Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si:1]([O:8]S(C(F)(F)F)(=O)=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Br:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2(O)[CH2:26][CH2:25][CH2:24]2)=[CH:19][CH:18]=1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>ClCCl>[Br:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:26][CH2:25][CH2:24]2)=[CH:19][CH:18]=1
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: OC1(c2ccc(Br)cc2)CCC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](C)(C)OC1(c2ccc(Br)cc2)CCC1
Temperature: 25 °C
Yield: 92.7 %

Procedure:
TBSOTf (360 μL, 1.57 mmol) was added to a 0° C. solution of 3-1 (235 mg, 1.04 mmol) and triethylamine (450 μL, 3.23 mmol) in dichloromethane (3 mL). The reaction was allowed to warm to room temperature and after 1 h, saturated NaHCO3 solution was added. The resulting mixture was extracted with ethyl acetate (3×30 mL) and the combined ethyl acetate solution was washed with brine. The solution was then dried (Na2SO4), filtered and evaporated. Purification by flash chromatography on silica gel (hexanes) gave 3-2 (329 mg, 93%).
Reaction SMILES: [Br-].[CH3:2]P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Li]CCCC.[CH3:27][C:28]1[N:33]=[C:32]([C:34]([C:36]2[N:37]=[CH:38][N:39]([C:41]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH:40]=2)=O)[CH:31]=[CH:30][CH:29]=1.CCOCC>C1COCC1>[CH3:27][C:28]1[CH:29]=[CH:30][CH:31]=[C:32]([C:34]([C:36]2[N:37]=[CH:38][N:39]([C:41]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH:40]=2)=[CH2:2])[N:33]=1
Reactant: Cc1cccc(C(=O)c2cn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cn2)n1
Reactant: C[PH](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOCC
Product: C=C(c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1)c1cccc(C)n1
Temperature: -50 °C
Yield: 50 %

Procedure:
Methyl triphenylphosphine bromide (commercially available from Aldrich) (2.2 g, 6.16, mmol) in THF(60 mL) at −70° C. was treated with nBuLi (2.44 mL, 2.5M in hexane). The reaction mixture warmed to −50° C. in 1 h. A solution of (6-methyl-pyridin-2-yl)-(1-trityl-1H-imidazol-4-yl)-methanone (Intermediate D3) (1.38 g, 3.2 mmol) in THF (25 mL) was added to the mixture via syringe at −50° C. The mixture was allowed to warm to rt for 1.5 h. The mixture was poured into ether (mL) and washed with water (2×10 mL). The organic solution was dried over MgSO4, filtered and evaporated to leave a residue. This was purified by chromatography on SiO2 with diethyl ether to give 2-methyl-6-[1-(1-trityl-1H-imidazol-4-yl)-vinyl]-pyridine (Intermediate D4) 0.68 g (50%).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([CH2:9][N:10]2[CH2:15][CH2:14][CH:13]([CH2:16][C:17]([C:19]3[S:20][CH:21]=[CH:22][C:23]=3Br)=[O:18])[CH2:12][CH2:11]2)=[CH:7][CH:6]=[CH:5][N:4]=1.[C:25]1(OB(O)O)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CO.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.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.O>[CH3:1][O:2][C:3]1[C:8]([CH2:9][N:10]2[CH2:15][CH2:14][CH:13]([CH2:16][C:17](=[O:18])[C:19]3[S:20][CH:21]=[CH:22][C:23]=3[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:12][CH2:11]2)=[CH:7][CH:6]=[CH:5][N:4]=1
Reactant: COc1ncccc1CN1CCC(CC(=O)c2sccc2Br)CC1
Reactant: OB(O)Oc1ccccc1
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: [Na+]
Solvent: CO
Solvent: Cc1ccccc1
Solvent: O
Product: COc1ncccc1CN1CCC(CC(=O)c2sccc2-c2ccccc2)CC1
Yield: 100.7 %

Procedure:
290 mg of 1-[(2-methoxy-3-pyridyl)methyl]-4-[2-(3-bromo-2-thienyl)-2-oxoethyl]piperidine obtained in Example 73, 173 mg of phenylboric acid and 42 mg of tetrakis(triphenylphosphine)palladium were suspended in 5.6 ml of toluene, 1.4 ml of methanol and 2.8 ml of 2 M sodium carbonate, and the mixture was heated under reflux for 3 hours under nitrogen flow. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the crude product was purified by silica gel column chromatography (ethyl acetate), to give 290 mg of the title compound as a yellow oil.
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[O:9][CH2:10][CH3:11].CC1(C)CCCC(C)(C)N1.C([Li])CCCCC.[CH:29](=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CCCCCC.C1COCC1>[F:8][C:7]1[C:2]([F:1])=[C:3]([O:9][CH2:10][CH3:11])[CH:4]=[CH:5][C:6]=1[CH:29]([OH:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: O=Cc1ccccc1
Reactant: CCOc1cccc(F)c1F
Agent: CC1(C)CCCC(C)(C)N1
Agent: [Li]CCCCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCOc1ccc(C(O)c2ccccc2)c(F)c1F

Procedure:
1.1 kg/h of a 1 M solution of 2,3-difluorophenetole containing 10 mol % of 2,2,6,6-tetramethylpiperidine were introduced into a continuous-flow reactor and mixed with 0.4 kg/h of a 2.5 M solution of hexyllithium in hexane at −35° C. After the mixture had passed through the reaction zone, 0.28 kg/h of a 4.7 M solution of benzaldehyde in THF was mixed in. After the reaction had finished, the product was collected and worked up in the customary manner, giving 2,3-difluoro-4-ethoxy-α-phenylbenzyl alcohol. The conversion based on the starting compound was 97%.
Reaction SMILES: [OH:1][C:2]1[C:3]([C:15]([O:17]C)=[O:16])=[N:4][N:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6](=[O:8])[CH:7]=1.Cl>[OH-].[Na+]>[OH:1][C:2]1[C:3]([C:15]([OH:17])=[O:16])=[N:4][N:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6](=[O:8])[CH:7]=1
Reactant: COC(=O)c1nn(-c2ccccc2)c(=O)cc1O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)c1nn(-c2ccccc2)c(=O)cc1O
Temperature: 25 °C
Yield: 79.8 %

Procedure:
Methyl 4-hydroxy-6-oxo-1-phenyl-1,6-dihydropyridazine-3-carboxylate (0.8 g, 3.24 mmol) was suspended in sodium hydroxide solution (20 ml of 2.0M) and heated at reflux for 1 hour. The mixture was allowed to cool to room temperature, acidified with 2M hydrochloric acid and extracted with ethyl acetate (3×15 ml). The combined organic extracts were dried over anhydrous magnesium sulphate, filtered and evaporated to yield 4-hydroxy-6-oxo-1-phenyl-1,6-dihydropyridazine-3-carboxylic acid as a yellow solid (0.6 g, 80%).
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][C:5]2[O:6][C:7]3[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=3[CH:9]=[N:10][C:4]=2[CH:3]=1.[C:17]1(=[O:27])[O:22][C:20](=[O:21])[C:19]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:18]12>C1COCC1>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]2[O:6][C:7]3[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=3[CH2:9][N:10]([C:17]([C:18]3[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=3[C:20]([OH:22])=[O:21])=[O:27])[C:4]=2[CH:3]=1
Reactant: Clc1ccc2c(c1)N=Cc1ccccc1O2
Reactant: O=C1OC(=O)c2ccccc21
Solvent: C1CCOC1
Product: O=C(O)c1ccccc1C(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21
Yield: 70.3 %

Procedure:
A stirred mixture of 8-chloro-dibenz[b,f]-[1,4]oxazepine (3.35 g) and phthalic anhydride (2.13 g) in THF (40 mL) was heated to reflux for 4 days. The mixture was concentrated and the residue was triturated with ether. The precipitated solid was filtered to give the title compound as a white solid (3.84 g).
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([CH2:19]O)[CH:18]=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)([Cl:23])=O>ClCCl>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([CH2:19][Cl:23])[CH:18]=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=S(Cl)Cl
Reactant: O=S(=O)(c1ccccc1)n1ccc2cc(CO)cnc21
Solvent: ClCCl
Product: O=S(=O)(c1ccccc1)n1ccc2cc(CCl)cnc21
Reaction time: 2 h
Yield: 73.7 %

Procedure:
To a stirred solution of (1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-methanol (4.2 g, 14.6 mmol) in dichloromethane (20 mL) at 0° C. was added a solution of thionyl chloride (1.6 mL, 21.9 mmol) in dichloromethane (5 mL) and then stirred for 2 h. The reaction mixture was concentrated in vacuo and the residue was extracted with ethyl acetate, washed with a saturated aqueous sodium bicarbonate solution (2×100 mL), brine, dried over anhydrous sodium sulfate and then concentrated in vacuo to afford 1-benzenesulfonyl-5-chloromethyl-1H-pyrrolo[2,3-b]pyridine (3.3 g, 75%) as a light yellow solid which was used in the next step without further purification: LC/MS m/e calcd for C14H11ClN2O2S [M+H]+ 307.77, observed 307.1.
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][C:6]1([CH2:13][N+:14]([O-])=O)[CH2:10][CH2:9][C:8]([CH3:12])([CH3:11])[CH2:7]1)C>[Ni].CO>[CH3:11][C:8]1([CH3:12])[CH2:9][CH2:10][C:6]2([CH2:13][NH:14][C:4](=[O:3])[CH2:5]2)[CH2:7]1
Reactant: CCOC(=O)CC1(C[N+](=O)[O-])CCC(C)(C)C1
Agent: [Ni]
Solvent: CO
Product: CC1(C)CCC2(CNC(=O)C2)C1
Reaction time: 24 h
Yield: 91.9 %

Procedure:
The ester 3 (380 mg, 1.6 mmol) and Raney Nickel (1 g) were suspended in methanol (75 mL) and shaken under a hydrogen atmosphere for 24 hours. The catalyst was removed by filtration, the filtrate concentrated to give the lactam 4 (246 mg, 94%) as a white solid.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10][CH2:11][CH:12]([C:19]([O:21]CC)=O)[CH2:13][C:14]([O:16]CC)=O.[CH:24]1([NH2:30])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1>C1(C)C=CC=CC=1>[CH:24]1([NH:30][C:14]([CH2:13][CH:12]([C:19]([NH:3][CH:4]2[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]2)=[O:21])[CH2:11][S:10][C:2]2[S:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)=[O:16])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1
Reactant: CCOC(=O)CC(CSc1nc2ccccc2s1)C(=O)OCC
Reactant: NC1CCCCC1
Solvent: Cc1ccccc1
Product: O=C(CC(CSc1nc2ccccc2s1)C(=O)NC1CCCCC1)NC1CCCCC1

Procedure:
18.5 parts of diethyl 3-(benzothiazol-2-ylthio)-propane- 1,2-dicarboxylate are stirred with 31.1 parts cyclohexylamine for 12 hours at 95° C. The mixture is cooled and toluene added with stirring. The resulting solid is filtered off, washed with toluene and dried to give N,N'-dicyclohexyl 3-(benzothiazol-2-ylthio)-1,2-propane dicarboxylic acid diamide, melting at 147°-49° C.
Reaction SMILES: [CH3:1][C:2]([CH3:22])([CH3:21])[CH2:3][CH2:4][C:5]1[CH:6]=[C:7]([C:12]2[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=2[F:20])[CH:8]=[CH:9][C:10]=1[OH:11].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:42]1([CH:45]([C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([CH2:58]O)[CH:53]=2)[CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48])[CH2:44][CH2:43]1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1.C1(C)C=CC=CC=1>[CH:42]1([CH:45]([C:52]2[CH:57]=[CH:56][CH:55]=[C:54]([CH2:58][O:11][C:10]3[CH:9]=[CH:8][C:7]([C:12]4[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=4[F:20])=[CH:6][C:5]=3[CH2:4][CH2:3][C:2]([CH3:22])([CH3:21])[CH3:1])[CH:53]=2)[CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48])[CH2:44][CH2:43]1
Reactant: CCOC(=O)CC(c1cccc(CO)c1)C1CC1
Reactant: COc1ccc(F)c(-c2ccc(O)c(CCC(C)(C)C)c2)c1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CCOC(=O)CC(c1cccc(COc2ccc(-c3cc(OC)ccc3F)cc2CCC(C)(C)C)c1)C1CC1
Yield: 48.3 %

Procedure:
To a solution of 3-(3,3-dimethylbutyl)-2′-fluoro-5′-methoxy-[1,1′-biphenyl]-4-ol (200 mg) in THF (5.0 mL) were added triphenylphosphine (260 mg), ethyl 3-cyclopropyl-3-(3-(hydroxymethyl)phenyl)propanoate (246 mg) and a 40% solution of diethyl azodicarboxylate in toluene (400 μL), and the reaction mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (170 mg) as a colorless oil.
Reaction SMILES: [CH3:1][CH:2]1[CH2:4][N:3]1[P:5](=[O:20])([O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:21]1([Mg]Cl)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>Cl[Cu].C1COCC1>[C:21]1([CH2:4][CH:2]([NH:3][P:5](=[O:20])([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[O:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH3:1])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: Cl[Mg]c1ccccc1
Reactant: CC1CN1P(=O)(Oc1ccccc1)Oc1ccccc1
Agent: Cl[Cu]
Solvent: C1CCOC1
Product: CC(Cc1ccccc1)NP(=O)(Oc1ccccc1)Oc1ccccc1
Temperature: 48 °C
Reaction time: 2 h
Yield: 72 %

Procedure:
A 100 mL, 3-necked flask equipped with an overhead stirrer, reflux condenser and pressure equalizing addition funnel was charged with 2b (10.0 g, 34.6 mmol), THF (50 mL) and CuCl (42 mg, 1 mol %) and the stirrer was started. The stirred mixture was heated to 48° C. and the pressure equalizing addition funnel was charged with PhMgCl (2M in THF, 17.4 mL). This solution was added slowly while maintaining a reaction temperature of 48-51° C. The reaction was allowed to stir at 48-51° C. for an additional 2 hours until the GC analysis indicated the consumption of 2b (<1.0%) and the reaction mixture was cooled to ambient temperature. The reaction was quenched by slow addition to a cooled solution of saturated aqueous ammonium chloride/water mixture (50/50 v/v, 60 mL) while maintaining the batch temperature below 20° C. Heptanes (60 mL) was used to rinse the reactor and was transferred to the quench mixture. The biphasic mixture was agitated for 15 minutes and the aqueous layer was removed. The organic layer washed with deionized water (20 mL) and the organic phase concentrated under reduced pressure to give viscous oil. This residue was dissolved in heptanes (50 mL) and the solution was concentrated under reduced pressure. The residue was crystallized from ethanol (1 g/5 mL) to give 6b as a white solid (9.05 g, 72% yield, 99.85% GC purity containing 0.05% of 8b). Mp 102-103° C. (lit1 101-102° C.). 1H NMR (300 MHz, CDCl3) δ 7.38-7.11 (m, 15H), 3.83-3.65 (m, 1H), 3.00-2.89 (m, 1H), 2.86-2.78 (m, 1H), 2.73-2.62 (m, 1H), 1.15 (d, J=10.1 Hz, 3H).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[CH:11]=[C:12]([CH:15]=[CH:16][C:17]=3[O:18][CH3:19])[CH:13]=[O:14])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].[CH3:22]I.O>CN(C=O)C>[CH3:22][N:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[CH:11]=[C:12]([CH:15]=[CH:16][C:17]=3[O:18][CH3:19])[CH:13]=[O:14])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: CI
Reactant: COc1ccc(C=O)cc1-c1ccc2[nH]ccc2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc(C=O)cc1-c1ccc2c(ccn2C)c1
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 90.5 %

Procedure:
A solution of 3-(indol-5-yl)-4-methoxybenzaldehyde (0.50 g, 2.0 mmol) in DMF (10 mL) was cooled to 0° C. and NaH (60% dispersion in mineral oil, 0.14 g, 3.0 mmol) was added. The mixture was stirred at 0° C. for 45 minutes, then methyl iodide (0.34 g, 4.4 mmol) was added and the reaction was stirred for 16 hours at room temperature. The mixture was then poured into water and extracted with ethyl acetate, washed with water and dried over sodium sulphate. The solvent was removed in vacuo and the crude was purified by column chromatography (hexane/ethyl acetate 7/3) to give 0.48 g of title compound.
Reaction SMILES: [C:1]([N:5]=[N:6][C:7](Cl)([CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[C:15]([O:19][OH:20])([CH3:18])([CH3:17])[CH3:16].[OH-].[Na+]>CO>[C:1]([N:5]=[N:6][C:7]([O:20][O:19][C:15]([CH3:18])([CH3:17])[CH3:16])([CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH3:8])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)CC(C)(Cl)N=NC(C)(C)C
Reactant: CC(C)(C)OO
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)CC(C)(N=NC(C)(C)C)OOC(C)(C)C

Procedure:
The 2-t-butylazo-2-(t-butylperoxy)-4,4-dimethylpentane was prepared in 78% crude yield from 3.36 grams (.02moles) of 2-t-butylazo-2-chloro-4,4-dimethylpentane, 2.77 grams (.0277 moles) of 90% t-butyl hydroperoxide and 2.0 grams (.025 moles) of 50% NaOH in 20 ml. of methanol. The procedure was the same as that described in Example X.
Reaction SMILES: [Si]([O:8][CH2:9][CH2:10][CH2:11][NH:12][S:13]([C:16]1[CH:21]=[C:20]([F:22])[C:19]([CH2:23][S:24][C:25]2[N:26]([C:42]3[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=3)[C:27]([C:30]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[C:35]([O:40][CH3:41])[CH:34]=3)([CH3:32])[CH3:31])=[CH:28][N:29]=2)=[C:18]([Cl:49])[CH:17]=1)(=[O:15])=[O:14])(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:49][C:18]1[CH:17]=[C:16]([S:13]([NH:12][CH2:11][CH2:10][CH2:9][OH:8])(=[O:15])=[O:14])[CH:21]=[C:20]([F:22])[C:19]=1[CH2:23][S:24][C:25]1[N:26]([C:42]2[CH:43]=[CH:44][C:45]([F:48])=[CH:46][CH:47]=2)[C:27]([C:30]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[C:35]([O:40][CH3:41])[CH:34]=2)([CH3:31])[CH3:32])=[CH:28][N:29]=1
Reactant: COc1cc(C(C)(C)c2cnc(SCc3c(F)cc(S(=O)(=O)NCCCO[Si](C)(C)C(C)(C)C)cc3Cl)n2-c2ccc(F)cc2)ccc1F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: COc1cc(C(C)(C)c2cnc(SCc3c(F)cc(S(=O)(=O)NCCCO)cc3Cl)n2-c2ccc(F)cc2)ccc1F
Reaction time: 2 h
Yield: 98.7 %

Procedure:
To a solution of N-(3-(tert-butyldimethylsilyloxy)propyl)-3-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)benzenesulfonamide (1.08 g, 1.44 mmol) in THF (10 mL) was added TBAF (1.0M in THF, 0.7 mL, 1.39 mmol). After stirring 2 h, the reaction was quenched with AcOH (1 mL) and then evaporated in vacuo. The residue was purified by column chromatography (Hex/EtOAc=1:2) to give 3-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-N-(3-hydroxypropyl)benzenesulfonamide (0.91 g, 99%). 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J=1.11 Hz, 1H), 7.43 (dd, J=8.41, 1.71 Hz, 1H), 7.15 (s, 1H), 6.56 (dd, J=8.17, 2.21 Hz, 1H), 6.48 (ddd, J=4.63, 3.53, 1.95 Hz, 3H), 3.93 (d, J=1.24 Hz, 2H), 3.78 (s, 3H), 3.64 (t, J=5.63 Hz, 2H), 3.29-3.19 (m, 2H), 1.77-1.69 (m, 2H), 1.51 (s, 7H), 1.30-1.23 (m, 1H), 5.41-5.23 (m, 1H), 6.87 (ddd, J=10.85, 9.87, 5.32 Hz, 3H).
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]([N+:12]([O-])=O)[C:9]([NH2:15])=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([CH2:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:7]2.[C:25](O)(=[O:29])[C:26](O)=[O:27]>Cl>[Br:1][C:2]1[C:3]2[CH2:4][CH2:5][N:6]([CH2:16][CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:7][C:8]=2[C:9]2[NH:15][C:25](=[O:29])[C:26](=[O:27])[NH:12][C:10]=2[CH:11]=1
Reactant: O=C(O)C(=O)O
Reactant: Nc1c([N+](=O)[O-])cc(Br)c2c1CN(CCCc1ccccc1)CC2
Agent: Cl
Product: O=c1[nH]c2cc(Br)c3c(c2[nH]c1=O)CN(CCCc1ccccc1)CC3
Yield: 60.3 %

Procedure:
A solution of the product from Example 12 (0.98 g, 2.72 mmol) in 3N HCl (35 mL) was treated with oxalic acid (0.36 g, 2.86 mmol) and refluxed for five hours. When cool to room temperatures the precipitate was filtered, suspended in water (70 mL) and basifyed to pH 8. The solids were filtered, and dried to give the title compound (0.68 g, 60%) as a brown solid, mp=288-293° C.
Reaction SMILES: [C:1]([O:4][C@@:5]1([CH3:25])[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:21]([CH2:22][CH2:23][C@:6]12[CH3:7])[C@:19]1([CH3:20])[C:14](=[CH:15][C:16](=[O:24])[CH2:17][CH2:18]1)[CH:13]=[CH:12]3)(=[O:3])[CH3:2].[C-:26]#[N:27].C([Al+]CC)C.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:1]([O:4][C@@:5]1([CH3:25])[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:21]([CH2:22][CH2:23][C@:6]12[CH3:7])[C@:19]1([CH3:20])[C:14](=[CH:15][C:16](=[O:24])[CH2:17][CH2:18]1)[CH2:13][C@H:12]3[C:26]#[N:27])(=[O:3])[CH3:2]
Reactant: [C-]#N
Reactant: CC(=O)O[C@@]1(C)CC[C@H]2[C@@H]3C=CC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
Agent: CC[Al+]CC
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CC(=O)O[C@@]1(C)CC[C@H]2[C@@H]3[C@H](C#N)CC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
Temperature: 25 °C
Reaction time: 24 h
Yield: 70.5 %

Procedure:
At room temperature, 17.1 g of 17β-acetoxy-17α-methylandrosta-4,6-dien-3-one [U.S. Pat. No. 3,033,752 (1962)] in 170 ml of toluene is combined with 100 ml of diethyl aluminum cyanide solution (1 mole in toluene). After 24 hours, the reaction mixture is introduced into a potassium sodium tartrate solution, diluted with ethyl acetate, and the mixture is stirred for 1 hour at room temperature, extracted with ethyl acetate, the organic phase is washed with water, dried, and concentrated under vacuum. The resultant crude product is allowed to react in 500 ml of methanol at room temperature with 360 mg of potassium carbonate, the mixture is concentrated under vacuum after 2.5 hours, diluted with ethyl acetate, washed with water, and dried. After the crude product has been chromatographed on silica gel with a methylene chloride (tert-butyl methyl ether) gradient, 13 g of 17β-acetoxy-17α-methyl-3-oxoandrost-4-ene-7α-carbonitrile is obtained, mp 211°-216° C. (from isopropyl ether).
Reaction SMILES: [OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.Br[C:37]1[CH:38]=[CH:39][C:40]2[N:41]([N:43]=[C:44]([O:46][CH3:47])[N:45]=2)[CH:42]=1>>[OH:1][C:2]([CH3:34])([CH3:35])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([C:37]3[CH:38]=[CH:39][C:40]4[N:41]([N:43]=[C:44]([O:46][CH3:47])[N:45]=4)[CH:42]=3)=[CH:17][CH:18]=2)[CH3:12])[CH2:6][CH2:5]1
Reactant: C[C@@H](c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
Reactant: COc1nc2ccc(Br)cn2n1
Product: COc1nc2ccc(-c3ccc([C@H](C)N4CC[C@](CC(C)(C)O)(c5ccccc5)OC4=O)cc3)cn2n1
Yield: 66 %

Procedure:
The title compound was prepared from (5)-6-(2-hydroxy-2-methyl-propyl)-6-phenyl-3-{(S)-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-ethyl}-[1,3]oxazinan-2-one and 6-bromo-2-methoxy-[1,2,4]triazolo[1,5-a]pyridine following a procedure analogous to that described in EXAMPLE 7. Yield: 66% of theory; Mass spectrum (ESI+): m/z=501 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 0.81 (s, 3H), 1.19 (s, 3H), 1.48 (d, J=7.0 Hz, 3H), 2.03 (s, 2H), 2.13-2.22 (m, 1H), 2.38-ca. 2.53 (m, 2H) superimposed on DMSO-d5, 3.00-3.07 (m, 1H), 4.04 (s, 3H), 4.23 (s, 1H), 5.44 (q, J=7.0 Hz, 1H), 6.98 (d, J=8.2 Hz, 2H), 7.27-7.40 (m, 5H), 7.51 (dm, J=8.2 Hz, 2H), 7.67 (d, J=9.2 Hz, 1H), 7.82 (dd, J=9.2, 1.8 Hz, 1H), 9.05 (hardly resolved d, 1H).