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]octane-1-carboxylate

HRID 908125노트

반응식

HRID 908125 반응식
Br[C:2]([CH3:24])([CH3:23])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]23[CH2:18][CH2:17][C:14]([C:19]([O:21][CH3:22])=[O:20])([CH2:15][CH2:16]2)[CH2:13][CH2:12]3)=[CH:7][CH:6]=1)=O.[NH2:25][C:26]1[C:27]([OH:33])=[N:28][CH:29]=[N:30][C:31]=1[NH2:32].Cl>CCO>[NH2:32][C:31]1[C:26]2[N:25]=[C:3]([C:5]3[CH:6]=[CH:7][C:8]([C:11]45[CH2:18][CH2:17][C:14]([C:19]([O:21][CH3:22])=[O:20])([CH2:15][CH2:16]4)[CH2:13][CH2:12]5)=[CH:9][CH:10]=3)[C:2]([CH3:23])([CH3:24])[O:33][C:27]=2[N:28]=[CH:29][N:30]=1

참가 물질

5

반응물 3

HCID 313Hydrochloric AcidHCID 25258105Methyl 4-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[2.2.2]octane-1-carboxylate2회HCID 178508814HCID 178508814, 화합물

생성물 1

HCID 25258106methyl 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

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

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.

후처리

  1. temperatureThe suspension was heated
  2. temperatureunder reflux overnight
  3. customevaporated to dryness
  4. additionThe residue treated with 2M potassium carbonate solution
  5. extractionthe mixture was extracted into EtOAc (4×50 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-7abce318962241598c0634cee757424a
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08017603B2

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