Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3](=O)[CH:4]=[CH:5][CH:6]=[CH:7][CH2:8][S:9]([C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1)=[O:10].[NH2:19][OH:20].[OH-].[K+].CO>C1COCC1>[OH:20][NH:19][C:3](=[O:2])[CH:4]=[CH:5][CH:6]=[CH:7][CH2:8][S:9]([C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1)=[O:10]
Reactant: NO
Reactant: COC(=O)C=CC=CCS(=O)c1ccc(Cl)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(C=CC=CCS(=O)c1ccc(Cl)cc1)NO
Temperature: 0 °C
Reaction time: 1 h
Yield: 56.4 %

Procedure:
To a solution of the 6-(4-chlorobenzenesulfinyl)-hexa-2,4-dienoic acid methyl ester (0.80 g, 2.79 mmol) in distilled THF (15 mL) containing an aqueous solution of hydroxylamine (50%/o, 1.7 ml, 25.8 mmol) was added at 0° C. a solution of potassium hydroxide in methanol (1M, 4.5 ml, 4.5 mmol) over a period of 30 minutes. After stirring at 0° C. for 1 hour, distilled water (15 mL) was added and the mixture was made neutral by dropwise addition of concentrated hydrochloric acid (10 M) at 0° C. The aqueous solution was extracted with ethyl acetate (3×50 mL) and the combined extracts were dried over anhydrous MgSO4, and evaporated to dryness. The residue was recrystallised from acetone to give the title compound (0.45 g, 56%) as a pale brown powder, mp 159° C. (decomp).
Reaction SMILES: [Li+].CC([N-]C(C)C)C.[CH:9]1([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][C:16]2=[O:21])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.[Cl:22][C:23]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=1[CH2:30]Cl>C1COCC1.C(OCC)(=O)C>[Cl:22][C:23]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=1[CH2:30][CH:17]1[CH2:18][CH2:19][CH2:20][N:15]([CH:9]2[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]2)[C:16]1=[O:21]
Reactant: O=C1CCCCN1C1CCCCC1
Reactant: ClCc1ccc(Cl)cc1Cl
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=C1C(Cc2ccc(Cl)cc2Cl)CCCN1C1CCCCC1
Reaction time: 0.25 h
Yield: 242 %

Procedure:
Add 1.8 M LDA (0.9 mL, 1.7 mmol) to solution of 1-cyclohexylpiperidin-2-one (300 mg, 1.7 mmol) in THF (5 mL) at −78° C. and stir for 15 minutes. Add 2,4-dichloro-1-(chloromethyl)benzene (640 mg, 3.3 mmol) and warm the reaction to room temperature. Quench the reaction with water and dilute with ethyl acetate. Dry the organic layer with sodium sulfate, filter and concentrate. Purify the residue by biotage chromatography to afford the title compound as a white solid (1.4 g, 81%): MS (APCI-pos mode) m/z (rel intensity): 340.2 (M+H).
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[S:6][CH:7]=[C:8]([CH2:10]O)[N:9]=1)[CH3:3].Cl.[NH2:13][CH2:14][CH2:15][SH:16].Br>C(O)C>[CH3:1][N:2]([CH2:4][C:5]1[S:6][CH:7]=[C:8]([CH2:10][S:16][CH2:15][CH2:14][NH2:13])[N:9]=1)[CH3:3]
Reactant: NCCS
Reactant: CN(C)Cc1nc(CO)cs1
Agent: Br
Agent: Cl
Solvent: CCO
Product: CN(C)Cc1nc(CSCCN)cs1
Temperature: 100 °C
Reaction time: 11 h

Procedure:
A reaction mixture was prepared from 18.8 g. of 2-dimethylaminomethyl-4-thiazolemethanol, 12.8 g. of 2-aminoethanethiol hydrochloride (cysteamine hydrocloride) and 160 ml. of 48% aqueous hydrobromic acid. The reaction mixture was stirred at about 100° C. for about 11 hours. The volatile constituents were removed in vacuo on a rotary evaporator. Water was added and the volatile constituents again removed by evaporation. The resulting residue, comprising 2-(2-dimethylaminomethyl-4-thiazolylmethylthio)ethylamine trihydrobromide formed in the above reaction, was dissolved in ethanol. The ethanol was evaporated and the resulting residue again dissolved in ethanol. Evaporation of the ethanol yielded a hygroscopic residue which was recrystallized from a methanol-ethyl acetate solvent mixture. 2-(2-Dimethylaminomethyl-4-thiazolylmethylthio)ethylamine trihydrobromide thus prepared had the following physical characteristics:
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6](F)[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[CH:12]1([C:15]2[C:16]([NH:35][S:36]([CH3:39])(=[O:38])=[O:37])=[CH:17][C:18]3[O:22][C:21]([C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)=[C:20]([C:30]([NH:32][CH3:33])=[O:31])[C:19]=3[CH:34]=2)[CH2:14][CH2:13]1.C(=O)([O-])[O-].[K+].[K+]>C(COC)OC.O>[CH:12]1([C:15]2[C:16]([N:35]([C:6]3[CH:5]=[CH:4][C:3]([N+:9]([O-:11])=[O:10])=[C:2]([F:1])[CH:7]=3)[S:36]([CH3:39])(=[O:38])=[O:37])=[CH:17][C:18]3[O:22][C:21]([C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)=[C:20]([C:30]([NH:32][CH3:33])=[O:31])[C:19]=3[CH:34]=2)[CH2:14][CH2:13]1
Reactant: O=[N+]([O-])c1ccc(F)cc1F
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(NS(C)(=O)=O)c(C3CC3)cc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: COCCOC
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(c3ccc([N+](=O)[O-])c(F)c3)S(C)(=O)=O)c(C3CC3)cc12
Temperature: 100 °C
Yield: 28.9 %

Procedure:
A suspension of 2,4-difluoro-1-nitrobenzene (261 mg, 1.64 mmol) and 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-[(methylsulfonyl)amino]-1-benzofuran-3-carboxamide (600 mg, 1.49 mmol) in dimethoxyethane (0.8 mL) and water (0.2 mL) was treated with potassium carbonate (616.86 mg, 4.47 mmol) and heated to 100° C. for 24 hours. The reaction mixture was concentrated and purified by column chromatography to afford 5-cyclopropyl-6-(N-(3-fluoro-4-nitrophenyl)methylsulfonamido)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (230 mg, 0.43 mmol, 29% yield) as a yellow powder. LCMS (m/z, ES+)=542 (M+H+)
Reaction SMILES: [Li]C.[CH3:3][C:4]([O:8][SiH3])=C(C)C.[CH2:10]([Si:13]1(Cl)[O:17][C:16]([CH3:19])([CH3:18])[C:15]([CH3:21])([CH3:20])[O:14]1)[CH:11]=[CH2:12]>CCCCC>[CH2:10]([Si:13]1([O:8][CH:4]=[CH2:3])[O:17][C:16]([CH3:19])([CH3:18])[C:15]([CH3:21])([CH3:20])[O:14]1)[CH:11]=[CH2:12]
Reactant: C=CC[Si]1(Cl)OC(C)(C)C(C)(C)O1
Reactant: CC(C)=C(C)O[SiH3]
Agent: [Li]C
Solvent: CCCCC
Product: C=CC[Si]1(OC=C)OC(C)(C)C(C)(C)O1
Temperature: 25 °C
Reaction time: 1 h
Yield: 72.3 %

Procedure:
To a cooled (0° C.) solution of MeLi (16.2 mL; 23 mmol; 1.4 M in Et20) was added trimethylvinyloxysilane (2.7 g; 23 mmol). The solution was warmed to room temperature and was stirred for 1 hour. The solution was cooled to −78° C., and 2-allyl-2-chloro-4,4,5,5-tetramethyl-[1,3,2]dioxasilolane (5.5 g; 25 mmol) was added. The solution was warmed to room temperature and stirred for 2 hours. The solution was diluted with pentane (20 mL), and the mixture was then filtered through a pad of celite. The filtrate was concentrated, and the residue was distilled under reduced pressure to give 3.8 g (70%) of 2-allyl-4,4,5,5-tetramethyl-2-vinyloxy-[1,3,2]dioxasilolane as a clear, colorless liquid.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:15]2[C:10](=[CH:11][C:12]([C:16]#[C:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C:25]([O:27]C)=[O:26])=[C:20]([F:29])[CH:19]=3)=[CH:13][CH:14]=2)[C:9]([CH3:31])([CH3:30])[CH2:8][CH:7]=1)=[O:5])[CH3:2].[OH-].[Li+]>C(O)C.O1CCCC1>[CH2:1]([O:3][C:4]([C:6]1[C:15]2[C:10](=[CH:11][C:12]([C:16]#[C:17][C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C:25]([OH:27])=[O:26])=[C:20]([F:29])[CH:19]=3)=[CH:13][CH:14]=2)[C:9]([CH3:30])([CH3:31])[CH2:8][CH:7]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1=CCC(C)(C)c2cc(C#Cc3ccc(CC(=O)OC)c(F)c3)ccc21
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: CCOC(=O)C1=CCC(C)(C)c2cc(C#Cc3ccc(CC(=O)O)c(F)c3)ccc21
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 27.3 %

Procedure:
A solution of 6-(3-fluoro-4-methoxycarbonylmethyl-phenylethynyl)-4,4-dimethyl-3,4-dihydro-naphthalene-1-carboxylic acid ethyl ester (Intermediate 204, 0.15 g, 0.36 mmol) in ethanol (3 mL) and tetrahydrofuran (3 mL) was treated with a 2M solution of lithium hydroxide (1.5 mL, 3 mmol) and the resulting reaction mixture was stirred at ambient temperature for 1.5 h. The volatiles were evaporated in vacuo, the residue was neutralized with saturated aqueous ammonium chloride solution and extracted with diethyl ether and ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to a residue that was purified by preparative reverse phase HPLC using 5% water in acetonitrile as the mobile phase to afford the title product (0.04 g, 27%). 1H NMR (300 MHz, CDCl3): δ 7.81 (d, J=8.2 Hz, 1H), 7.46 (d, J=1.7 Hz, 1H), 7.37 (dd, J=8.2 &1.7 Hz, 1H), 7.27-7.09 (m, 3H), 7.07 (t, J=4.8 Hz, 1H), 4.31 (q, J=7.0 Hz, 2H), 3.66 (s, 2H), 2.33 (d, J=4.8 Hz, 2H), 1.37 (t, J=7.0 Hz, 3H), 1.27 (s, 6H).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:12][CH3:13])[C:9]([OH:11])=O)=[CH:4][CH:3]=1.[NH2:14][CH2:15][C:16]1[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=1>>[C:15]([C:16]1[CH:23]=[CH:22][C:19]([CH2:20][NH:21][C:9](=[O:11])[CH:8]([C:5]2[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=2)[O:12][CH3:13])=[CH:18][CH:17]=1)#[N:14]
Reactant: N#Cc1ccc(CN)cc1
Reactant: COC(C(=O)O)c1ccc(O)cc1
Product: COC(C(=O)NCc1ccc(C#N)cc1)c1ccc(O)cc1

Procedure:
(RS)-(4-Hydroxy-phenyl)-methoxy-acetic acid was coupled with 4-aminomethyl benzonitrile according to general procedure B to give (RS)-N-(4-cyano-benzyl)-2-(4-hydroxy-phenyl)-2-methoxy-acetamide. Colorless foam. MS 295.2 ([M−H]−)
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:15]=[C:16]([S:20]([N:23]([CH2:30][P:31](=[O:34])([OH:33])[OH:32])[CH2:24][C:25]([O:27]CC)=[O:26])(=[O:22])=[O:21])[CH:17]=[CH:18][CH:19]=1.[OH-].[Li+]>O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:15]=[C:16]([S:20]([N:23]([CH2:24][C:25]([OH:27])=[O:26])[CH2:30][P:31]([OH:34])([OH:33])=[O:32])(=[O:22])=[O:21])[CH:17]=[CH:18][CH:19]=1
Reactant: CCOC(=O)CN(CP(=O)(O)O)S(=O)(=O)c1cccc(C2CN(C)Cc3c(Cl)cc(Cl)cc32)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CN1Cc2c(Cl)cc(Cl)cc2C(c2cccc(S(=O)(=O)N(CC(=O)O)CP(=O)(O)O)c2)C1
Temperature: 25 °C
Reaction time: 4 h
Yield: 34.3 %

Procedure:
Into a 50-mL round-bottom flask, was placed a solution of (3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(2-ethoxy-2-oxoethyl)phenylsulfonamido)methylphosphonic Acid (Intermediate 8.4) (180 mg, 0.33 mmol, 1.00 equiv) in tetrahydrofuran/water (5/5 mL). This was followed by the addition of lithium hydroxide (39 mg, 1.62 mmol, 4.97 equiv) in several batches at room temperature. The resulting solution was stirred for 4 h at room temperature. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The pH value of the solution was adjusted to 6 with 1M hydrogen chloride. The resulting mixture was concentrated under vacuum. The crude product (150 mg) was purified by preparative HPLC giving 59.2 mg (35%) of the title compound as a TFA salt. 1H-NMR (300 MHz, DMSO+D2O, ppm): 7.73˜7.74 (m, 1H), 7.67˜7.68 (m, 1H), 7.58˜7.62 (m, 2H), 7.49 (s, 1H), 7.00 (s, 1H), 4.71˜4.75 (m, 1H), 4.49 (d, J=16.2 Hz, 1H), 4.33 (d, J=15.9 Hz, 1H), 4.07 (s, 2H), 3.62˜3.64 (m, 1H), 3.45˜3.54 (m, 2H), 3.31˜3.40 (m, 1H), 2.88 (s, 3H). MS (ES, m/z): 523 [M+H]+.
Reaction SMILES: S(=O)(=O)(O)O.[CH2:6]([CH:12]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH2:13][OH:14])[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[Mn]([O-])(=O)(=O)=[O:24].[K+]>O.C(Cl)Cl>[CH2:6]([CH:12]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[C:13]([OH:24])=[O:14])[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: O=[Mn](=O)(=O)[O-]
Reactant: CCCCCCCCC(CO)CCCCCC
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: ClCCl
Solvent: O
Product: CCCCCCCCC(CCCCCC)C(=O)O
Temperature: 25 °C

Procedure:
Concentrated sulphuric acid (100 g) was diluted with water (750 ml) and this solution was cooled to room temperature and added to a solution of 2-hexyldecanol (242 g) in methylene chloride (600 ml). The solutions were stirred together beneath a reflux condenser and solid potassium permanganate was added in portions during 5 hours so as to maintain gentle boiling of the methylene chloride. The mixture was filtered to remove precipitated manganese dioxide, and the organic layer was separated and washed with water. The solvent was distilled leaving 2-hexyldecanoic acid (222 g) as a nearly colourless oil.
Reaction SMILES: [CH3:1][C:2]([C:20]1[CH:25]=[CH:24][C:23]([C:26](=[N:28]O)[NH2:27])=[CH:22][CH:21]=1)([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[CH:8][N:7]=1)[CH:3]([CH3:5])[CH3:4].[C:30]([O:33][CH2:34][C:35](O)=[O:36])(=[O:32])[CH3:31].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:30]([O:33][CH2:34][C:35](/[N:28]=[C:26](/[NH2:27])\[C:23]1[CH:22]=[CH:21][C:20]([C:2]([CH3:1])([C:6]2[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)=[CH:8][N:7]=2)[CH:3]([CH3:5])[CH3:4])=[CH:25][CH:24]=1)=[O:36])(=[O:32])[CH3:31]
Reactant: CC(C)C(C)(c1ccc(C(N)=NO)cc1)c1ccc(OCc2ccccn2)cn1
Reactant: CC(=O)OCC(=O)O
Agent: O=C([O-])O
Agent: On1nnc2ccccc21
Agent: [Na+]
Solvent: ClCCCl
Solvent: ClCCl
Product: CC(=O)OCC(=O)/N=C(/N)c1ccc(C(C)(c2ccc(OCc3ccccn3)cn2)C(C)C)cc1
Reaction time: 0.75 h

Procedure:
Compound 3a (350 mg, 0.896 mmol) was added to a stirred solution of acetoxyacetic acid (126 mg, 1.07 mmol), EDC (205 mg, 1.07 mmol) and HOBt (157 mg, 1.16 mmol) in DCM (7.00 mL) at rt. After approximately 45 min, the reaction mixture was poured into saturated aqueous sodium bicarbonate and extracted three times with EtOAc. The combined organic extracts were washed with water, brine, dried (sodium sulfate) and concentrated in vacuo to afford the title compound 3b, which was used without further purification in the subsequent reaction. m/z (ES) 491 (MH)+.
Reaction SMILES: [F:1][C:2]([F:36])([F:35])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]([CH:32]=[CH:33][CH:34]=2)[CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([C@@H:20]([C:26]3[CH:30]=[C:29]([CH3:31])[O:28][N:27]=3)[CH2:21][C:22]([O:24]C)=[O:23])=[CH:16][CH:15]=2)=[CH:5][CH:4]=1.[OH-].[Na+].Cl>C1COCC1.CO>[F:36][C:2]([F:1])([F:35])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:10]=[C:11]([CH:32]=[CH:33][CH:34]=2)[CH2:12][O:13][C:14]2[CH:15]=[CH:16][C:17]([C@@H:20]([C:26]3[CH:30]=[C:29]([CH3:31])[O:28][N:27]=3)[CH2:21][C:22]([OH:24])=[O:23])=[CH:18][CH:19]=2)=[CH:7][CH:8]=1
Reactant: COC(=O)C[C@@H](c1ccc(OCc2cccc(-c3ccc(C(F)(F)F)cc3)c2)cc1)c1cc(C)on1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1cc([C@@H](CC(=O)O)c2ccc(OCc3cccc(-c4ccc(C(F)(F)F)cc4)c3)cc2)no1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 39.3 (25 mg) in THF/MeOH (1:1, 4 mL) was treated with 2N aqueous NaOH solution (0.2 mL) and stirred for 2 hours at room temperature. The reaction mixture was acidified with aqueous 3N HCl while cooled with ice-water, and extracted with EtOAc to obtain 39, which was chromatographed on a silica gel column, eluting with 5˜10% MeOH in DCM. MS ESI (neg.) m/e: 480.1 (M−H). 1HNMR (CDCl3) δ 7.13 (s, 1H), 7.04 (d, 2H, J=7.27 Hz), 7.01-6.98 (m, 2H), 6.80 (s, 1H), 6.69 (d, 2H, J=Hz, J=8.62 Hz), 6.46 (d, 2H, J=8.61 Hz), 4.99 (s, 1H), 4.59 (s, 2H), 3.95 (t, 1H, J=7.60 Hz), 2.80 (m, 1H), 2.46 (m, 1H), 1.82 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[C:7]([SH:8])=[N:6][C:5]([CH3:9])=[CH:4][N:3]=1.CC1C2[O:18][CH:17]=[CH:16]C=2C=CC=1.C(OC(=O)C)(=O)C>>[CH3:1][C:2]1[C:7]([S:8][C:17](=[O:18])[CH3:16])=[N:6][C:5]([CH3:9])=[CH:4][N:3]=1
Reactant: Cc1cnc(C)c(S)n1
Reactant: Cc1cccc2ccoc12
Solvent: CC(=O)OC(C)=O
Product: CC(=O)Sc1nc(C)cnc1C

Procedure:
2,5-Dimethyl-3-acetylthio-pyrazine was prepared by acetylating 2,5-dimethyl-3-mercapto-pyrazine [compound (2) a.] with acetic anhydride in an alkaline medium according to the method described in Houben-Weyl, 4th ed., vol. 9, 753 (1955). The product has a m.p. of 36°-42°C.
Reaction SMILES: [O:1]=[O+][O-].[CH2:4]([CH:8]1[CH2:16][C:15]2[C:10](=[CH:11][C:12]([Cl:17])=[CH:13][CH:14]=2)[C:9]1=[O:18])[CH:5]=CC>ClCCl.CO>[O:1]=[CH:5][CH2:4][CH:8]1[CH2:16][C:15]2[C:10](=[CH:11][C:12]([Cl:17])=[CH:13][CH:14]=2)[C:9]1=[O:18]
Reactant: CC=CCC1Cc2ccc(Cl)cc2C1=O
Reactant: O=[O+][O-]
Solvent: ClCCl
Solvent: CO
Product: O=CCC1Cc2ccc(Cl)cc2C1=O
Reaction time: 0.75 h
Yield: 85 %

Procedure:
An ozone stream (3 g ozone/hour) was conducted for 45 minutes while stirring through a solution, cooled to -70°, of 10.3 g of (RS)-2-(2-buten-1-yl)-6-chloro-1-indanone in 200 ml of anhydrous dichloro-methane and 100 ml of anhydrous methanol. Subsequently, the mixture was flushed with oxygen for 5 minutes and with argon for 10 minutes. After the addition of 5.13 ml of dimethyl sulfide, the mixture was stirred at room temperature for 16 hours. The reaction mixture was evaporated in a vacuum. The residue was treated with 60 ml of dichoromethane and, after the addition of 15 ml of water and 15 ml of trifluoroacetic acid, stirred at room temperature for 3 hours. The mixture was subsequently poured into 150 ml of water and neutralized by the spatula-wise addition of sodium hydrogen carbonate while stirring. An additional 100 ml of water were added, the phases were separated and the aqueous phase was extracted twice with 150 ml of dichloromethane each time. The combined organic phases were dried over magnesium sulfate, concentrated in a vacuum and the crude product obtained was recrystallized from ethyl acetate/hexane. 8.29 g (85%) of (RS)-2-(2-oxoethyl)-6-chloro-1-indanone were obtained as a white solid with m.p. 80°.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH:14]([CH3:18])[CH2:15][CH2:16][OH:17])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:26][S:27](Cl)(=[O:29])=[O:28]>ClCCl>[CH3:26][S:27]([O:17][CH2:16][CH2:15][CH:14]([N:11]1[CH2:10][CH2:9][N:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:13][CH2:12]1)[CH3:18])(=[O:29])=[O:28]
Reactant: CS(=O)(=O)Cl
Reactant: CC(CCO)N1CCN(c2ccc(F)cc2)CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(CCOS(C)(=O)=O)N1CCN(c2ccc(F)cc2)CC1
Temperature: 2.5 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 3-(4-(4-fluorophenyl) piperazin-1-yl) butan-1-ol (prepared according to procedure reported in U.S. Pat. No. 5,021,420, 3.5 g, 13.87 mmol) in dichloromethane (30 ml) was added triethylamine (4.2 g, 41.61 mmol) under nitrogen atmosphere. The reaction mixture was cooled to 0-5° C. Methane sulfonyl chloride (1.58 g, 13.87 mmol) was added at 0-5° C. dropwise in 20 mins. The reaction mixture was stirred at same temp for 1 h. Progress of reaction was monitored by TLC. The reaction mixture was diluted with dichloromethane (20 ml) and washed with water (3×20 ml). The organic layer was dried over sodium sulphate and concentrated under reduced pressure to obtain title compound (4.2 g) which was used for the next reaction without further purification.
Reaction SMILES: [OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@@H:3]1[CH2:14][OH:15].CCN(CC)CC.[CH3:23][C:24]([Si:27](Cl)([CH3:29])[CH3:28])([CH3:26])[CH3:25]>ClCCl.CN(C1C=CN=CC=1)C>[Si:27]([O:15][CH2:14][C@@H:3]1[C@@H:2]([OH:1])[CH2:6][CH2:5][N:4]1[C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])([C:24]([CH3:26])([CH3:25])[CH3:23])([CH3:29])[CH3:28]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CC(C)(C)OC(=O)N1CC[C@H](O)[C@H]1CO
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CC[C@H](O)[C@H]1CO[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 99 %

Procedure:
To a 0° C. solution of (2R,3S)-tert-butyl 3-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate (1.0 equiv) and Et3N (1.05 equiv) in dichloromethane (0.5 M) was added TBSCl (1.05 equiv), followed by a few crystals of DMAP. The solution was allowed to warm to room temperature and stirred overnight. The reaction mixture was then diluted with dichloromethane, and washed with sat'd. aq. NaHCO3. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to provide the title compound (99%), which was used without further purification.
Reaction SMILES: [C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][C:4]([C:7]([C:9]2[CH2:10][CH2:11][N:12]([C:15]3[N:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[CH2:13][CH:14]=2)=[O:8])=[CH:3][CH:2]=1.[BH4-].[Na+]>CO.CCOC(C)=O>[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:2]=[CH:3][C:4]([CH:7]([C:9]2[CH2:14][CH2:13][N:12]([C:15]3[N:16]=[CH:17][CH:18]=[CH:19][N:20]=3)[CH2:11][CH:10]=2)[OH:8])=[CH:5][CH:6]=1
Reactant: O=C(C1=CCN(c2ncccn2)CC1)c1ccc(-c2ccccc2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Product: OC(C1=CCN(c2ncccn2)CC1)c1ccc(-c2ccccc2)cc1
Reaction time: 1 h
Yield: 98.4 %

Procedure:
To a solution of biphenyl-4-yl-(1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridin-4-yl)-methanone (12.2 mg, 0.0355 mmol) in methanol (0.5 ml), was added CeCl3 heptahydate (13.2 mg, 0.0355 mmol) and sodium borohydride (1.5 mg, 0.0355 mmol) at room temperature. The mixture was stirred for 1 hour and diluted with EtOAc (10 ml). The mixture was washed with water (5 ml), brine (5 ml), dried (MgSO4), filtered, and concentrated under reduced pressure to furnish the crude product. This material was purified by column chromatography (6% MeOH/CH2Cl2) to give the title compound (12 mg, 98%) as a white gel: 1H NMR (CDCl3, 400 MHz) δ 8.36 (d, J=6.4 Hz, 2H), 7.62-7.37 (m, 9H), 6.46 (t, J=6.4 Hz, 1H), 6.02 (m, 1H), 5.24 (m, 1H), 4.31 (m, 2H), 3.96 (m, 1H), 3.83 (m, 1H), 2.14 (m, 2H); MS calc'd for C22H22N3O [M+H]+: 344; Found: 344.
Reaction SMILES: [OH:1][CH2:2][CH2:3][O:4][CH2:5][N:6]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:12]([CH3:13])[C:10](=[O:11])[NH:9][C:7]1=[S:8].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(C(C)C)C(C)C)C>CN(C)C=O>[OH:1][CH2:2][CH2:3][O:4][CH2:5][N:6]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:12]([CH3:13])[C:10](=[O:11])[N:9]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:7]1=[S:8]
Reactant: Cc1c(-c2ccccc2)n(COCCO)c(=S)[nH]c1=O
Reactant: BrCc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cc1c(-c2ccccc2)n(COCCO)c(=S)n(Cc2ccccc2)c1=O
Yield: 31.4 %

Procedure:
To 2 ml of dimethylformamide, 0.62 g (2.0 mmol) of 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine, 0.26 ml (2.2 mmol) of benzyl bromide and 0.38 ml (2.2 mmol) of ethyldiisopropylamine were added and allowed to react for 5 days at room temperature under nitrogen atmosphere. The reaction mixture was concentrated under reduced pressure and the residue was adsorbed on a silica gel column and eluted with 1% methanol/chloroform to obtain 0.24 g of the target compound (Yield: 30%).
Reaction SMILES: [F:1][C:2]([F:14])([CH3:13])[CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[CH:11]=[CH:10][C:9]([NH2:12])=[N:8]1.[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1/[CH:22]=[CH:23]/[C:24](O)=[O:25]>>[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1/[CH:22]=[CH:23]/[C:24]([NH:12][C:9]1[CH:10]=[CH:11][N:7]([CH2:6][CH2:5][CH2:4][CH2:3][C:2]([F:1])([F:14])[CH3:13])[N:8]=1)=[O:25]
Reactant: O=C(O)/C=C/c1ccccc1Cl
Reactant: CC(F)(F)CCCCn1ccc(N)n1
Product: CC(F)(F)CCCCn1ccc(NC(=O)/C=C/c2ccccc2Cl)n1

Procedure:
Following general procedure B, starting from 1-(5,5-difluoro-hexyl)-1H-pyrazol-3-ylamine and (E)-3-(2-chloro-phenyl)-acrylic acid. LC-MS-conditions 05b: tR=1.13 min; [M+H]+=368.25.
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[CH2:3][S:4][C:5]1[CH:12]=[C:11]([C:13]2[C:14]([C:18]([F:21])([F:20])[F:19])=[N:15][NH:16][CH:17]=2)[CH:10]=[CH:9][C:6]=1[CH:7]=O.[C:24](=O)([O-])[O-].[K+].[K+].O1CCOCC1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[F:1][C:2]([F:23])([F:22])[CH2:3][S:4][C:5]1[CH:12]=[C:11]([C:13]2[C:14]([C:18]([F:21])([F:20])[F:19])=[N:15][NH:16][CH:17]=2)[CH:10]=[CH:9][C:6]=1[CH:7]=[CH2:24]
Reactant: O=Cc1ccc(-c2c[nH]nc2C(F)(F)F)cc1SCC(F)(F)F
Reactant: O=C([O-])[O-]
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: C=Cc1ccc(-c2c[nH]nc2C(F)(F)F)cc1SCC(F)(F)F
Temperature: 25 °C
Yield: 43.6 %

Procedure:
2.83 g (8.0 mmol) of 2-(2,2,2-trifluoroethylthio)-4-(3-trifluoromethylpyrazolyl)benzaldehyde (Compound No. V-275 of the present invention) prepared in the same-manner as in Example 8 (9), 2.85 g (8.0 mmol) of methyltriphenylphosphonium bromide and 1.38 g (10.0 mmol) of potassium carbonate were refluxed in a solvent mixture of 20 ml of dioxane and 0.3 ml of water with heating for 5 hours. After cooling down to room temperature, the insolubles were filtered off, and the dioxane was distilled off under reduced pressure. Purification of the residue by silica gel column chromatography afforded 1.23 g of [2-ethenyl-5-(3-trifluoromethylpyrazolyl)phenyl] 2,2,2-trifluoroethyl sulfide (yield 43.8%) as a pale yellow liquid (nD20 1.5328).