Sodium Hydroxide → (4-(4-(4-Amino-7,7-dimethyl-7H-pyrimido(4,5-b)(1,4)oxazin-6-yl)phenyl)bicyclo(2.2.2)oct-1-yl)acetic Acid

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl {4-[4-(4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]bicyclo[2.2.2]oct-1-yl}acetate (Intermediate 10; 601 mg, 1.38 mmol) in MeOH (40 mL) and THF (40 mL) was added 2M NaOH solution (3.5 mL, 6.9 mmol). The reaction mixture was stirred at 60° C. overnight, the organic solvent was concentrated and the residue acidified with 2M HCl to pH 2. The suspension was filtered and the solid purified by reverse phase chromatography loading in DMSO/MeCN/H2O (7:2:1) with a few drops of concentrated ammonia solution and eluting 5-95% water (+0.5% NH3)-MeCN. The title compound was isolated as a white solid (302 mg, 0.717 mmol, 52%.

Provenance & Evidence