Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10]([C:28](O)=[O:29])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:31]([O:38][CH2:39][CH2:40][NH:41][CH:42]1[CH2:45][O:44][CH2:43]1)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O.O>[Si:31]([O:38][CH2:39][CH2:40][N:41]([CH:42]1[CH2:45][O:44][CH2:43]1)[C:28]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:14]([OH:15])[N:13]=[C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:18][CH2:19][CH2:20][CH2:21]2)[N:11]=1)=[O:29])([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]
Reactant: O=C(O)c1nc(CC2(c3ccccc3)CCCC2)nc(O)c1OCc1ccccc1
Reactant: CC(C)(C)[Si](C)(C)OCCNC1COC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: CC(C)(C)[Si](C)(C)OCCN(C(=O)c1nc(CC2(c3ccccc3)CCCC2)nc(O)c1OCc1ccccc1)C1COC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.6 %

Procedure:
To a stirred solution mixture of 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid (283) (158 mg, 0.39 mmol) and [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-oxetan-3-yl-amine (8 g) (104 mg, 0.47 mmol) in dimethylformamide (3 mL) were added N,N-diisopropylethylamine (0.2 mL, 1.17 mmol) and HATU (222 mg, 0.59 mmol). The reaction mixture was stirred at room temperature for 1 h, followed by the addition of water (50 mL). the mixture was extracted with ethyl acetate (3×20 mL) and the combined organic part was washed with water (3×50 mL) and brine (2×30 mL) and dried and concentrated. The crude product was purified by Combi-Flash column (eluted at 20-30% ethyl acetate in hexane) to get 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-oxetan-3-yl-amide (296) (240 mg, 99.43%) as a yellow gummy mass.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[N:9]=[C:8]([C:10]2[CH:11]=[C:12]([C:16]3([C:22]([OH:24])=[O:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[CH:13]=[CH:14][CH:15]=2)[CH:7]=[C:6]([NH:25][CH2:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=2)[N:5]=1.[CH3:39]O>>[CH3:39][O:23][C:22]([C:16]1([C:12]2[CH:13]=[CH:14][CH:15]=[C:10]([C:8]3[CH:7]=[C:6]([NH:25][CH2:26][CH2:27][C:28]4[CH:29]=[CH:30][C:31]([O:34][C:35]([F:37])([F:38])[F:36])=[CH:32][CH:33]=4)[N:5]=[C:4]([O:3][CH3:2])[N:9]=3)[CH:11]=2)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)=[O:24]
Reactant: CO
Reactant: COc1nc(NCCc2ccc(OC(F)(F)F)cc2)cc(-c2cccc(C3(C(=O)O)CCOCC3)c2)n1
Agent: Cl
Product: COC(=O)C1(c2cccc(-c3cc(NCCc4ccc(OC(F)(F)F)cc4)nc(OC)n3)c2)CCOCC1
Temperature: 70 °C
Reaction time: 8 h

Procedure:
Hydrogen chloride (4 M in 1,4-dioxane, 43.5 μL, 0.17 mmol) is added to a solution of N-[4-(3-{2-methoxy-6-[2-(4-trifluoromethoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-phenyl)-tetrahydro-pyran-4-carboxylic acid (45 mg, 0.09 mmol) in methyl alcohol (4 mL) and the reaction mixture is stirred overnight at 70° C. The reaction is cooled to room temperature, quenched with water. The volatiles are removed in vacuo. The aqueous is extracted twice with ethyl acetate. The combined extracts are dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by chromatography (SiO2 packed column), eluted with ethyl acetate/heptane to afford 4-(3-{2-methoxy-6-[2-(4-trifluoromethoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-phenyl)-tetrahydro-pyran-4-carboxylic acid methyl ester [86 mg, Example 84(b)]. LCMS: RT=2.48 minutes, MS: 532 (M+H). IC50=70 nM
Reaction SMILES: [Cl:1][C:2]1[C:11]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[C:10]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[CH:9]=[C:8]2[C:3]=1[C:4](=[O:37])[C:5]([C:34]([OH:36])=O)=[CH:6][N:7]2[CH2:32][CH3:33].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[N:71]1([CH2:76][CH2:77][NH2:78])[CH2:75][CH2:74][CH2:73][CH2:72]1>CN(C)C=O>[Cl:1][C:2]1[C:11]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[C:10]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=2)[CH:9]=[C:8]2[C:3]=1[C:4](=[O:37])[C:5]([C:34]([NH:78][CH2:77][CH2:76][N:71]1[CH2:75][CH2:74][CH2:73][CH2:72]1)=[O:36])=[CH:6][N:7]2[CH2:32][CH3:33]
Reactant: NCCN1CCCC1
Reactant: CCn1cc(C(=O)O)c(=O)c2c(Cl)c(OCc3ccc(OC)cc3)c(OCc3ccc(OC)cc3)cc21
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCn1cc(C(=O)NCCN2CCCC2)c(=O)c2c(Cl)c(OCc3ccc(OC)cc3)c(OCc3ccc(OC)cc3)cc21
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 66.9 %

Procedure:
To a solution of 5-chloro-1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (Example 16f) (5 g, 8.68 mmol) in N,N-Dimethylformamide (DMF) (75 mL) was added HATU (3.96 g, 10.42 mmol) and DIPEA (4.55 mL, 26.1 mmol), the resulting mixture was stirred at r.t. for 15 min. Then 2-(pyrrolidin-1-yl)ethanamine (1.502 mL, 9.55 mmol) was added and the resulting mixture was stirred at r.t. for 1 h. The mixture was concentrated and partitioned between water and DCM. The organic layer was separated and washed with water (2×), sat. NaHCO3 (aq.) and brine. The organic solution was dried over Na2SO4, and concentrated. The residue was purified by automated silica gel chromatography (CombiFlash Rf) eluting with MeOH/DCM (0-25%), followed by reverse phase chromatography (CombiFlash Rf) eluting with ACN/water (0-100%) to afford 5-chloro-1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinoline-3-carboxamide (3.6 g, 5.81 mmol, 66.9% yield) as a white solid. LCMS: (M+H)+: 620.5
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[N:12]=[CH:11][CH:10]=[C:9]2[CH3:14])([O-])=O.O.NN>CO>[NH2:1][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[N:12]=[CH:11][CH:10]=[C:9]2[CH3:14]
Reactant: Cc1ccnc2c([N+](=O)[O-])cccc12
Agent: NN
Solvent: CO
Solvent: O
Product: Cc1ccnc2c(N)cccc12
Reaction time: 1 h
Yield: 99.3 %

Procedure:
To a stirred mixture of 8-nitro-4-methylquinoline (250 mg), ferric chloride hexahydrate (7.18 mg) and activated carbon (38 mg) in methanol was added hydrazine monohydrate (266 mg) at 65° C., and the mixture was stirred for 1 hour at the same temperature. Insoluble material was filtered off, and the filtrate was concentrated in vacuo The mixture was dissolved in ethyl acetate, washed with brine, dried over magnesium sulfate and evaporated in vacuo to give 8-amino-4-methylquinoline (208.8 mg).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].O1CCCC1.[O:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]1[O:18][C:19]1[CH:28]=[CH:27][C:22]([C:23](OC)=[O:24])=[CH:21][CH:20]=1>O>[O:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]1[O:18][C:19]1[CH:20]=[CH:21][C:22]([CH2:23][OH:24])=[CH:27][CH:28]=1
Reactant: COC(=O)c1ccc(OC2CCCCO2)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: OCc1ccc(OC2CCCCO2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 71.1 %

Procedure:
To a mechanically stirred slurry of 10 g of lithium aluminum hydride and 100 mL of tetrahydrofuran was added dropwise with cooling in an ice bath a solution of 32.9 g (0.139 mol) of methyl 4-tetrahydropyranyloxybenzoate at a rate such that the temperature did not exceed 30° C. After stirring 18 hr at room temperature, the solution was treated cautiously with 100 mL of water. The mixture was filtered, and the filtrate was stirred with 200 mL of aqueous sodium hydroxide for 2 hr. The organic layer was separated and evaporated with a rotary evaporator. The residue was dissolved in 200 mL of ether and washed three times with 5% aqueous sodium bicarbonate and dried over sodium sulfate. Evaporation gave 20.58 g of 4-tetrahydropyranyloxybenzyl alcohol as a liquid. 1H NMR (360 MHz, THF-d8): 1.45-2.0 (m's, 6H, CH2), 3.5 (m, 1H, OCH2), 3.8 (m, 1H, OCH2 ), 4.25 (t, J=6, 1H, OH), 4.45 (d, J=6, 2H, ArCH2OH), 5.35 (t, J=3, 1H, OCHO), 6.95 (d, J=8, 2H, ArH), 7.19 (d, J=8, 2H, ArH).
Reaction SMILES: [CH3:1][C:2]([OH:7])([CH2:5][CH3:6])[CH2:3][CH3:4].CN(C)C1C=CC=CC=1.[Br:17][CH2:18][C:19](Br)=[O:20].O>ClCCl>[Br:17][CH2:18][C:19]([O:7][C:2]([CH2:5][CH3:6])([CH3:1])[CH2:3][CH3:4])=[O:20]
Reactant: CCC(C)(O)CC
Reactant: O=C(Br)CBr
Solvent: CN(C)c1ccccc1
Solvent: ClCCl
Solvent: O
Product: CCC(C)(CC)OC(=O)CBr
Temperature: 25 °C
Reaction time: 2 h
Yield: 88.8 %

Procedure:
To a solution of 3-methyl-3-pentanol (10.6 g, 103 mmol) in dichloromethane (49 ml), N,N-dimethylaniline (15.0 g, 124 mmol) and bromoacetyl bromide (25.0 g, 124 mmol) were added and stirred at room temperature for 2 hours under a nitrogen stream. The reaction mixture was poured into water, extracted with tert-butyl methyl ether, washed sequentially with saturated aqueous potassium bisulfate and saturated aqueous sodium bicarbonate, and then dried over sodium sulfate. After evaporation under reduced pressure to remove the solvent, the resulting residue was purified by vacuum distillation (5 mmHg, 71° C. to 72° C.) to give the titled compound (20.4 g, 89%) as a colorless oil.
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[CH2:13]([C:17]1[N:21]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[C:30]([C:35]#[N:36])=[CH:31][CH:32]=[CH:33][CH:34]=3)=[CH:25][CH:24]=2)[C:20](=[O:37])[N:19]([CH2:38][C:39]([CH3:42])([CH3:41])[CH3:40])[N:18]=1)[CH2:14][CH2:15][CH3:16]>C(OCC)(=O)C>[CH2:13]([C:17]1[N:21]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[C:35]3[NH:3][C:4](=[O:7])[O:5][N:36]=3)=[CH:25][CH:24]=2)[C:20](=[O:37])[N:19]([CH2:38][C:39]([CH3:41])([CH3:40])[CH3:42])[N:18]=1)[CH2:14][CH2:15][CH3:16]
Reactant: CCCCc1nn(CC(C)(C)C)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: O=C([O-])O
Reactant: [NH3+]O
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CCCCc1nn(CC(C)(C)C)c(=O)n1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 66.9 %

Procedure:
A mixture of hydroxylammonium chloride (1.24 g), sodium hydrogen carbonate (1.88 g) and dimethyl sulfoxide (15 mL) was stirred at 40° C. for 30 min, 4′-{[3-butyl-1-(2,2-dimethylpropyl)-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl]methyl}biphenyl-2-carbonitrile (0.6 g) was added, and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (20 mL), N,N′-carbonyldiimidazole (0.29 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.25 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogen sulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.46 g, 72%).
Reaction SMILES: O1CCCC1.[NH2:6][C:7]1[C:15]([NH:16][C:17]2[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=2)[C:20]#[N:21])=[CH:14][CH:13]=[C:12]2[C:8]=1[CH2:9][CH2:10][CH2:11]2.[C:25](Cl)(=[O:30])[CH2:26][C:27](Cl)=[O:28]>CO>[C:20]([C:19]1[CH:18]=[C:17]([N:16]2[C:27](=[O:28])[CH2:26][C:25](=[O:30])[NH:6][C:7]3[C:8]4[CH2:9][CH2:10][CH2:11][C:12]=4[CH:13]=[CH:14][C:15]2=3)[CH:24]=[CH:23][CH:22]=1)#[N:21]
Reactant: O=C(Cl)CC(=O)Cl
Reactant: N#Cc1cccc(Nc2ccc3c(c2N)CCC3)c1
Solvent: CO
Solvent: C1CCOC1
Product: N#Cc1cccc(N2C(=O)CC(=O)Nc3c2ccc2c3CCC2)c1
Reaction time: 1 h
Yield: 29.4 %

Procedure:
To a dry tetrahydrofuran (75 mL) solution of 3-(4-aminoindan-5-ylamino)benzonitrile (0.75 g, 3.00 mmol) was added malonyl chloride (0.35 mL, 3.60 mmol) while stirring in ice-bath. The mixture was stirred under cooling in ice-bath for 1 hour and at room temperature for 1 hour. To the mixture was added methanol (5 mL) while stirring in ice-bath. The mixture was stirred under cooling in ice-bath for 1 hour and at room temperature for 1 hour. To the reaction mixture was added methanol (25 mL) while stirring in ice-bath. The mixture was stirred under cooling in ice-bath for 1 hour and at room temperature for 1 hour. The solvent was removed by evaporation under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/1-4/1) to slightly yellow crystal (0.40 g). The crystal was recrystallized from ethyl acetate to give the titled compound as white crystal (0.28 g, yield 29%).
Reaction SMILES: Cl.[CH3:2][NH2:3].[Cl:4][C:5]1[N:6]=[C:7]([C:12]([NH:14][C@H:15]2[CH2:20][CH2:19][N:18]([C:21]3[S:22][C:23]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:24]([CH:26]=O)[N:25]=3)[CH2:17][C@H:16]2[O:33][CH2:34][CH3:35])=[O:13])[NH:8][C:9]=1[CH2:10][CH3:11].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.ClC(Cl)C.C(OCC)(=O)C>[Cl:4][C:5]1[N:6]=[C:7]([C:12]([NH:14][C@H:15]2[CH2:20][CH2:19][N:18]([C:21]3[S:22][C:23]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:24]([CH2:26][NH:3][CH3:2])[N:25]=3)[CH2:17][C@H:16]2[O:33][CH2:34][CH3:35])=[O:13])[NH:8][C:9]=1[CH2:10][CH3:11]
Reactant: CCOC(=O)c1sc(N2CC[C@H](NC(=O)c3nc(Cl)c(CC)[nH]3)[C@H](OCC)C2)nc1C=O
Reactant: CN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CC(Cl)Cl
Solvent: CO
Solvent: CCOC(C)=O
Product: CCOC(=O)c1sc(N2CC[C@H](NC(=O)c3nc(Cl)c(CC)[nH]3)[C@H](OCC)C2)nc1CNC
Temperature: 25 °C
Reaction time: 2 h
Yield: 28.2 %

Procedure:
3 Å molecular sieves (500 mg) and methylamine hydrochloride (105 mg, 1.55 mmol) were added to a solution of ethyl cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylate obtained in Example (28a) (500 mg, 1.03 mmol) in methanol (5 mL), and the mixture was stirred at room temperature for two hours. The reaction solution was filtered, and then the filtrate was concentrated under reduced pressure. Sodium triacetoxyborohydride (437 mg, 2.06 mmol) was added to a solution of the resulting residue in dichloroethane (10 mL), and the mixture was stirred at room temperature for 20.5 hours. The reaction solution was diluted with ethyl acetate, and then the mixture was extracted with a 1 N aqueous hydrochloric acid solution. A 1 N aqueous sodium hydroxide solution was added to the aqueous layer, followed by extraction with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate. Following filtration, the filtrate was concentrated under reduced pressure to obtain 145 mg of the title compound as a yellow oily substance (28%).
Reaction SMILES: [Si:1]([O:8][C@@H:9]([C@@H:11]1[C@H:14]([C:15]#[C:16][S:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[NH:13][C:12]1=[O:24])[CH3:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].FC(F)(F)C(O)=[O:28].C(=O)(O)[O-].[Na+].[Cl-].[Na+]>C(Cl)Cl.C(OCC)(=O)C.O>[Si:1]([O:8][C@@H:9]([C@@H:11]1[C@@H:14]([CH2:15][C:16]([S:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:28])[NH:13][C:12]1=[O:24])[CH3:10])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]
Reactant: O=C(O)C(F)(F)F
Reactant: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N[C@H]1C#CSc1ccccc1
Agent: O=C([O-])O
Agent: [Cl-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: O
Product: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N[C@@H]1CC(=O)Sc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 89.9 %

Procedure:
To a solution of 3.28 g of (3S, 4R)-3-[(R)-1-t-butyldimethylsilyloxyethyl]-4-[(phenylthio)ethynyl]-2-azetidinone in 75.0 ml of anhydrous methylene chloride were added, under an atmosphere of nitrogen gas, 3.5 ml of trifluoroacetic acid, with stirring and ice-cooling. The mixture was then stirred for 30 minutes under ice-cooling and for a further 1.5 hours at room temperature. The reaction mixture was then poured into a mixture of 1.14 g of sodium bicarbonate, 75 ml of water and 300 ml of ethyl acetate. The mixture was saturated with sodium chloride and the organic layer was separated. The aqueous layer was extracted twice with ethyl acetate. The organic layer and the ethyl acetate extracts were combined, and the combined solution was washed successively with an aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulphate. The solvent was distilled off under reduced pressure and the residue was subjected to column chromatography through silica gel, eluted with a 3:1 by volume mixture of cyclohexane and ethyl acetate, to give 3.09 g (yield 89.9%) of the title thioester compound, melting at 94°-95° C.
Reaction SMILES: CC[CH2:3][CH2:4][CH2:5][CH3:6].C([Li])CCC.[C:12]1(=[O:18])[CH2:17][CH2:16][CH2:15][CH:14]=[CH:13]1.[C:19](Cl)(=[O:21])[CH3:20]>CCOCC.CN(C)P(=O)(N(C)C)N(C)C>[C:19]([CH:13]1[CH:14]([CH2:6][CH2:5][CH2:4][CH3:3])[CH2:15][CH2:16][CH2:17][C:12]1=[O:18])(=[O:21])[CH3:20]
Reactant: CCCCCC
Reactant: O=C1C=CCCC1
Reactant: CC(=O)Cl
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: CCCCC1CCCC(=O)C1C(C)=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 92 %

Procedure:
In the same way as in Example 4, 15.3 ml (20 mmol) of a 1.31 M hexane solution of n-butyllithium was reacged with a solution of 960 mg (10 mmol) of 2-cyclohexenone in 5 ml of ether at -78° C. for 30 minutes in the presence of 3.90 g (10 mmol) of tri-n-butylphosphine-copper (I) iodide complex. Then, a mixture consisting of 4 ml (56 mmol) of acetyl chloride, 5 ml of hexamethylphosphoric triamide and 10 ml of ether was rapidly added, and the mixture was stirred for 4 hours while gradually raising the temperature to room temperature. After the reaction, the reaction product was post-treated, extracted, washed, and dried in the same way as in Example 4 to afford 5.48 g of a crude product. The crude product was purified by distillation at reduced pressure to afford 1.81 g of 2-acetyl-3-n-butylcyclohexanone (boiling point 64°-66° C./0.06 mmHg, 92%).
Reaction SMILES: [O:1]([CH:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])/[CH:10]=[CH:11]/I)[Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3].C([Li:22])CCC>CCCCCC>[O:1]([CH:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])/[CH:10]=[CH:11]/[Li:22])[Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3]
Reactant: CCCCCC(/C=C/I)O[Si](C)(C)C(C)(C)C
Reactant: [Li]CCCC
Solvent: CCCCCC
Product: [Li]/C=C/C(CCCCC)O[Si](C)(C)C(C)(C)C
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
On the other hand, 736 mg (2 mmol) of 3-t-butyldimethylsiloxy-1-iodo-trans-1-octene was added to 2 ml. of anhydrous hexane, and 1.4 ml. (2 mmol) of a 1.4 M hexane solution of n-butyllithium was added. The mixture was stirred at -78° C for 30 minutes in an atmosphere of nitrogen to afford an anhydrous hexane solution of 3-t-butyldimethylsiloxy-1-lithio-trans-1-octene. The resulting solution was added dropwise to the anhydrous diethyl ether solution of copper pentylide obtained previously, and the mixture was stirred at -78° C for 30 minutes to afford a solution of an organic copper lithium compound of the following formula ##STR19##
Reaction SMILES: [N+](=[CH:3][C:4]([C:6]1[O:7][CH:8]=[CH:9][CH:10]=1)=[O:5])=[N-].[Cl:11][C:12]1[C:13](=[O:22])[C:14](=[O:21])[C:15]([Cl:20])=[C:16]([Cl:19])[C:17]=1[Cl:18]>C1C=CC=CC=1>[O:7]1[CH:8]=[CH:9][CH:10]=[C:6]1[C:4]([CH:3]1[O:22][C:13]2[C:12]([Cl:11])=[C:17]([Cl:18])[C:16]([Cl:19])=[C:15]([Cl:20])[C:14]=2[O:21]1)=[O:5]
Reactant: [N-]=[N+]=CC(=O)c1ccco1
Reactant: O=C1C(=O)C(Cl)=C(Cl)C(Cl)=C1Cl
Solvent: c1ccccc1
Product: O=C(c1ccco1)C1Oc2c(Cl)c(Cl)c(Cl)c(Cl)c2O1
Yield: 8.5 %

Procedure:
2-diazo-1-(furan-2-yl)ethanone (900 mg, 6.61 mmol) and 3,4,5,6-tetrachlorocyclohexa-3,5-diene-1,2-dione (846 mg, 10.05 mmol) were combined in dry benzene (10 ml) and refluxed vigorously for 6 hours. The solvent was evaporated to dryness, and the resulting crude material was subjected to column chromatography using 100-200 mesh range silica gel and an ethyl acetate/hexane solvent system. The crude material was a mixture of two compounds, which were separated by column chromatography. Crystallization from acetone yielded furan-2-yl(4,5,6,7-tetrachlorobenzo[d][1,3]dioxol-2-yl)methanone as a yellow solid (200 mg, 16.4%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[C@@:12]([CH3:27])([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=3)[NH:11][C:10]2=S)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:29][O:30][CH:31]([O:34][CH3:35])[CH2:32][NH2:33].C(OO)(C)(C)C.OS([O-])=O.[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[C@@:12]([CH3:27])([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=3)[NH:11]/[C:10]/2=[N:33]\[CH2:32][CH:31]([O:34][CH3:35])[O:30][CH3:29])[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: C[C@]1(Cc2ccc(OC(F)(F)F)cc2)NC(=S)N(c2cc(Cl)cc(Cl)c2)C1=O
Reactant: COC(CN)OC
Agent: CC(C)(C)OO
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CO
Product: COC(C/N=C1\N[C@](C)(Cc2ccc(OC(F)(F)F)cc2)C(=O)N1c1cc(Cl)cc(Cl)c1)OC
Temperature: 25 °C
Reaction time: 0.42 h
Yield: 100.6 %

Procedure:
To a solution of the above thiohydantoin (4.47 g, 9.95 mmol) and aminoacetaldehyde dimethylacetal (6.50 mL, 59.7 mmol) in 20 mL of MeOH was added 7.69 mL (59.7 mmol, 70% in water) of t-butyl hydroperoxide solution, dropwise over 25 min. During the addition and for about 1 h after, the internal temperature of the mixture was kept below 20° C. with an ice water bath. The mixture was stirred at room temperature for 86 h, and 25 mL of saturated NaHSO3 solution was added slowly dropwise, maintaining the internal temperature below 20° C. with an ice water bath. The resulting cloudy white mixture was concentrated. To the residue was added EtOAc, and this mixture was concentrated again. The oily residue was partitioned between EtOAc and water, and the aqueous phase was separated and extracted with EtOAc. The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated to give 5.21 g of (R)-3-(3,5-dichloro-phenyl)-2-[(E)-2,2-dimethoxy-ethylimino]-5-methyl-5-(4-trifluoromethoxy-benzyl)-imidazolidin-4-one as a thick yellow oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10](=[O:12])[CH3:11])=[C:5]([CH3:13])[CH:4]=1.[Se](=O)=[O:15]>O1CCOCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:15])[C:10](=[O:12])[CH3:11])=[C:5]([CH3:13])[CH:4]=1
Reactant: O=[Se]=O
Reactant: COc1ccc(CC(C)=O)c(C)c1
Solvent: C1COCCO1
Product: COc1ccc(C(=O)C(C)=O)c(C)c1
Temperature: 100 °C

Procedure:
C8 (6.00 g, 33.7 mmol) and selenium dioxide (7.47 g, 67.3 mmol) were suspended in 1,4-dioxane (50 mL) and heated at 100° C. for 18 hours. The reaction mixture was cooled to room temperature and filtered through Celite; the filtrate was concentrated in vacuo. Silica gel chromatography (Eluent: 10% ethyl acetate in heptane) afforded the product as a bright yellow oil. Yield: 2.55 g, 13.3 mmol, 39%. LCMS m/z 193.1 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J=8.6 Hz, 1H), 6.81 (br d, half of AB quartet, J=2.5 Hz, 1H), 6.78 (br dd, half of ABX pattern, J=8.7, 2.6 Hz, 1H), 3.87 (s, 3H), 2.60 (br s, 3H), 2.51 (s, 3H).