Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]=[C:12]=[O:13])=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[CH3:14][NH:15][C:16]1[CH:17]=[C:18]([C:22]2[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:24][CH:23]=2)[CH:19]=[CH:20][CH:21]=1>>[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:13])[N:15]([C:16]2[CH:17]=[C:18]([C:22]3[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:24][CH:23]=3)[CH:19]=[CH:20][CH:21]=2)[CH3:14])=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCOC(=O)CCc1ccc(-c2cccc(NC)c2)cc1
Reactant: CCCCc1ccc(N=C=O)cc1
Product: CCCCc1ccc(NC(=O)N(C)c2cccc(-c3ccc(CCC(=O)OCC)cc3)c2)cc1
Temperature: 100 °C
Yield: 96.4 %

Procedure:
345 mg (1.5 mmol, 1.5 eq) of 1-butyl-4-isocyanatobenzene are added to 283 mg (1.0 mmol, 1 eq) of ethyl 3-(3′-methylaminobiphenyl-4-yl)propanoate (prepared in Example 7c). The reaction mixture is heated at 100° C. by microwave for 30 minutes. The mixture is chromatographed on silica gel (15 g FlashSmart column) eluted with 80/20 heptane/ethyl acetate. 442 mg of ethyl 3-{3′-[3-(4-butylphenyl)-1-methylureido]biphenyl-4-yl}propanoate are obtained in the form of a yellow oil that crystallizes. Yield=96%
Reaction SMILES: [CH3:1][Si:2]([CH3:11])([CH3:10])[C:3]1[CH:4]=[C:5]([CH3:9])[CH:6]=[CH:7][CH:8]=1.[Br:12]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[CH3:1][Si:2]([CH3:10])([CH3:11])[C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][CH:8]=1)[CH2:9][Br:12]
Reactant: Cc1cccc([Si](C)(C)C)c1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: C[Si](C)(C)c1cccc(CBr)c1

Procedure:
A mixture of 3-trimethylsilyltoluene (3.28 g, 10 mmol), N-bromosuccinimide (1.78 g, 10 mmol) and benzoylperoxide (10 mg) in CCl4 (20 ml) was stirred under reflux for 3 hours, then cooled and filtered. The solvent was removed under reduced pressure and 3-trimethylsilylbenzylbromide was purified by distillation.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:21])[C:5]([CH3:20])([CH3:19])[CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18])[CH3:2].[BrH:22]>C(O)(=O)C>[CH2:1]([O:3][C:4](=[O:21])[C:5]([CH3:20])([CH3:19])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH:11]([Br:22])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18])[CH3:2]
Reactant: Br
Reactant: CCOC(=O)C(C)(C)CCCCC=Cc1ccccc1Cl
Solvent: CC(=O)O
Product: CCOC(=O)C(C)(C)CCCCCC(Br)c1ccccc1Cl
Temperature: 15 °C
Yield: 81.8 %

Procedure:
8-(2-Chlorophenyl)-2,2-dimethyl-oct-7-enoic acid ethyl ester (7 g, 22.8 mmol) was dissolved in glacial acetic acid (60 mL). The solution was cooled in an ice-bath (ca. 15° C.), while dry hydrogen bromide was passed into the solution for 8 h. The reaction mixture was poured into ice-water (130 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with saturated NaHCO3 solution (100 mL), dried over Na2SO4, and concentrated under reduced pressure. The crude product (10 g) was purified by column chromatography (200 g silica gel, eluting with ethyl acetate/heptane=1/20 to 1/10) to furnish 8-bromo-8-(2-chlorophenyl)2,2-dimethyloctanoic acid ethyl ester (7.46 g, 81.8% yield) as a yellow oil. 1H NMR (Field: 300 MHz, Solvent: CDCl3/TMS) δ (ppm): 7.59 (d, 1H, J=7.8 Hz), 7.34 (t, 1H, J=7.5 Hz), 7.26 (d, 1H, J=6.9 Hz), 7.19 (t, 1H, J=7.2 Hz), 5.45 (t, 1H, J=7.5 Hz), 4.09 (q, 2H, J=7.2 Hz), 2.26-2.09 (m, 4H), 1.52-1.46 (m, 2H), 1.41-1.31 (m, 2H), 1.28-1.18 (m, 2H), 1.20 (t, 3H, J=7.2 Hz), 1.14 (s, 6H). 13C NMR (Field: 75 MHz, Solvent: CDCl3/TMS) δ (ppm): 177.80, 139.43, 132.65, 129.64, 129.24, 128.88, 127.45, 60.28, 50.30, 42.25, 39.21, 29.48, 27.98, 25.36, 24.88, 14.49. HRMS (GC-CI): Calculated for C18H26BrClO2 (M+H)+389.0883, found 389.0867.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([O:12]C)[CH:8]=[CH:9][C:10]=1[OH:11])([CH3:4])([CH3:3])[CH3:2].S(=O)(=O)(O)O.[C:19](O)(=[O:21])[CH3:20]>>[C:19]([O:11][C:10]1[CH:9]=[CH:8][C:7]([OH:12])=[CH:6][C:5]=1[C:1]([CH3:2])([CH3:3])[CH3:4])(=[O:21])[CH3:20]
Reactant: COc1ccc(O)c(C(C)(C)C)c1
Reactant: CC(=O)O
Agent: O=S(=O)(O)O
Product: CC(=O)Oc1ccc(O)cc1C(C)(C)C
Temperature: 25 °C
Reaction time: 144 h

Procedure:
To 36 g of 3-t-butyl-4-hydroxyanisole dissolved in 100 ml of anhydrous acetic acid was added a catalytic amount of concentrated sulfuric acid and the mixture was stirred at room temperature for 6 days. After the reaction solution was concentrated under reduced pressure, the concentrate was dissolved in 200 ml of acetonitrile and combined with 60 g of sodium iodide. To the resulting solution was added dropwise 51 ml of trimethylsilyl chloride at room temperature and then the mixture was heated under reflux for 3 hours. The reaction mixture was allowed to attain room temperature, and then concentrated under reduced pressure, combined with water and extracted with ethyl acetate. The extracted layers were washed with saturated brine, then dried over anhydrous magnesium sulfate and concentrated to give 47.0 g of 4-acetoxy-3-t-butylphenol as a colorless oil (quantitative).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH:10]=[CH:9][S:8][C:6]=2[N:7]=1.[CH3:12][NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(O)C>[Cl:1][C:2]1[N:3]=[C:4]([N:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH3:12])[C:5]2[CH:10]=[CH:9][S:8][C:6]=2[N:7]=1
Reactant: Clc1nc(Cl)c2ccsc2n1
Reactant: CNc1ccccc1
Solvent: CCO
Product: CN(c1ccccc1)c1nc(Cl)nc2sccc12

Procedure:
2,4-Dichlorothieno[2,3-d]pyrimidine (4.5 g, 0.022 mol) and N-methylaniline (4.7 g, 0.044 mol) in ethanol (50 ml) were stirred at room temperature for 72 hours. The solid obtained was collected by filtration, washed with ethanol and dried, 5.15 g. Recrystallization from ethyl acetate gave the title compound, m.p. 167°-168°.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][C:5]1[N:6]([CH2:18][CH2:19][O:20][CH2:21][CH2:22][NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:17]=1.ClC1C=C(C=CC=1)C(OO)=[O:36]>C(Cl)(Cl)Cl>[CH3:1][O:2][CH2:3][CH2:4][C:5]1[N:6]([CH2:18][CH2:19][O:20][CH2:21][CH2:22][NH:23][C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:29])[CH3:28])[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N+:10]([O-:36])=[CH:9][C:8]=2[N:17]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COCCc1nc2cnc3ccccc3c2n1CCOCCNC(=O)OC(C)(C)C
Solvent: ClC(Cl)Cl
Product: COCCc1nc2c[n+]([O-])c3ccccc3c2n1CCOCCNC(=O)OC(C)(C)C
Reaction time: 0.5 h
Yield: 99.7 %

Procedure:
A solution of tert-butyl 2-{2-[2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethoxy}ethylcarbamate (10.22 g, 24.7 mmol) in 250 mL of CHCl3 was treated with 3-chloroperoxybenzoic acid (MCPBA, 77%, 9.12 g, 40.8 mmol). After stirring 30 min, the reaction mixture was washed with 1% Na2CO3 solution (2×75 mL) and brine. The organic layer was then dried over Na2SO4 and concentrated to give 10.6 g of tert-butyl 2-{2-[2-(2-methoxyethyl)-5-oxido-1H-imidazo[4,5-c]quinolin-1-yl]ethoxy}ethylcarbamate as an orange foam that was used without further purification.
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH2:12][O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:6][CH:5]=1.[CH2:21]=[C:22]1[O:26][C:24](=[O:25])[CH2:23]1>>[CH2:14]([O:13][CH2:12][CH2:11][O:10][C:7]1[CH:8]=[CH:9][C:4]([CH2:3][CH2:2][O:1][C:24](=[O:25])[CH2:23][C:22]([CH3:21])=[O:26])=[CH:5][CH:6]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: OCCc1ccc(OCCOCc2ccccc2)cc1
Reactant: C=C1CC(=O)O1
Product: CC(=O)CC(=O)OCCc1ccc(OCCOCc2ccccc2)cc1

Procedure:
Diketene (3-buteno-β-lactone, available, e.g., from Aldrich Chemical Co.) is then added to the hydroxyalkylbenzene derivative 4 under basic conditions, e.g., using triethylamine in dimethoxyethane (DME) to form a ω-phenylalkylacetoacetate derivative (5). For example, 1-(2-hydroxyethyl)-4-(2-benzyloxyethoxy)benzene is reacted with diketene to afford 2-[4-(2-benzyloxyethoxy)phenyl]ethylacetoacetate (5). (Step 5.)
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:29])[C:5]([C:25]([F:28])([F:27])[F:26])([O:20][Si](C)(C)C)[CH2:6][C:7]([C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([F:17])[C:11]=1[O:18][CH3:19])([CH3:9])[CH3:8])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>O1CCCC1>[CH2:1]([O:3][C:4](=[O:29])[C:5]([C:25]([F:27])([F:26])[F:28])([OH:20])[CH2:6][C:7]([C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([F:17])[C:11]=1[O:18][CH3:19])([CH3:9])[CH3:8])[CH3:2]
Reactant: CCOC(=O)C(CC(C)(C)c1ccc(Cl)c(F)c1OC)(O[Si](C)(C)C)C(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)C(O)(CC(C)(C)c1ccc(Cl)c(F)c1OC)C(F)(F)F
Temperature: 25 °C
Yield: 77.4 %

Procedure:
4.71 g (10.26 mmol) of (rac.) 4-(4-chloro-3-fluoro-2-methoxyphenyl)-4-methyl-2-(trifluoromethyl)-2-trimethylsilyloxy-pentanoic acid ethyl ester is dissolved in 57 ml of tetrahydrofuran and mixed with 3.24 g (10.26 mmol) of tetrabutylammonium fluoride: after stirring over the weekend at room temperature, the reaction mixture is mixed with water and extracted three times with methyl tert-butyl ether. The combined organic extracts are washed with brine. After the drying, the solvent is spun off, and the remaining residue is chromatographed on silica gel (mobile solvent:ethyl acetate/hexane). 3.07 g (77.4%) of the desired compound is isolated.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[CH:5]=[CH:6][C:7]1[C:8]([C:13]([OH:15])=[O:14])=[CH:9][CH:10]=[CH:11][CH:12]=1.[CH3:19]N(C)C=O>[Pd]>[C:13]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[CH2:6][CH2:5][CH2:4][CH2:3][C:2]1[CH:1]=[CH:19][CH:16]=[CH:17][CH:18]=1)([OH:15])=[O:14]
Reactant: CN(C)C=O
Reactant: Cc1cccc(C=Cc2ccccc2C(=O)O)c1
Agent: [Pd]
Product: O=C(O)c1ccccc1CCCCc1ccccc1

Procedure:
A solution of 53.0 gm. of 3'-methylstilbene-2-carboxylic acid in 230 ml. dimethylformamide containing 2.0 gm. of 5% palladium on carbon is hydrogenated in a Parr shaker at 60 p.s.i. for 11/2 hours. The solution is filtered and added to ether and water. The organic layer is washed with water, then dried and evaporated. The product is recrystallized from ether-hexane to give 48 gm., 90%, of 3-(o-carboxyphenethyl)toluene,m.p. 82°-84° C. Use of 3'-ethylenestilbene-2-carboxylic acid gives a similar yield of 3-(o-carboxyphenethyl)ethylbenzene.
Reaction SMILES: [OH:1][CH:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C:3]([OH:5])=[O:4].CC(C)([O-])C.[K+].[CH2:28](Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CN(C=O)C>[OH:1][CH:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C:3]([O:5][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:4]
Reactant: CCCCCCCCCCCCCCCCC(O)C(=O)O
Reactant: BrCc1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCCCC(O)C(=O)OCc1ccccc1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
To a stirred solution of DL-2-hydroxystearic acid (3.0 g, 10 mmole) in 20 ml dry DMF was added potassium tert-butoxide (1.23 g, 11 mmole) and the mixture was stirred for one hour at 60° C. Benzyl bromide (2.14 g, 12.5 mmole) was added and the mixture was stirred for six hours at 80° C. The mixture was evaporated under reduced pressure and 100 ml ethyl acatate was added. The organic phase was separated and washed four times with water. The organic phase was dried with sodium sulfate and concentrated in vacuo. The product was isolated by silica gel column chromatography. Yield: 3.3 g
Reaction SMILES: [Cl:1][C:2]1[C:3]([N:11]([CH2:15][CH2:16][CH3:17])[CH2:12][CH2:13][CH3:14])=[N:4][NH:5][C:6]=1[C:7]([F:10])([F:9])[F:8].F[C:19]1[CH:34]=[CH:33][C:22]([C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])=[CH:21][C:20]=1[C:35]([O:37][CH2:38][CH3:39])=[O:36]>>[Cl:1][C:2]1[C:3]([N:11]([CH2:15][CH2:16][CH3:17])[CH2:12][CH2:13][CH3:14])=[N:4][N:5]([C:19]2[CH:34]=[CH:33][C:22]([C:23]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[O:24])=[CH:21][C:20]=2[C:35]([O:37][CH2:38][CH3:39])=[O:36])[C:6]=1[C:7]([F:9])([F:8])[F:10]
Reactant: CCOC(=O)c1cc(C(=O)OCc2ccccc2)ccc1F
Reactant: CCCN(CCC)c1n[nH]c(C(F)(F)F)c1Cl
Product: CCCN(CCC)c1nn(-c2ccc(C(=O)OCc3ccccc3)cc2C(=O)OCC)c(C(F)(F)F)c1Cl
Yield: 47 %

Procedure:
Following a procedure analogous to that for the synthesis of Intermediate 1E, 4-chloro-N,N-dipropyl-5-(trifluoromethyl)-1H-pyrazol-3-amine (287 mg, 1.06 mmol) and 1-benzyl 3-ethyl 4-fluoroisophthalate (Intermediate 91B, 268 mg, 0.89 mmol) were converted to the title compound (231 mg, 47%). MS(ESI+) m/z 552.3 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[CH:8][C:7](F)=[C:6]([C:11]#[N:12])[CH:5]=1.Cl.[CH3:15][NH:16][CH3:17].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[CH:8][C:7]([N:16]([CH3:17])[CH3:15])=[C:6]([C:11]#[N:12])[CH:5]=1
Reactant: CNC
Reactant: COC(=O)c1ccc(F)c(C#N)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: COC(=O)c1ccc(N(C)C)c(C#N)c1
Yield: 94 %

Procedure:
To a stirred solution of 24.0 g (134 mmol) 2 and 240 ml dimethylsulphoxid were added 13.2 g (161 mmol) dimethylamine hydrochloride and 38.9 g (281 mmol) potassium carbonate. The reaction mixture was stirred over night and was reduced with high vacuum rotation evaporator at 65° C. The residue was diluted with dichloromethane, washed twice with water. The combined water phases were extracted with dichloromethane. The combined dichloromethane phases were washed with diluted sodium hydrogen carbonate solution, dried with sodium sulphate and concentrated. The oily crude product 3 was obtained in 94% yield (25.7 g, 126 mmol) and was used for the next step without purification.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[CH2:10][CH2:9][N:8]([Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[C:5]2=[N:6][CH:7]=1.C([Li])(C)(C)C.CCCCC.[C:28](=[O:30])=[O:29]>CCOCC>[C:14]([Si:11]([CH3:13])([CH3:12])[N:8]1[C:5]2=[N:6][CH:7]=[C:2]([C:28]([OH:30])=[O:29])[CH:3]=[C:4]2[CH2:10][CH2:9]1)([CH3:17])([CH3:16])[CH3:15]
Reactant: O=C=O
Reactant: CC(C)(C)[Si](C)(C)N1CCc2cc(Br)cnc21
Agent: [Li]C(C)(C)C
Solvent: CCOCC
Solvent: CCCCC
Product: CC(C)(C)[Si](C)(C)N1CCc2cc(C(=O)O)cnc21
Temperature: 25 °C
Reaction time: 0.67 h

Procedure:
To a stirred and cooled (−78° C.) solution of the bromide 4 (205 mg, 0.65 mmol) in Et2O (4 mL) was added dropwise a 1.5 M solution of tert-butyllithium in pentane (0.92 mL, 1.37 mmol). After 40 min., dry gaseous CO2 was introduced into the reaction vessel. Progress of the reaction was followed by TLC analysis. After complete consumption of starting material 4 the reaction was quenched by the addition of saturated aqueous NaHCO3 solution. The mixture was allowed to warm to room temperature, and diluted with CH2Cl2. The aqueous layer was extracted with CH2Cl2 (2×), and the combined organic solutions were dried (MgSO4), filtered and concentrated. The residual yellow oil was dissolved in CH2Cl2:MeOH=20:1 and filtered through silicagel pad. The filtrate was concentrated and used directly in the next step.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:24]([F:27])([F:26])[F:25])=[C:13]2[C:17]=1[N:16]([CH3:18])[C:15]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:14]2)C1C=CC=CC=1>[Pd].C(O)C>[OH:8][C:9]1[CH:10]=[CH:11][C:12]([C:24]([F:27])([F:25])[F:26])=[C:13]2[C:17]=1[N:16]([CH3:18])[C:15]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:14]2
Reactant: CCOC(=O)c1cc2c(C(F)(F)F)ccc(OCc3ccccc3)c2n1C
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)c1cc2c(C(F)(F)F)ccc(O)c2n1C

Procedure:
The reaction was carried out in a manner similar to Reference Example 18 b) except for using 6.50 g (17.2 mmol) of ethyl 7-benzyloxy-1-methyl-4-trifluoromethyl-2-indolecarboxylate, 1.0 g of 10% palladium/carbon and 150 ml of ethanol. Ethyl 7-hydroxy-1-methyl-4-trifluoromethyl-2-indolecarboxylate was thus obtained in the yield of 4.95 g (97.0%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[CH:6]=[C:5]2[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=1.[CH3:21][C:22]1[N:27]=[CH:26][C:25]([C:28]([C:30]2[N:31]([CH3:35])[CH:32]=[N:33][CH:34]=2)=[O:29])=[CH:24][CH:23]=1>>[Cl:20][C:16]1[CH:15]=[C:14]([C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:28]([C:25]4[CH:26]=[N:27][C:22]([CH3:21])=[CH:23][CH:24]=4)([C:30]4[N:31]([CH3:35])[CH:32]=[N:33][CH:34]=4)[OH:29])[CH:3]=3)[N:8]=[C:7]([O:12][CH3:13])[CH:6]=2)[CH:19]=[CH:18][CH:17]=1
Reactant: Cc1ccc(C(=O)c2cncn2C)cn1
Reactant: COc1cc(-c2cccc(Cl)c2)c2cc(Br)ccc2n1
Product: COc1cc(-c2cccc(Cl)c2)c2cc(C(O)(c3ccc(C)nc3)c3cncn3C)ccc2n1
Yield: 48 %

Procedure:
Following the same procedure as that described in Example 1E, 6-bromo-4-(3-chloro-phenyl)-2-methoxy-quinoline (0.200 g, 0.574 mmol) and (6-methyl-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methanone (0.105 g, 0.522 mmol) generated 0.118 g (48% yield) of [4-(3-chloro-phenyl)-2-methoxy-quinolin-6-yl]-(6-methyl-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methanol.
Reaction SMILES: [OH:1][CH:2]([C:28]1[CH:33]=[CH:32][C:31]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([NH:42][CH3:43])=[O:41])[CH:35]=2)=[CH:30][CH:29]=1)[CH2:3][C:4]1[N:5]=[CH:6][N:7](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:8]=1.Cl>[C].[Pd]>[OH:1][CH:2]([C:28]1[CH:29]=[CH:30][C:31]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([NH:42][CH3:43])=[O:41])[CH:35]=2)=[CH:32][CH:33]=1)[CH2:3][C:4]1[N:5]=[CH:6][NH:7][CH:8]=1
Reactant: CNC(=O)c1cccc(-c2ccc(C(O)Cc3cn(C(c4ccccc4)(c4ccccc4)c4ccccc4)cn3)cc2)c1
Agent: [Pd]
Agent: Cl
Product: CNC(=O)c1cccc(-c2ccc(C(O)Cc3c[nH]cn3)cc2)c1
Yield: 47.9 %

Procedure:
By the reaction in the same manner as in Example 41-(ii) using [4′-[1-hydroxy-(1-trityl-1H-imidazol-4-yl)ethyl]-N-methyl[1,1′-biphenyl]-3-carboxamide (527 mg), 10% palladium carbon (527 mg) and 1N hydrochloric acid (0.935 ml), the title compound (144 mg) was obtained as colorless powder crystals.
Reaction SMILES: Br[C:2]1[C:3]2[N:4]([N:8]=[C:9]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:20]([O:24][C:25]([N:27]1[CH2:28][CH:29]=[C:30]([C:2]2[C:3]3[N:4]([N:8]=[C:9]([NH:11][C:12]4[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=4)[N:10]=3)[CH:5]=[CH:6][CH:7]=2)[CH2:31][CH2:32]1)=[O:26])([CH3:23])([CH3:21])[CH3:22]
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Reactant: COc1ccc(Nc2nc3c(Br)cccn3n2)cc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Product: COc1ccc(Nc2nc3c(C4=CCN(C(=O)OC(C)(C)C)CC4)cccn3n2)cc1

Procedure:
4-[2-(4-Methoxy-phenylamino)-[1,2,4]triazolo[1,5-a]pyridin-8-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester was prepared from (8-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-yl)-(4-methoxy-phenyl)-amine (150.0 mg, 0.4700 mmol) and 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (160.0 mg, 0.5174 mmol) with Pd(dppf)Cl2 (0.035 g) as the catalyst in a manner analogous to Step 19e. The reaction product was isolated as a clear viscous oil. 1H NMR (400 MHz, CDCl3, δ, ppm): 8.30 (dd, J=6.6, 1.0 Hz, 1H), 7.52-7.47 (m, 2H), 7.33-7.29 (m, 1H), 7.25-7.20 (m, 1H), 6.94-6.89 (m, 2H), 6.84 (dd, J=7.3, 7.3 Hz, 1H), 6.63 (s, 1H), 4.23-4.19 (m, 2H), 3.81 (s, 3H), 3.73-3.67 (m, 2H), 2.69-2.62 (m, 2H), 1.50 (s, 9H). MS=422 (MH)+.
Reaction SMILES: C[Si]([Cl:5])(C)C.[OH-].[CH:7]1([Sn+:13]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1>>[CH:20]1([Sn:13]([Cl:5])([CH:7]2[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]2)[CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1
Reactant: C[Si](C)(C)Cl
Reactant: C1CCC([Sn+](C2CCCCC2)C2CCCCC2)CC1
Agent: [OH-]
Product: Cl[Sn](C1CCCCC1)(C1CCCCC1)C1CCCCC1

Procedure:
In a 500 mL three-necked flask, trimethylsilyl chloride (170 g, 109 mmol) was added to tricyclohexyltin hydroxide (80 g, 133 mmol) and heated at reflux during 18 hours. After distillation of trimethylsilyl chloride in excess and hexamethyldisiloxane under reduced pressure, the crude product was recrystallized in petroleum ether. White needles were obtained (39.82 g, 79.6 mmol).
Reaction SMILES: [NH:1]([C@H:3]1[C@@H:7]([CH3:8])[CH2:6][N:5]([O:9]CC2C=CC=CC=2)[C:4]1=[O:17])N.C(O)(=O)C>C(O)C.[Pd]>[NH2:1][C@H:3]1[C@@H:7]([CH3:8])[CH2:6][N:5]([OH:9])[C:4]1=[O:17]
Reactant: C[C@H]1CN(OCc2ccccc2)C(=O)[C@H]1NN
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CCO
Product: C[C@H]1CN(O)C(=O)[C@H]1N
Yield: 24.6 %

Procedure:
The hydrazine from step C (69 mg) was dissolved in ethanol (20 ml) and glacial acetic acid (5 ml) and the solution was hydrogenated at 50 psi for 2 h in the presence of palladium black (50 mg). The solution was filtered and further hydrogenated in the presence of platinum oxide (50 mg) at 50 psi for 1.5 h. The solution was filtered and the solvent evaporated to dryness. The residue was dissolved in water (10 ml) and applied to a column containing Dowex 50W-X8 (100-200 mesh, 2×2cm, H+ form). After washing the resin with water (3×15 ml) the product was eluted with dilute aqueous ammonia solution. The fractions containing the product were freeze dried to give cis-3-amino-1-hydroxy-4-methylpyrrolidin-2-one (9.4 mg). 1H NMR (250 MHz, D2O) δ3.91 (1H; d, J=8.09 Hz; CO--CH--N), 3.78 (1 H; dd, Jgem =10.0 Hz, J=7.OO Hz; CHHD AHBN), 3.23 (1H; dd, Jgem =10.1 Hz, J=3.0 Hz; CHAHBN ), 2.79-2.69 (1H; m; CHCH3), 1.10 (3H; d, J=7.22 Hz, CH3). Irradiation of the signal at 2.79ppm gave an NOE to the signals at 3.91 and 3.78, confirming the cis geometry. (m/e: theory, 130.0742; found, 130.0749).
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:18])[C:5]1[CH:10]=[CH:9][C:8]([CH2:11][NH:12][CH2:13][CH:14]([OH:17])[CH2:15][CH3:16])=[CH:7][CH:6]=1.[C:19]([C:27]1[CH:35]=[C:34]([Cl:36])[CH:33]=[CH:32][C:28]=1[C:29](O)=[O:30])(=O)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[CH3:2][O:3][C:4](=[O:18])[C:5]1[CH:6]=[CH:7][C:8]([CH2:11][N:12]2[C:13]([C:14](=[O:17])[CH2:15][CH3:16])=[C:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:27]3[C:28](=[CH:32][CH:33]=[C:34]([Cl:36])[CH:35]=3)[C:29]2=[O:30])=[CH:9][CH:10]=1
Reactant: O=C(O)c1ccc(Cl)cc1C(=O)c1ccccc1
Reactant: CCC(O)CNCc1ccc(C(=O)OC)cc1
Agent: Cl
Product: CCC(=O)c1c(-c2ccccc2)c2cc(Cl)ccc2c(=O)n1Cc1ccc(C(=O)OC)cc1

Procedure:
In the same manner as in Example 458, Step 2, the title compound was synthesized from 4-[(2-hydroxybutylamino)methyl]benzoic acid methyl ester hydrochloride and 2-benzoyl-4-chlorobenzoic acid.