Hydrochloric Acid → methyl {5-[4-(4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]bicyclo[3.2.2]non-1-yl}acetate

HRID 2353081Notes

Reaction equation

HRID 2353081 reaction equation
Br[C:2]([CH3:26])([CH3:25])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]23[CH2:19][CH2:18][C:15]([CH2:20][C:21]([O:23][CH3:24])=[O:22])([CH2:16][CH2:17]2)[CH2:14][CH2:13][CH2:12]3)=[CH:7][CH:6]=1)=O.[NH2:27][C:28]1[C:29]([OH:35])=[N:30][CH:31]=[N:32][C:33]=1[NH2:34].Cl>CCO>[NH2:34][C:33]1[C:28]2[N:27]=[C:3]([C:5]3[CH:10]=[CH:9][C:8]([C:11]45[CH2:19][CH2:18][C:15]([CH2:20][C:21]([O:23][CH3:24])=[O:22])([CH2:16][CH2:17]4)[CH2:14][CH2:13][CH2:12]5)=[CH:7][CH:6]=3)[C:2]([CH3:26])([CH3:25])[O:35][C:29]=2[N:30]=[CH:31][N:32]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 25258351Methyl {5-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[3.2.2]non-1-yl}acetate2×HCID 178508814HCID 178508814, compound

Product 1

HCID 25258354methyl {5-[4-(4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl)phenyl]bicyclo[3.2.2]non-1-yl}acetateYield 65%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of methyl {5-[4-(2-bromo-2-methylpropanoyl)phenyl]bicyclo[3.2.2]non-1-yl}acetate (Intermediate 24; 80 mg, 0.19 mmol) in absolute EtOH (20 mL) was added 5,6-diaminopyrimidin-4-ol (30 mg, 0.21 mmol) followed by 1M HCl (0.21 mL). The suspension was heated under gentle reflux (80° C.) overnight then allowed to cool, the solvent removed and the residue treated with 2M NaOH (2 mL). The aqueous phase was extracted into EtOAc (3×50mL), the organic extracts were combined, dried (MgSO4) and concentrated to leave a pale yellow gum. This was purified on a 12 g Crawford silicycle cartridge, loading in DCM and eluting with 0-5-10% MeOH-DCM, giving the title compound as a pale yellow gum (55 mg, 0.123 mmol, 65%); 1H NMR (CDCl3) 1.41-1.61 (14H, m), 1.71 (6H, s), 2.07 (2H, s), 3.61 (3H, s), 7.11 (2H, d), 7.51 (2H, d), 8.14 (1H, s); MS m/e MH+ 449.

Workup

  1. temperatureThe suspension was heated
  2. temperatureto cool
  3. customthe solvent removed
  4. additionthe residue treated with 2M NaOH (2 mL)
  5. extractionThe aqueous phase was extracted into EtOAc (3×50mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customto leave a pale yellow gum
  9. customThis was purified on a 12 g Crawford silicycle cartridge, loading in DCM
  10. washeluting with 0-5-10% MeOH-DCM

Sources & evidence

ORD record
ord-5248102baae0449e8b44ad002676299c
Source dataset
uspto-grants-2010_07
Patent number
US07749997B2

Reaction notes

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