Ethanol → 4-(4-{4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl}phenyl)bicyclo[2.2.2]octane-1-carboxylic acid

HRID 908124Notes

Reaction equation

HRID 908124 reaction equation
[NH2:1][C:2]1[C:11]2[N:10]=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([C:18]45[CH2:25][CH2:24][C:21]([C:26]([O:28]C)=[O:27])([CH2:22][CH2:23]4)[CH2:20][CH2:19]5)=[CH:14][CH:13]=3)[C:8]([CH3:31])([CH3:30])[O:7][C:6]=2[N:5]=[CH:4][N:3]=1.[OH-].[Na+].CCO>CO>[NH2:1][C:2]1[C:11]2[N:10]=[C:9]([C:12]3[CH:13]=[CH:14][C:15]([C:18]45[CH2:23][CH2:22][C:21]([C:26]([OH:28])=[O:27])([CH2:20][CH2:19]4)[CH2:24][CH2:25]5)=[CH:16][CH:17]=3)[C:8]([CH3:31])([CH3:30])[O:7][C:6]=2[N:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 14798Sodium Hydroxide2×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-carboxylate2×

Product 1

HCID 250164264-(4-{4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl}phenyl)bicyclo[2.2.2]octane-1-carboxylic acidYield 724.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 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 (Intermediate 27; 140 mg, 0.33 mmol) in MeOH (10 mL) was added 2M NaOH (0.82 mL, 1.66 mmol). The reaction mixture was allowed to stir at ambient temperature overnight and then after the addition of EtOH (˜5 mL) and 1M NaOH (2 mL) the reaction mixture was heated to 50° C. for 5.5 hrs. The organic solvent was removed by evaporation under reduced pressure and the residue was acidified to pH 2 with 2M HCl. EtOAc was added and the suspension was filtered and dried to provide the title compound (97 mg, 2.39 mmol, 72%); 1H NMR δ 1.60 (s, 6H), 1.82 (s, 12H), 6.97 (s, 1H), 7.40 (d, 2H), 7.65 (d, 2H), 7.95 (s, 1H), NH2 not seen; MS m/e MH+ 407.

Workup

  1. temperaturewas heated to 50° C. for 5.5 hrs
  2. customThe organic solvent was removed by evaporation under reduced pressure
  3. additionEtOAc was added
  4. filtrationthe suspension was filtered
  5. customdried

Sources & evidence

ORD record
ord-741dfe5e71174cd5a48833074dae8505
Source dataset
uspto-grants-2011_09
Patent number
US08017603B2

Reaction notes

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