Methanol → Methyl 5-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}pyridine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

The product of Step 1 (175 mg, 0.326 mmol), palladium (II) acetate (7.32 mg, 0.033 mmol), and 1,3-bis(diphenylphosphino)propane (13.46 mg, 0.033 mmol) were combined in a 5 ml microwave vial, sealed, and taken up in DMF (3 ml)/MeOH (1.5 ml). CO was bubbled through the reaction mixture for 5 min. Triethylamine (0.091 ml, 0.653 mmol) was added, a CO balloon was attached, and the reaction was stirred at 70° C. overnight. The reaction was diluted with saturated NH4Cl solution and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), and evaporated. The crude material was purified by chromatography on silica gel (Biotage 25 g SNAP, 50-100% EtOAc/hexanes, 50-100% EtOAc/toluene) followed by reverse phase HPLC (45-80% MeCN/water w/0.1% TFA). The fractions containing the desired product were combined, partially concentrated to remove MeCN, diluted with saturated NaHCO3, and extracted with CH2Cl2 (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated to provide methyl 5-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}pyridine-2-carboxylate (111 mg, 0.215 mmol, 66% yield) as a colorless foam. MS ESI: [M+H]+ m/z 516.1.

Provenance & Evidence