Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Li])CCC.[CH2:6]([OH:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH2:14]([C@@H:21]([CH2:33][CH:34]=[CH2:35])[C:22](N1[C@@H](C(C)C)COC1=O)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[Cl-].[NH4+]>O1CCCC1.CCCCCC>[CH2:14]([C@H:21]([CH2:33][CH:34]=[CH2:35])[C:22]([O:13][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: C=CC[C@H](Cc1ccccc1)C(=O)N1C(=O)OC[C@@H]1C(C)C
Reactant: OCc1ccccc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: C=CC[C@@H](Cc1ccccc1)C(=O)OCc1ccccc1
Reaction time: 0.17 h
Yield: 93.8 %

Procedure:
5.63 ml (9.01 mmoles) of butyllithium (as a 1.6M hexane solution) were added, whilst ice-cooling and under an atmosphere of nitrogen, to a solution of 1.24 ml (12.0 mmoles) of benzyl alcohol in 20 ml of anhydrous tetrahydrofuran. The mixture was stirred for 10 minutes, and then a solution of 1.81 g (6.01 mmoles) of 3-[2(R)-benzyl-4-pentenoyl]-4(S)-isopropyl-2-oxazolidinone (prepared by a procedure similar to that described in Preparation 17) in 10 ml of anhydrous tetrahydrofuran was added dropwise thereto. The mixture was then stirred for 30 minutes, after which a saturated aqueous solution of ammonium chloride was added to the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, the solvent was removed by distillation under reduced pressure, and the residue was purified by medium pressure silica gel column chromatography (using a 10:1 by volume mixture of hexane and ethyl acetate as eluent), to give 1.58 g (yield 94%) of the title compound as a colorless oily substance.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[C:7]([NH:12][C:13]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)=[O:14])[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.Cl.C1C[O:31]CC1>C(OCC)(=O)C>[OH:31][C:2]1[C:11]2[C:6](=[C:7]([NH:12][C:13]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)=[O:14])[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1
Reactant: C1CCOC1
Reactant: O=C(NCc1ccc(C(F)(F)F)cc1)Nc1cccc2c(Cl)nccc12
Agent: Cl
Solvent: CCOC(C)=O
Product: O=C(NCc1ccc(C(F)(F)F)cc1)Nc1cccc2c(O)nccc12
Temperature: 90 °C

Procedure:
N-(1-chloroisoquinolin-5-yl)-N′-[4-(trifluoromethyl)benzyl]urea (Example 69; 47 mg, 0.12 mmol) was added to a mixture of 3N HCl (aq. 5 ml) and THF (1 ml). The mixture was heated at 90° C. for 20 hours, then 5N HCl (aq. 2 ml) was added and the reaction heated at 90° C. for a further 20 hours. After cooling to room temperature, ethyl acetate (20 ml) was added and the layers separated (some solid was suspended in the organic layer). The organic phase was washed with saturated aqueous NaHCO3 (20 ml), then evaporated. The residue was triturated in refluxing isopropyl alcohol (5 ml), then cooled to room temperature. The white solid was collected by filtration and washed with isopropyl alcohol (2×1 ml) to give the title compound (22 mg). m/z (ES+) 362 (M+H)+.
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[Cl:12][C:13]1[CH:22]=[C:21]([C:23]#[C:24][CH2:25][N:26]([CH3:28])[CH3:27])[CH:20]=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16]>ClCCl>[Cl:12][C:13]1[CH:22]=[C:21]([C:23](=[O:6])[CH:24]=[CH:25][N:26]([CH3:28])[CH3:27])[CH:20]=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COC(=O)c1ccc(C#CCN(C)C)cc1Cl
Solvent: ClCCl
Product: COC(=O)c1ccc(C(=O)C=CN(C)C)cc1Cl
Temperature: -20 °C
Reaction time: 0.21 h

Procedure:
Gradually, 3-chloroperoxybenzoic acid (10.76 g) was added to a solution of 2-chloro-4-(3-dimethylamino-propyn-1yl)-benzoic acid, methyl ester (15.07 g in dichloromethane (40 ml), at a rate to maintain the reaction temperature at −20° C. The mixture was stirred for 10-15 minutes. The resulting N-oxide was purified by chromatography on Activity Grade I basic alumina (215 g), eluting with 10% methanol/dichloromethane. The solvent was evaporated in vacuo between 12 to 18° C. The resulting residue was dissolved in methanol (100 ml) and heated at 60-65° C. with stirring for 18 hours. After removing the solvent in vacuo, and the product was purified by column chromatography on silica gel (190 g), eluting with 70% ethyl acetate/hexane. Trituration with diethyl ether containing some hexane afforded the title compound as a solid (5.68 g), m.p. 92-96° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:11][C:10](=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:13][O:14][C:15]([CH:17]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:16]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10](=[CH:17][C:15]([O:14][CH3:13])=[O:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)OC(=O)N1CC(=O)C1
Solvent: Cc1ccccc1
Product: COC(=O)C=C1CN(C(=O)OC(C)(C)C)C1

Procedure:
3-Oxo-azetidine-1-carboxylic acid tert-butyl ester (1.67 g; 9.7 mmol) and methoxycarbonyl-methylene-triphenylphosphorane (3.42 g; 10.25 mmol) are dissolved in toluene (5 ml), refluxed for 2.5 hours and left over night at room temperature. The precipitate is filtered off, washed with TBME, and the filtrate purified via chromatography (TBME/hexane 2:8>3:7) to yield the title compound as colorless crystals. 1H-NMR (400 MHz; DMSO-d6): 5.90 (m, 1H); 4.71 (bs, 2H); 4.58 (bs, 2H); 3.67 (s, 3H); 1.42 (s, 9H). MS (m/z) ES+: 171 (10; MH+ minus tert-butyl); 57 (100).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][N:5]1[C:9](=[O:10])[CH2:8][S:7][C:6]1=[O:11].[CH3:12][C:13]1[CH:14]=[C:15]([N:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH:16]=[CH:17][CH:18]=1>>[CH3:12][C:13]1[CH:14]=[C:15]([N:19]2[CH2:24][CH2:23][N:22]([CH2:2][CH2:3][CH2:4][N:5]3[C:9](=[O:10])[CH2:8][S:7][C:6]3=[O:11])[CH2:21][CH2:20]2)[CH:16]=[CH:17][CH:18]=1
Reactant: Cc1cccc(N2CCNCC2)c1
Reactant: O=C1CSC(=O)N1CCCBr
Product: Cc1cccc(N2CCN(CCCN3C(=O)CSC3=O)CC2)c1

Procedure:
Reaction of 3-(3-bromopropyl)-2,4-thiazolidinedione with 1-(3-methylphenyl)piperazine according to the procedure of Example I(c) affords 3-[3-[4-(3-METHYLPHENYL)-1-PIPERAZINYL]PROPYL]-2,4-THIAZOLIDINEDIONE.
Reaction SMILES: [CH3:1][C:2]([C@H:4]1[C@@H:8]2[C@H:9]3[C@@:14]([CH3:17])([CH2:15][CH2:16][C@@:7]2([CH:31]=[O:32])[CH2:6][CH2:5]1)[C@:13]1([CH3:30])[CH2:18][CH2:19][C@H:20]2[C:26]([CH3:28])([CH3:27])[C:24](=[O:25])[CH:23]=[CH:22][C@:21]2([CH3:29])[C@H:12]1[CH2:11][CH2:10]3)=[CH2:3].OO.[O-:35]Cl=O.[Na+]>CC#N.O.O>[CH3:3][C:2]([C@H:4]1[C@@H:8]2[C@@H:9]3[C@@:14]([CH3:17])([CH2:15][CH2:16][C@@:7]2([C:31]([OH:35])=[O:32])[CH2:6][CH2:5]1)[C@@:13]1([CH3:30])[C@@H:12]([C@:21]2([CH3:29])[C@@H:20]([CH2:19][CH2:18]1)[C:26]([CH3:28])([CH3:27])[C:24](=[O:25])[CH2:23][CH2:22]2)[CH2:11][CH2:10]3)=[CH2:1]
Reactant: C=C(C)[C@@H]1CC[C@]2(C=O)CC[C@]3(C)[C@@H](CC[C@@H]4[C@@]5(C)C=CC(=O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Reactant: [O-][Cl+][O-]
Agent: OO
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: C=C(C)[C@@H]1CC[C@]2(C(=O)O)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CCC(=O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Temperature: 2.5 °C
Reaction time: 1 h

Procedure:
The betulone aldehyde prepared from the last step is dissolved in a mixture of NaH2PO4.H2O (877 mg) and CH3CN—H2O (17 mL) and the suspension cooled to 0-5° C. 30% aqueous H2O2 (220 μL) and a solution of NaClO2 (200 mg) in water (16 mL) are then successively added, the mixture warmed to room temperature and stirred at this temperature for 1 h. The reaction is quenched by addition of Na2S2O5 (380 mg), and extracted with ethyl acetate. The organic extract is washed with water and brine, dried (Na2SO4), filtered, and concentrated. The residue is then subjected to column chromatography to afford betulonic acid (550 mg) as white solid.
Reaction SMILES: Br[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]3=[C:7]([CH3:16])[C:6]=2[CH:5]=[C:4]([F:17])[CH:3]=1.[O:18]1[C:22]2[CH:23]=[CH:24][C:25](B(O)O)=[CH:26][C:21]=2[CH2:20][CH2:19]1>>[O:18]1[C:22]2[CH:23]=[CH:24][C:25]([C:2]3[C:10]4[N:9]5[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]5=[C:7]([CH3:16])[C:6]=4[CH:5]=[C:4]([F:17])[CH:3]=3)=[CH:26][C:21]=2[CH2:20][CH2:19]1
Reactant: Cc1c2n(c3c(Br)cc(F)cc13)CCNC2=O
Reactant: OB(O)c1ccc2c(c1)CCO2
Product: Cc1c2n(c3c(-c4ccc5c(c4)CCO5)cc(F)cc13)CCNC2=O

Procedure:
The title compound, white solid (70 mg, 83%), MS (ISP) m/z=337.5 [(M+H)+], mp 251° C., was prepared in accordance with the general method of example 1 from 6-bromo-8-fluoro-10-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (intermediate 14) (74.3 mg, 0.25 mmol) and commercially available 2,3-dihydro-benzofuran-5-ylboronic acid (53.3 mg, 0.325 mmol).
Reaction SMILES: [ClH:1].[Cl:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][NH:10][CH2:11][CH2:12][C:13]1[S:14][CH:15]=[CH:16][CH:17]=1.O1CCCO[CH2:19]1.Cl>C(O)(C)C>[CH:6]1[CH:7]=[CH:8][C:3]([Cl:2])=[C:4]([CH2:9][N:10]2[CH2:19][C:17]3[CH:16]=[CH:15][S:14][C:13]=3[CH2:12][CH2:11]2)[CH:5]=1.[ClH:1]
Reactant: Clc1ccccc1CNCCc1cccs1
Reactant: C1COCOC1
Agent: Cl
Solvent: CC(C)O
Product: Clc1ccccc1CN1CCc2sccc2C1
Temperature: 80 °C
Yield: 82 %

Procedure:
N-[(2-chlorophenyl-methyl)]-2-(2-thienyl)ethylamine HCl (28.8 g) is suspended in 75 ml of iso-propanol. 1,3-Dioxane (13.2 g) and 0.25 ml of hydrochloric acid (37% concentration) are added. The reaction mixture is heated to 80° C. for 24 hours. Thereafter, the mixture is cooled to 10° C. and the precipitate is filtered and washed twice with 10 ml of frozen iso-propanol. The product is desiccated at 60° C. UV to yield 24.6 g (82%) Ticlopidine hydrochloride with chemical-physical characteristics as described in Example 1.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8](=[O:19])[CH2:9][O:10][C:11]2[C:12](=[O:18])[N:13]([CH3:17])[N:14]=[CH:15][CH:16]=2)[CH2:4][CH2:3]1.[F:20][C:21]([F:31])([F:30])[O:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1O>>[CH3:17][N:13]1[C:12](=[O:18])[C:11]([O:10][CH2:9][C:8](=[O:19])[N:5]2[CH2:4][CH2:3][CH:2]([O:1][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[O:22][C:21]([F:20])([F:31])[F:30])[CH2:7][CH2:6]2)=[CH:16][CH:15]=[N:14]1
Reactant: Oc1ccccc1OC(F)(F)F
Reactant: Cn1nccc(OCC(=O)N2CCC(O)CC2)c1=O
Product: Cn1nccc(OCC(=O)N2CCC(Oc3ccccc3OC(F)(F)F)CC2)c1=O
Yield: 20 %

Procedure:
Compound 21 is prepared from intermediate 5c and 2-trifluoromethoxy-phenol following synthesis method 3 (yield: 20%).
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[O:14][C:13]([C:15]#[N:16])=[CH:12][CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[NH2:17][OH:18]>>[Si:1]([O:8][CH2:9][C:10]1[O:14][C:13]([C:15](=[N:17][OH:18])[NH2:16])=[CH:12][CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OCc1ccc(C#N)o1
Reactant: NO
Product: CC(C)(C)[Si](C)(C)OCc1ccc(C(N)=NO)o1

Procedure:
The crude product of the title compound was synthesized by conducting the similar reaction to that mentioned in Example 1 (1d) using 5-({[t-butyl(dimethyl)silyl]oxy}methyl)-2-furonitrile (7.5 g, 32 mmol) that was obtained in Example 2 (2a) and a 40% aqueous solution of hydroxylamine (4.0 ml). Subsequently, the crude product of the title compound thus obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and hexane (1:1) as the eluent to afford the title compound (8.1 g) in a yield of 95% as a white crystalline solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]([CH:13]([OH:15])[CH3:14])=[CH:11][N:12]=2)=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:9][C:10]([C:13](=[O:15])[CH3:14])=[CH:11][N:12]=2)=[CH:6][CH:7]=1
Reactant: CC(O)c1cnc(-c2ccc(F)cc2)s1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: CC(=O)c1cnc(-c2ccc(F)cc2)s1
Temperature: 25 °C
Reaction time: 2 h
Yield: 84.2 %

Procedure:
A solution of 1-(2-(4-fluorophenyl)thiazol-5-yl)ethanol (1.0 g, 4.4 mmol) in dichloromethane (40 mL) was cooled to 0° C. Dess-Martin periodinane (5.7 g, 13.4 mmol) was added slowly at 0° C. and the reaction mixture stirred at room temperature for 2 h. The reaction mixture was quenched with saturated NaHCO3 solution (80 mL), sodium thiosulfate solution (20 mL), extracted with ether (2×1000 mL), the organic layer dried over Na2SO4, filtered and concentrated to obtain crude product. The crude product was purified by Combiflash® chromatography (40% ethyl acetate in hexane) to afford 1-(2-(4-fluorophenyl)thiazol-5-yl)ethanone as off-white solid (820 mg, 83% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.67 (s, 1H), 8.08 (t, 2H), 7.37 (t, 2H), 2.59 (s, 3H); LC-MS m/z calculated for [M+H]+222.03. found 222.3.
Reaction SMILES: [CH3:1][C@@:2]1([C:18]([F:21])([F:20])[F:19])[CH2:17][N:5]2[C:6](=[O:16])[CH:7]=[C:8]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[N:9]=[C:4]2[NH:3]1.Br[CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>>[Cl:31][C:27]1[CH:26]=[C:25]([CH2:24][CH2:23][N:3]2[C:4]3=[N:9][C:8]([N:10]4[CH2:11][CH2:12][O:13][CH2:14][CH2:15]4)=[CH:7][C:6](=[O:16])[N:5]3[CH2:17][C@@:2]2([CH3:1])[C:18]([F:21])([F:19])[F:20])[CH:30]=[CH:29][CH:28]=1
Reactant: Clc1cccc(CCBr)c1
Reactant: C[C@@]1(C(F)(F)F)Cn2c(nc(N3CCOCC3)cc2=O)N1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: C[C@@]1(C(F)(F)F)Cn2c(nc(N3CCOCC3)cc2=O)N1CCc1cccc(Cl)c1

Procedure:
The product is prepared according to the procedure described in stage k of Example 1, using 100 mg of (2S)-2-methyl-7-(morpholin-4-yl)-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one (Example 1j) and 87 mg of 1-(2-bromoethyl)-3-chlorobenzene, replacing the sodium hydride with 214 mg of caesium carbonate. After purification by preparative HPLC/MS (method C), 38 mg of (2S)-1-[2-(3-chlorophenyl)ethyl]-2-methyl-7-(morpholin-4-yl)-2-(trifluoromethyl)-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)one are obtained in the form of an oil, the characteristics of which are the following:
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([N+:9]([O-])=O)=[CH:4][N:3]=1.O>C(O)(=O)C.[Fe]>[NH2:9][C:5]1[CH:4]=[N:3][C:2]([Cl:1])=[C:7]([Cl:8])[CH:6]=1
Reactant: O=[N+]([O-])c1cnc(Cl)c(Cl)c1
Agent: [Fe]
Solvent: CC(=O)O
Solvent: O
Product: Nc1cnc(Cl)c(Cl)c1

Procedure:
77.2 g (0.4 mol) of 2,3-dichloro-5-nitropyridine were dissolved in 135 ml of glacial acetic acid, and 800 ml of water were added with stirring. 111.7 g (2 mol) of iron powder were introduced in portions into the mixture (temperature≤50° C.). After completion of the reaction, the mixture is filtered under suction and the product extracted using ethyl acetate. The organic phase was washed with water until neutral, dried using MgSO4 and concentrated by evaporation. The product was recrystallized from toluene.
Reaction SMILES: Cl[C:2]1[N:17]=[C:5]2[C:6]([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([C:31]2[CH:36]=[CH:35][C:34]([NH2:37])=[CH:33][CH:32]=2)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]>>[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([C:31]2[CH:36]=[CH:35][C:34]([NH:37][C:2]3[N:17]=[C:5]4[C:6]([C:10]5[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=5)=[CH:7][CH:8]=[CH:9][N:4]4[N:3]=3)=[CH:33][CH:32]=2)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:19])[CH3:20]
Reactant: Fc1ccc(-c2cccn3nc(Cl)nc23)cc1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(N)cc2)CC1
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(Nc3nc4c(-c5ccc(F)cc5)cccn4n3)cc2)CC1

Procedure:
4-{4-[8-(4-Fluoro-phenyl)-[1,2,4]-triazolo[1,5-a]pyridin-2-ylamino]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester was prepared from 2-chloro-8-(4-fluoro-phenyl)-[1,2,4]-triazolo[1,5-a]pyridine (0.190 g, 0.767 mmol) and 4-(4-amino-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (0.254 g, 0.921 mmol) in a manner analogous to Example 311a and 311b to give product. MP=88-91° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.65 (s, 1H), 8.79 (d, 1H), 8.22 (m, 2H), 7.82 (d, 1H), 7.60 (d, 2H), 7.35 (m, 2H), 7.15 (d, 2H), 7.10 (m, 1H), 4.05 (m, 2H), 2.80 (m, 2H), 2.60 (m, 1H), 1.75 (m, 2H), 1.45 (m, 2H), 1.41 (s, 9H): MS=488 (MH)+.
Reaction SMILES: [CH3:1][CH:2]([CH3:5])[CH:3]=[CH2:4].CCCCCCCCCC.[O:16]=O>[Br-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.[Ti].[Pd](Cl)Cl.O>[CH3:1][CH:2]([CH3:5])[CH:3]=[CH2:4].[CH:2]([C:3]([CH3:4])=[O:16])([CH3:5])[CH3:1]
Reactant: O=O
Agent: Cl[Pd]Cl
Agent: [Ti]
Agent: C=CC(C)C
Solvent: CCCCCCCCCC
Solvent: O
Product: CC(=O)C(C)C
Reaction time: 2 h

Procedure:
The oxidation of 3-methyl-1-butene was carried out in a 300 cc titanium Autoclave Engineers magnedrive stirred tank reactor. The reactor was charged with 50 mL water, 50 g (68 mL) decane, 0.01 mol palladium chloride, 0.025 mol heteropolyacid, 0.004 mol cetyltrimethylammonium bromide, and 0.29 mol 3-methyl-1-butene. Reaction was carried out for 2 hours, at 120° C. and 150 psig oxygen pressure according to the general procedure set forth above. A 22.1 mol % conversion of 3-methyl-1-butene was obtained with 37.1% selectivity to methyl isopropyl ketone.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH3:20])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:21](OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:22][CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:39]([C:42]1[CH:47]=[CH:46][C:45](B(O)O)=[CH:44][CH:43]=1)(=[O:41])[CH3:40].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH3:20])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:21]([C:45]2[CH:46]=[CH:47][C:42]([C:39](=[O:41])[CH3:40])=[CH:43][CH:44]=2)=[CH:22][CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)(=[O:8])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(=O)c1ccc(B(O)O)cc1
Reactant: COc1cnc2c(c1)cc(C(=CC1CCCC1)OS(=O)(=O)c1ccc(C)cc1)n2S(=O)(=O)c1ccccc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: COc1cnc2c(c1)cc(C(=CC1CCCC1)c1ccc(C(C)=O)cc1)n2S(=O)(=O)c1ccccc1
Yield: 93.8 %

Procedure:
To a mixture of toluene-4-sulfonic acid-1-(benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-vinyl ester (prepared as in Example 12, 1 g, 1.81 mmol), 4-acetylphenylboronic acid (743 mg, 4.53 mmol), and dichlorobis(triphenylphosphine)palladium (II) (127 mg, 0.18 mmol) in dioxane (5 mL) was added an aqueous sodium carbonate solution (2 M, 2.3 mL, 4.6 mmol). The resulting mixture was subjected to microwave irradiation for 2 h at 100° C. The mixture was diluted with ethyl acetate (250 mL), washed with a saturated aqueous sodium bicarbonate solution (2×50 mL), brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 20% ethyl acetate/hexanes) afforded 1-{4-[1-(1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-vinyl]-phenyl}-ethanone (850 mg, 93.9%) as a light yellow solid: LC/MS m/e calcd for C29H28N2O4S [M+H]+ 501.62, observed 501.2.
Reaction SMILES: [CH2:1]1[CH:5]2[CH:6]3C=CC([CH:4]2[CH:3]=[CH:2]1)C3.C[SiH:12]([Cl:14])[Cl:13].CCCCCCCCCCCCCCCC>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1>[CH:5]1([CH2:6][SiH:12]([Cl:14])[Cl:13])[CH2:4][CH2:3][CH:2]=[CH:1]1
Reactant: C1=CC2C3C=CC(C3)C2C1
Reactant: C[SiH](Cl)Cl
Agent: Cl[Pd]Cl
Agent: c1ccc(P(CCCCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Solvent: CCCCCCCCCCCCCCCC
Solvent: Cc1ccccc1
Product: Cl[SiH](Cl)CC1C=CCC1
Reaction time: 2 h
Yield: 337.4 %

Procedure:
As described in Example 2, 2.85 g (0.0216 mol) of dicyclopentadiene, 3.72 g (0.0323 mol) of methyldichlorosilane, 0.040 g (0.000226 mol) of palladium dichloride, 0.19 g (0.000451 mol) of 1,4-bis(diphenylphosphino)butane and 4 mL of toluene and 2 mL of hexadecane were placed in a reactor. The reactor was sealed and the reaction was performed at 180° C. for 2 hours. Products were subject to simple vacuum distillation, thereby providing a mixture (13.2 g) of (2-cyclopentenyl)methyldichlorosilane (4.1 g, 70%), other unreacted reactants, toluene, hexadecane, and unidentified compounds.
Reaction SMILES: [C:1]([CH2:4][N:5]1[C:9]([S:10][C:11]2[CH:16]=[C:15]([Cl:17])[CH:14]=[C:13]([Cl:18])[CH:12]=2)=[C:8]([CH:19]([CH3:21])[CH3:20])[N:7]=[C:6]1[CH2:22][O:23]CC1C=CC(OC)=CC=1)(=[O:3])[CH3:2].N(CC1N(CC)C(C(C)C)=C(SC2C=C(F)C=C(F)C=2)N=1)=[N+]=[N-]>>[C:1]([CH2:4][N:5]1[C:9]([S:10][C:11]2[CH:16]=[C:15]([Cl:17])[CH:14]=[C:13]([Cl:18])[CH:12]=2)=[C:8]([CH:19]([CH3:20])[CH3:21])[N:7]=[C:6]1[CH2:22][OH:23])(=[O:3])[CH3:2]
Reactant: COc1ccc(COCc2nc(C(C)C)c(Sc3cc(Cl)cc(Cl)c3)n2CC(C)=O)cc1
Agent: CCn1c(CN=[N+]=[N-])nc(Sc2cc(F)cc(F)c2)c1C(C)C
Product: CC(=O)Cn1c(CO)nc(C(C)C)c1Sc1cc(Cl)cc(Cl)c1

Procedure:
Compound I-32 was obtained from 1-acetylmethyl-5-(3,5-dichlorophenylthio)-4-isopropyl-2-(p-methoxybenzyloxymethyl)-1H-imidazole (17v) by the same synthetic process as that for Compound I-16 in Example 16 (yield 45%). mp 165-167° C.
Reaction SMILES: [CH:1]([C:4]1[C:13]2[CH:12]=[C:11]([NH:14][C:15]3[CH:25]=[CH:24][C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:17][CH:16]=3)[C:10]([CH3:26])=[CH:9][C:8]=2[C:7]([CH3:28])([CH3:27])[CH2:6][CH:5]=1)(C)[CH3:2].C(=O)C>>[CH2:1]([C:4]1[C:13]2[CH:12]=[C:11]([NH:14][C:15]3[CH:16]=[CH:17][C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:24][CH:25]=3)[C:10]([CH3:26])=[CH:9][C:8]=2[C:7]([CH3:28])([CH3:27])[CH2:6][CH:5]=1)[CH3:2]
Reactant: CCOC(=O)c1ccc(Nc2cc3c(cc2C)C(C)(C)CC=C3C(C)C)cc1
Agent: CC=O
Product: CCOC(=O)c1ccc(Nc2cc3c(cc2C)C(C)(C)CC=C3CC)cc1
Yield: 55.9 %

Procedure:
Following General Procedure D, ethyl 4-[(8-isopropyl-3,5,5-trimethyl-5,6-dihydronaphthalen-2-yl)amino]benzoate (Compound 17, 0.48 g, 1.28 mmol) was reacted with acetaldehyde (0.9 mL, 12.8 mmol) to give 0.26 g (50%) of the title compound as a clear oil.
Reaction SMILES: [OH-].[Na+].[C:3]1([P:9]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:10]2[CH:11]=[C:12]([CH2:16][PH:17](=[O:23])[O:18]CC(C)C)[CH:13]=[CH:14][CH:15]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl>O.C1COCC1>[C:3]1([P:9]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:10]2[CH:11]=[C:12]([CH2:16][PH:17](=[O:18])[OH:23])[CH:13]=[CH:14][CH:15]=2)[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: CC(C)CO[PH](=O)Cc1cccc(P(c2ccccc2)c2ccccc2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=[PH](O)Cc1cccc(P(c2ccccc2)c2ccccc2)c1
Temperature: 23 °C
Reaction time: 0.17 h
Yield: 47.6 %

Procedure:
0.50 g (12.6 mmol) of NaOH in 7 ml of water are added dropwise at 23° C. to a solution of 2.50 g (6.3 mmol) of isobutyl (3-diphenylphosphinophenyl)methylphosphinate in 7 ml of THF. After refluxing for 6 hours, 1.04 ml (12.6 mmol) of concentrated hydrochloric acid are added dropwise at 23° C., the mixture is stirred for 10 min at 23° C. and evaporated to dryness under reduced pressure. The residue is substantially dissolved in boiling methanol, filtered hot and crystallized for 22 h at -20° C. 1.02 g of (3-diphenylphosphinophenyl)methylphosphinic acid (60% of theory) are obtained in the form of a colorless solid having an m.p. of 173° C.