Tetrahydrofuran → methyl(2R)-2-methyl-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propanoate

Participants

Reaction Steps

N-[3-(2-Bromo-1,3-thiazol-5-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine (INTERMEDIATE 9, 1.50 g, 3.61 mmol), Pd(OAc)2 (81 mg, 0.361 mmol), and 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (297 mg, 0.722 mmol) were combined in a vial, sealed, and purged with nitrogen (2×). Degassed THF (15 mL) and (S)-(−)-3-methoxy-2-methyl-3-oxopropylzinc bromide (0.5 M in THF, 28.9 mL, 14.45 mmol) were added, and the reaction was stirred at room temperature overnight. The reaction was diluted with saturated aqueous NH4Cl and water and extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. Flash chromatography (0-50% ethyl acetate in hexanes) afforded methyl (2R)-2-methyl-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]propanoate (1.37 g, 87%) as a yellow gum. MS ESI: [M+H]+ m/z 437.0. 1H NMR (600 MHz, DMSO-d6) δ 10.23 (s, 1H), 8.80 (d, J=4.8, 1H), 7.93 (s, 2H), 7.43 (s, 1H), 7.25 (d, J=4.9, 1H), 7.12 (s, 1H), 3.58 (s, 3H), 3.25 (dd, J=7.8, 15.2, 1H), 3.09 (dd, J=6.2, 15.2, 1H), 3.00-2.91 (m, 1H), 2.29 (s, 3H), 1.15 (d, J=7.0, 3H). rhSYK activity=+++

Provenance & Evidence