Potassium Carbonate → Ethyl 2-[3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]-1,3-thiazole-4-carboxylate

HRID 1986456Notes

Reaction equation

[CH2:1]([C:5]1[C:14]([CH2:15][NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[C:13]([C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10](OS(C(F)(F)F)(=O)=O)[CH:11]=2)[N:6]=1)[CH:2]([CH3:4])[CH3:3].[B].[C:40]([O-])(=O)[CH3:41].[K+].Cl[C:46]1[S:47][CH:48]=[CH:49][N:50]=1.[C:51](=[O:54])([O-])[O-:52].[K+].[K+]>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].ClCCl.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.C1(C)C=CC=CC=1.C(O)C.CS(C)=O>[C:19]([O:18][C:17]([NH:16][CH2:15][C:14]1[C:5]([CH2:1][CH:2]([CH3:4])[CH3:3])=[N:6][C:7]2[C:12]([C:13]=1[C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=1)=[CH:11][C:10]([C:46]1[S:47][CH:48]=[C:49]([C:51]([O:52][CH2:40][CH3:41])=[O:54])[N:50]=1)=[CH:9][CH:8]=2)=[O:23])([CH3:21])([CH3:20])[CH3:22]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of tert-butyl [2-isobutyl-4-(4-methylphenyl)-6-trifluoromethanesulfonyloxy-quinolin-3-yl]methylcarbamate (2.76 g, 5.0 mmol), boron bispinacolate (1.52 g, 6.0 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium-dichloromethane (1:1) complex (0.11 g, 0.15 mmol), potassium acetate (1.47 g, 7.5 mmol) and dimethyl sulfoxide (30 ml) was stirred under an argon atmosphere at 100° C. for 2 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and a mixture of the residue, 2-chlorothiazole (0.96 g, 5.0 mmol), tetrakis(triphenylphosphine)palladium (0.58 g, 0.5 mmol), potassium carbonate (3.46 g, 25 mmol), ethanol (5 ml), toluene (30 ml) and water (5 ml) was stirred under an argon atmosphere at 100° C. for 10 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed 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 ethyl 2-[3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]-1,3-thiazole-4-carboxylate as a mixture. To a solution of the obtained mixture in tetrahydrofuran (4 ml) was added 4N solution of hydrogen chloride in 1,4-dioxane (4 ml), and the mixture was stirred at room temperature for 4 hrs. The reaction mixture was concentrated under reduced pressure, poured into 5% aqueous potassium carbonate solution (100 ml) and extracted with ethyl acetate. The extract was washed 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 ethyl 2-[3-(aminomethyl)-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]-1,3-thiazole-4-carboxylate (0.08 g, yield 15%) as white crystals.

Workup

extractionextracted with ethyl acetate
washThe extract was washed with saturated brine
dry with materialdried over anhydrous magnesium sulfate
customThe solvent was evaporated under reduced pressure
stirringwas stirred under an argon atmosphere at 100° C. for 10 hrs
extractionextracted with ethyl acetate
washThe extract was washed with saturated brine
dry with materialdried over anhydrous magnesium sulfate
customThe solvent was evaporated under reduced pressure
customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-5215211b21634aa6a85a90c88b1d38dd
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07547710B2

Reaction notes

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