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 2353083Notes

Reaction equation

HRID 2353083 reaction equation
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

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 25258105Methyl 4-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[2.2.2]octane-1-carboxylate2×HCID 178508814HCID 178508814, compound

Product 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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-3bcbbf3e14c54a179bf15ae355ba642c
Source dataset
uspto-grants-2010_07
Patent number
US07749997B2

Reaction notes

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