تفاعل #2440265

معادلة التفاعل

HCl

methyl 4-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[2.2.2]octane-1-carboxylate

Intermediate 26

methyl 4-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[2.2.2]octane-1-carboxylate

5,6-diaminopyrimidin-4-ol

→

title compound

Methyl 4-[4-(4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]bicyclo[2.2.2]octane-1-carboxylate

المذيبات

EtOH

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe suspension was heated
2. 2
   درجة الحرارةunder reflux overnight
3. 3
   أخرىevaporated to dryness
4. 4
   workup.ADDITIONThe residue treated with 2M potassium carbonate solution
5. 5
   استخلاصthe mixture was extracted into EtOAc (4×50 mL)
6. 6
   تجفيفdried (MgSO4)
7. 7
   تركيزconcentrated

الإجراء التجريبي

To a solution of methyl 4-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[2.2.2]octane-1-carboxylate (Intermediate 26; 507 mg, 1.29 mmol) in abs EtOH (10 mL) was added 5,6-diaminopyrimidin-4-ol (179 mg, 1.42 mmol) followed by 1M HCl (1.4 mL). The suspension was heated under reflux overnight, the reaction mixture was allowed to cool to ambient temperature and then evaporated to dryness. The residue treated with 2M potassium carbonate solution to adjust the pH to 10 and then the mixture was extracted into EtOAc (4×50 mL). The organic extracts were combined, dried (MgSO4) and concentrated to leave the title compound as a yellow gum which was purified on a 12 g Redisep silica cartridge, dry loading the sample on Merck silica (deactivated, ˜1 g) and eluting with DCM-MeOH 0-2%-5% to provide the title compound 150 mg (0.357 mmol, 27%); 1H NMR δ 1.61 (s, 6H), 1.84 (s, 12H), 3.61 (s, 3H), 6.98 (s, 2H), 7.41 (d, 2H), 7.66 (d, 2H), 7.95 (s, 1H); MS m/e MH+ 421.

المصدر