Sodium Hydroxide → {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}acetic Acid

HRID 908120Notes

Reaction equation

HRID 908120 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[CH2:26][CH2:25][C:22]([CH2:27][C:28]([O:30]C)=[O:29])([CH2:23][CH2:24]4)[CH2:21][CH2:20][CH2:19]5)=[CH:14][CH:13]=3)[C:8]([CH3:33])([CH3:32])[O:7][C:6]=2[N:5]=[CH:4][N:3]=1.[OH-].[Na+]>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[CH2:26][CH2:25][C:22]([CH2:27][C:28]([OH:30])=[O:29])([CH2:23][CH2:24]4)[CH2:21][CH2:20][CH2:19]5)=[CH:16][CH:17]=3)[C:8]([CH3:33])([CH3:32])[O:7][C:6]=2[N:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 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}acetate2×

Product 1

HCID 25016425{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}acetic AcidYield 59.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 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 (Intermediate 25; 55 mg, 0.12 mmol) in MeOH (5 mL) was added 2M NaOH (0.3 mL) and the reaction mixture was allowed to stir at ambient temperature overnight, then at 50° C. for 8 hrs and ambient temperature overnight. The solvent was removed under reduced pressure and the residue was acidified to pH 2 with 2M HCl, the filtrate extracted into EtOAc (2×50 mL), the organic extracts combined, dried (MgSO4) and concentrated to leave a yellow gum. The product was purified by reverse phase preparative HPLC, loading the sample in DMSO/MeCN/H2O (7:2:1) and eluting with 5-95 water-MeCN with 0.2% TFA in each phase, to provide the title compound (31 mg, 0.0714 mmol, 59%) as a pale yellow solid, 1H NMR δ 1.34-1.56 (14H, m), 1.63 (6H, s), 1.95 (2H, s), 7.15 (2H, d), 7.63-7.66 (2H, m), 8.02 (1H, s); MS m/e MH+ 435

Workup

  1. waitat 50° C. for 8 hrs
  2. customambient temperature overnight
  3. customThe solvent was removed under reduced pressure
  4. extractionthe filtrate extracted into EtOAc (2×50 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customto leave a yellow gum
  8. customThe product was purified by reverse phase preparative HPLC
  9. washeluting with 5-95 water-MeCN with 0.2% TFA in each phase

Sources & evidence

ORD record
ord-dd34bf30087b406e8bab9dfdc64fbd42
Source dataset
uspto-grants-2011_09
Patent number
US08017603B2

Reaction notes

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