Sodium Hydroxide → {5-[4-(4-Amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]bicyclo[3.2.2]non-1-yl}acetic Acid

Participants

Reaction Steps

To a solution of methyl {5-[4-(4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]bicyclo[3.2.2]non-1-yl}acetate (Intermediate 25; 55 mg, 0.12 mmol) in MeOH (5 mL) was added 2M NaOH (0.3 mL) and the reaction mixture was allowed to stir at ambient temperature overnight, then at 50° C. for 8 hrs and ambient temperature overnight. The solvent was removed under reduced pressure and the residue was acidified to pH 2 with 2M HCl, the filtrate extracted into EtOAc (2×50 mL), the organic extracts combined, dried (MgSO4) and concentrated to leave a yellow gum. The product was purified by reverse phase preparative HPLC, loading the sample in DMSO/MeCN/H2O (7:2:1) and eluting with 5-95 water-MeCN with 0.2% TFA in each phase, to provide the title compound (31 mg, 0.0714 mmol, 59%) as a pale yellow solid, 1H NMR δ 1.34-1.56 (14H, m), 1.63 (6H, s), 1.95 (2H, s), 7.15 (2H, d), 7.63-7.66 (2H, m), 8.02 (1H, s); MS m/e MH+ 435

Provenance & Evidence