تفاعل #995297

معادلة التفاعل

5,6-diaminopyrimidin-4-ol

HCl

methyl {4-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[2.2.2]oct-1-yl}acetate

Intermediate 9

methyl {4-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[2.2.2]oct-1-yl}acetate

→

title compound

المردود 64.2%

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

المردود 64.2%

المذيبات

water

ethanol

EtOH

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةto cool to ambient temperature
2. 2
   أخرىevaporated to dryness
3. 3
   workup.ADDITIONthe residue treated with 2M NaOH
4. 4
   ترشيحThe resulting suspension was filtered
5. 5
   أخرىto provide a yellow solid which
6. 6
   أخرىwas purified on a 12 g presearch silica cartridge
7. 7
   أخرىdry loading on silica (2 g)
8. 8
   غسيلeluting with 0-2.5-5% MeOH-DCM

الإجراء التجريبي

To a solution of 5,6-diaminopyrimidin-4-ol (280 mg, 2.2 mmol) in water (8 mL), absolute ethanol (25 mL) and 1M HCl (2.2 mL, 2.2 mmol) was added a solution of methyl {4-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[2.2.2]oct-1-yl}acetate (Intermediate 9; 877 mg, 2.15 mmol) in absolute EtOH (80 mL). The solution was heated to 100° C. overnight then allowed to cool to ambient temperature, evaporated to dryness, and the residue treated with 2M NaOH to adjust the pH to 10. The resulting suspension was filtered to provide a yellow solid which was purified on a 12 g presearch silica cartridge dry loading on silica (2 g) and eluting with 0-2.5-5% MeOH-DCM to provide the title compound as a white solid (601 mg, 1.38 mmol, 64%)1H NMR δ 1.59-1.63 (12H, m), 1.79-1.83 (6H, m), 2.16 (2H, s), 3.59 (3H, s), 6.91 (2H, s), 7.39 (2H, d), 7.64 (2H, d), 7.95 (1H, s); MS m/e MH+ 435.

المصدر