Hydrochloric Acid → 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

Participants

Reaction Steps

To a solution of methyl {4-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[2.2.2]oct-1-yl}acetate (648 mg, 1.59 mmol) in absolute EtOH (15 mL) was added 5,6-diaminopyrimidin-4-ol (221 mg, 1.75 mmol) followed by 1M HCl (1.75 mL). The reaction mixture was heated under reflux overnight then allowed to cool to ambient temperature and evaporated to dryness. The residue was treated with 2M NaOH to adjust the pH to 11 and then the mixture was extracted into EtOAc (4×50 mL). The organic extracts were combined, dried (MgSO4) and concentrated to leave the crude ester product. The aqueous phase was acidified with 2M HCl and then re extracted with EtOAc (2×100 mL), the organic extracts were combined, dried (MgSO4) and concentrated to give some of the corresponding acid {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 (40 mg, 0.095 mmol, 6%). The ester was purified on a 12 g silica redisep cartridge dry loading the sample on celite and eluting with DCM-MeOH 0-2%-5% using an Isco Companion to provide the title compound as a solid 122 mg (0.281 mmol, 17.6%);

Provenance & Evidence