solution is heated at reflux until tlc monitoring shows that formation of the lactone moiety is complete. The solvent is removed under reduced pressure and compound 18 is purified by chromatography.
Reaction SMILES: [NH:1]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:2][C:3]([NH:5][CH2:6][C:7]([NH:9][C@H:10]([C:18]([NH:20][C@H:21]([C:26](O)=[O:27])[CH2:22][CH2:23][S:24][CH3:25])=[O:19])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:8])=[O:4].[NH2:36][C@H:37]([C:41]([NH:43][C@H:44]([C:47]([NH:49][C@H:50]([C:60]([NH:62][C@H:63]([C:76]([O:78][CH3:79])=[O:77])[CH2:64][CH2:65][CH2:66][CH2:67][NH:68][C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])=[O:61])[CH2:51][CH2:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:48])[CH2:45][OH:46])=[O:42])[C@@H:38]([CH3:40])[OH:39].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>>[NH:1]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:2][C:3]([NH:5][CH2:6][C:7]([NH:9][C@H:10]([C:18]([NH:20][C@H:21]([C:26]([NH:36][C@H:37]([C:41]([NH:43][C@H:44]([C:47]([NH:49][C@H:50]([C:60]([NH:62][C@H:63]([C:76]([O:78][CH3:79])=[O:77])[CH2:64][CH2:65][CH2:66][CH2:67][NH:68][C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])=[O:61])[CH2:51][CH2:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:56])[CH3:57])=[O:48])[CH2:45][OH:46])=[O:42])[C@@H:38]([CH3:40])[OH:39])=[O:27])[CH2:22][CH2:23][S:24][CH3:25])=[O:19])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:8])=[O:4]
Reactant: CSCC[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)OC(C)(C)C)C(=O)O
Reactant: COC(=O)[C@H](CCCCNC(=O)OC(C)(C)C)NC(=O)[C@H](CCC(=O)OC(C)(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](N)[C@@H](C)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Product: COC(=O)[C@H](CCCCNC(=O)OC(C)(C)C)NC(=O)[C@H](CCC(=O)OC(C)(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)OC(C)(C)C)[C@@H](C)O

Procedure:
2.4 g Boc-Gly-Gly-Phe-Met-OH, A(4), and 3.15 g H-Thr-Ser-Glu(OtBu)-Lys(Boc)-OMe, B(3), are coupled with the aid of 2 eq HOBt and 1 eq DCCI in the way described in B(1).
Reaction SMILES: [OH:1][CH:2]1[CH2:5][N:4]([C:6]([C:8]2[O:9][C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[N:11][N:12]=2)=[O:7])[CH2:3]1.[CH3:19][C:20]1[CH:25]=[CH:24][C:23]([S:26](Cl)(=[O:28])=[O:27])=[CH:22][CH:21]=1>>[CH3:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([O:1][CH:2]2[CH2:5][N:4]([C:6]([C:8]3[O:9][C:10]([C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=4)=[N:11][N:12]=3)=[O:7])[CH2:3]2)(=[O:28])=[O:27])=[CH:22][CH:21]=1
Reactant: O=C(c1nnc(-c2ccccc2)o1)N1CC(O)C1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Product: Cc1ccc(S(=O)(=O)OC2CN(C(=O)c3nnc(-c4ccccc4)o3)C2)cc1
Yield: 89.6 %

Procedure:
Using a similar protocol as described in Example 2C but employing 1B (250 mg, 1.02 mmol) and 4-methylbenzene-1-sulfonyl chloride (250 mg, 1.31 mmol) as starting materials afforded 365 mg (90%) of 8B as a solid. 1H NMR (500 MHz, CDCl3): δ 2.49 (s, 3H), 4.24 (dd, 1H), 4.47 (dd, 1H), 4.72 (dd, 1H), 4.98 (dd, 1H), 5.22 (m, 1H), 7.41 (d, 2H), 7.53 (t, 2H), 7.59 (t, 1H), 7.82 (d, 2H), 8.14 (d, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[C:26](I)=[N:25][C:24]4[C:19]3=[N:20][CH:21]=[N:22][C:23]=4[NH:28][CH3:29])=[CH:14][CH:13]=2)=[O:10])=[CH:4][C:3]=1[C:30]([F:33])([F:32])[F:31].[CH2:34]([OH:36])[CH3:35]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[C:26]([O:36][CH2:34][CH3:35])=[N:25][C:24]4[C:19]3=[N:20][CH:21]=[N:22][C:23]=4[NH:28][CH3:29])=[CH:14][CH:13]=2)=[O:10])=[CH:4][C:3]=1[C:30]([F:33])([F:32])[F:31]
Reactant: CCO
Reactant: CNc1ncnc2c1nc(I)n2-c1ccc(NC(=O)Nc2ccc(Cl)c(C(F)(F)F)c2)cc1
Product: CCOc1nc2c(NC)ncnc2n1-c1ccc(NC(=O)Nc2ccc(Cl)c(C(F)(F)F)c2)cc1

Procedure:
The title compound can be prepared from 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-[4-(8-iodo-6-(methylamino)purin-9-yl)phenyl]urea and ethanol by using the same techniques as in Example 136.
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:8]=[C:7]([CH:9]([OH:24])[CH2:10][NH:11][CH:12]([CH2:14][CH2:15][N:16]([CH3:23])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:13])[CH:6]=[CH:5][C:4]=1[OH:25].C(OO)(=[O:28])C.C(Cl)(Cl)Cl.CO.N>CO>[CH3:23][N:16]([CH2:15][CH2:14][CH:12]([NH:11][CH2:10][CH:9]([C:7]1[CH:6]=[CH:5][C:4]([OH:25])=[C:3]([S:2]([CH3:1])=[O:28])[CH:8]=1)[OH:24])[CH3:13])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CC(=O)OO
Reactant: CSc1cc(C(O)CNC(C)CCN(C)c2ccccc2)ccc1O
Agent: N
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CC(CCN(C)c1ccccc1)NCC(O)c1ccc(O)c(S(C)=O)c1

Procedure:
To 2-methylthio-4-(2-[4-(methylanilino)-2-butylamino]-1-hydroxyethyl)phenol (1.8 g=5 mmol) in 50 ml methanol add a solution of 40% peracetic acid (5.0 mmol) in 10 ml methanol. Stir one-half hour and concentrate to obtain a gum. Chromatograph on 100 g silica gel using chloroform/methanol/ammonia as eluant and combine appropriate fractions and concentrate to obtain 4-(2-[4-(N-methylanilino)-2-butylamino]-1-hydroxyethyl)-2-methylsulfinylphenol. Dissolve this in ether and treat with ethereal hydrogen chloride to obtain the title product.
Reaction SMILES: [CH:1]([C:3]1[CH:12]=[C:7]([C:8]([O:10][CH3:11])=[O:9])[C:6]([OH:13])=[CH:5][CH:4]=1)=[O:2].[CH2:14](Br)[CH:15]=[CH2:16].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH:1]([C:3]1[CH:4]=[CH:5][C:6]([O:13][CH2:16][CH:15]=[CH2:14])=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9])=[O:2]
Reactant: COC(=O)c1cc(C=O)ccc1O
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C=CCOc1ccc(C=O)cc1C(=O)OC
Yield: 106 %

Procedure:
Methyl 5-formylsalicylate (3.3 g, 18 mmol), allyl bromide (1.7 mL, 20 mmol), and potassium carbonate (2.8 g, 20 mmol) were stirred at room temperature in DMF (20 mL) overnight. After concentration, the mixture was diluted with EtOAc and extracted with water (5×), then brine. After drying (MgSO4), solvent was removed to give a yellow solid (4.2 g). 1H-NMR(300 MHz, CDCl3): 9.92 (s, 1H), 8.35 (d, 1H, J=2 Hz), 8.00 (dd, 1H, J=9,2 Hz), 7.09 (d, 1H, J=9 Hz), 6.13-6.01 (m, 1H), 5.58-5.34 (m, 2H), 4.75-4.73 (m, 2H), 3.93 (s, 3H). Anal. Calc'd for C12H12O4 : C, 65.45; H, 5.49; Found: C, 65.10; H, 5.36.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9](=[CH:13][CH:14]=[CH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)C(O)=O)C=CC=1.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][CH2:29][CH2:30][CH2:31][NH2:32])[CH:23]=1>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:9]=[CH:13][C:14]=1/[C:15](/[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[CH:9]/[CH:5]=[CH:4]/[C:3]([NH:32][CH2:31][CH2:30][CH2:29][CH2:28][C:24]1[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=1)=[O:2]
Reactant: COc1cccc(C(=CC=Cc2ccccc2)C(=O)O)c1
Reactant: NCCCCc1cccnc1
Solvent: C1CCOC1
Product: COc1ccccc1/C(=C/C=C/C(=O)NCCCCc1cccnc1)c1ccccc1
Yield: 114.8 %

Procedure:
As in Example 134, a solution of (2E,4E)-5-(3-methoxyphenyl-5-phenyl-2,4-pentadienoic acid 4(2.96 g) and 3-pyridinebutanamine (1.107 g) in tetrahydrofuran (15 mL) was stirred for 1 hour at room temperature. After the usual work up, the crude amide was purified by HPLC (ethyl acetate) and then crystallized from ethyl acetate-hexane to provide 2.5 g of (2E,4E)-5-(methoxyphenyl)-5-phenyl- N-[4-(3-pyridinyl)butyl]-2,4-pentadienamide mp 66°-68° C.
Reaction SMILES: C(OC(=O)[N:7]([C:17]1[CH:22]=[CH:21][C:20]([CH:23](O)[C:24]2[C:32]3[C:27](=[N:28][CH:29]=[CH:30][N:31]=3)[NH:26][CH:25]=2)=[CH:19][N:18]=1)[CH2:8][C:9]1[CH:10]=[N:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=1)(C)(C)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH3:16][O:15][C:12]1[N:11]=[CH:10][C:9]([CH2:8][NH:7][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][C:24]3[C:32]4[C:27](=[N:28][CH:29]=[CH:30][N:31]=4)[NH:26][CH:25]=3)=[CH:19][N:18]=2)=[CH:14][CH:13]=1
Reactant: COc1ccc(CN(C(=O)OC(C)(C)C)c2ccc(C(O)c3c[nH]c4nccnc34)cn2)cn1
Agent: CC[SiH](CC)CC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(CNc2ccc(Cc3c[nH]c4nccnc34)cn2)cn1
Temperature: 80 °C
Yield: 38.1 %

Procedure:
To {5-[hydroxy-(5H-pyrrolo[2,3-b]pyrazin-7-yl)-methyl]-pyridin-2-yl}-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester (7, 0.220 g, 0.48 mmol) in 10.4 mL of acetonitrile, triethylsilane (2.1 mL 0.013 mol) and trifluoroacetic acid (1.0 mL 0.014 mol) were added. The reaction was heated to 80° C. for 4 hours, then poured into aqueous potassium carbonate, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under vacuum and purified by silica gel column chromatography eluting with methanol:dichloromethane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as a white solid (P-0001, 63.4 mg, 38.5%). MS (ES1): [M+H+]+=347.0.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:24])[N:10]([C@H:12]2[C@H:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[CH2:15][NH:14][CH2:13]2)[CH3:11])=[CH:4][CH:3]=1.[O:25]1[CH2:29][CH2:28][CH:27]([C:30](O)=[O:31])[CH2:26]1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:24])[N:10]([C@H:12]2[C@H:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[CH2:15][N:14]([C:30]([CH:27]3[CH2:28][CH2:29][O:25][CH2:26]3)=[O:31])[CH2:13]2)[CH3:11])=[CH:4][CH:3]=1
Reactant: O=C(O)C1CCOC1
Reactant: CN(C(=O)Oc1ccc(F)cc1)[C@@H]1CNC[C@H]1c1ccc(Cl)cc1
Product: CN(C(=O)Oc1ccc(F)cc1)[C@@H]1CN(C(=O)C2CCOC2)C[C@H]1c1ccc(Cl)cc1

Procedure:
In analogy to the procedure described for the synthesis of example 44 (step c), the title compound [(3S,4R)-4-(4-chloro-phenyl)-1-(tetrahydro-furan-3-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester was prepared from [(3S,4R)-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester instead of [(3S,4R)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester using rac-tetrahydro-3-furoic acid instead of 1-methylcyclopropane-1-carboxylic acid and was obtained as a light brown oil. MS m/e: 447.2 [M+H]+.
Reaction SMILES: [Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.[I:12][C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[CH2:15][OH:16]>ClCCl.CCOCC>[I:12][C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[CH:15]=[O:16]
Reactant: OCc1ccccc1I
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: CCOCC
Solvent: ClCCl
Product: O=Cc1ccccc1I
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 95.9 %

Procedure:
A suspension of pyridinium chlorochromate (8.28 g, 38.4 mmol) and dry celite (5.00 g) in dry dichloromethane was stirred at room temperature for 15 min. 2-Iodobenzyl alcohol (3.03 g, 12.9 mmol) in dry dichloromethane (50 ml) was added. The suspension was shielded from light and stirred at room temperature for 2 h after which it was diluted with ether, and filtered through celite. The cloudy brown filtrate was concentrated to a red-brown gummy solid which was dissolved in dichloromethane and passed through a short silica column, eluting with dichloromethane. The solution was concentrated to give 2-iodobenzaldehyde (19) as a pale yellow oil (2.87 g, 95%).
Reaction SMILES: [C:1]1([CH2:7][C:8]([NH2:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:11]1([CH2:17][CH:18]=[O:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C[Si](C(F)(F)F)(C)C>C(Cl)Cl.C1(C)C=CC=CC=1>[C:1]1([CH2:7][CH:8]([NH:10][C:18](=[O:19])[CH2:17][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[NH:10][C:8](=[O:9])[CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NC(=O)Cc1ccccc1
Reactant: O=CCc1ccccc1
Agent: C[Si](C)(C)C(F)(F)F
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: O=C(Cc1ccccc1)NC(Cc1ccccc1)NC(=O)Cc1ccccc1
Yield: 18.8 %

Procedure:
To a well stirred suspension of 2-phenylacetamide (540 mg, 4 mmol) in dry DCM (2 mL) was added the 2-phenylacetaldehyde (240 mg, 2 mmol) and trimethylsilyltrifluoromethane sulonate (22 mg, 0.1 mmol). The mixture was vigorously stirred for 12 h at room temperature, diluted with toluene (4 mL), and filtered. The precipitate was washed several times with toluene which was recrystallized with methanol and hexane to give the final product (140 mg, 19%). 1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J=7.6 Hz, 2H), 7.14-7.28 (m, 15H), 5.55 (t, J=7.6 Hz, 1H), 3.39 (s, 4H), 2.93 (d, J=7.2 Hz, 2H). LC-MS (ESI): m/z 373.0 (M+H)+.
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1)#[N:2].[CH3:12][C:13]1[CH:18]=[CH:17][C:16]([NH2:19])=[C:15]([NH2:20])[CH:14]=1>>[NH2:2][CH2:1][C:3]1[CH:4]=[CH:5][C:6]([C:7]([NH:19][C:16]2[CH:17]=[CH:18][C:13]([CH3:12])=[CH:14][C:15]=2[NH2:20])=[O:9])=[CH:10][CH:11]=1
Reactant: N#Cc1ccc(C(=O)O)cc1
Reactant: Cc1ccc(N)c(N)c1
Product: Cc1ccc(NC(=O)c2ccc(CN)cc2)c(N)c1
Yield: 33.9 %

Procedure:
The title compound (173 mg, 68% yield) was prepared as a grey solid from 4-cyano-benzoic acid (294 mg, 2 mmol) and 4-methyl-o-phenylenediamine (293 mg, 2.4 mmol) by an analogous procedure to that described in example 8. LC-MS (m/z) 256 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][O:6][C:7]1[CH:8]=[C:9]([CH:14]=[CH:15][CH:16]=1)[C:10]([O:12][CH3:13])=O.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:29])=CC=1>C1(C)C(C)=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][O:6][C:7]1[CH:8]=[C:9]([CH:14]=[CH:15][CH:16]=1)[C:10]([O:12][CH3:13])=[S:29]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: COC(=O)c1cccc(OCc2cccc(Cl)c2)c1
Solvent: Cc1ccccc1C
Product: COC(=S)c1cccc(OCc2cccc(Cl)c2)c1
Yield: 145.9 %

Procedure:
In an analogous manner to that described in Example 1(B), 36.5 g(131.9 mmol) of methyl 3-[(3-chlorobenzyl)oxy]benzoate were heated at reflux for 16 hours with 26.7 g (66 mmol) of Lawesson reagent in xylene and thereafter chromatographed on silica gel. Elution with hexane/toluene (2%, 5% and 10%) yielded 28.2 g (73%) of O-methyl 3-[(3-chlorobenzyl)oxy]thiobenzoate as an orange, crystallizing oil.
Reaction SMILES: [C:1]1([S:7]([C:9]2[CH2:13][CH2:12][O:11][N:10]=2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClC1C=CC=C(C(OO)=[O:22])C=1.O>C(Cl)Cl>[C:1]1([S:7]([C:9]2[CH2:13][CH2:12][O:11][N:10]=2)(=[O:22])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=S(C1=NOCC1)c1ccccc1
Solvent: ClCCl
Solvent: O
Product: O=S(=O)(C1=NOCC1)c1ccccc1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
3-(phenylsulfonyl)-4,5-dihydroisoxazole I-250a and I-250b were prepared by the oxidation of racemic 3-(phenylsulfinyl)-4,5-dihydroisoxazole I-249. 3-(Phenylsulfinyl)-4,5-dihydroisoxazole I-249 is dissolved in methylene chloride (0.03 M). m-Chloroperbenzoic acid (77% by weight, 2.95 equiv) are added in two portions and the reaction is allowed to stir at room temperature for 14 h after which it is transferred to a separatory funnel with excess water and methylene chloride. The organic layer is washed with saturated sodium bicarbonate (2×), dried over magnesium sulfate, and concentrated to provide crude solid that is recrystallized from methylene chloride/hexanes to provide the desired racemic 3-(phenylsulfonyl)-4,5-dihydroisoxazole I-250. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=371.7 m/z. Activity: C