Sodium Hydroxide → (4-(4-(4-Amino-7,7-dimethyl-7H-pyrimido(4,5-b)(1,4)oxazin-6-yl)phenyl)bicyclo(2.2.2)oct-1-yl)acetic Acid

HRID 2353063Notes

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]([CH2:26][C:27]([O:29]C)=[O:28])([CH2:22][CH2:23]4)[CH2:20][CH2:19]5)=[CH:14][CH:13]=3)[C:8]([CH3:32])([CH3:31])[O:7][C:6]=2[N:5]=[CH:4][N:3]=1.[OH-].[Na+]>CO.C1COCC1>[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]([CH2:26][C:27]([OH:29])=[O:28])([CH2:20][CH2:19]4)[CH2:24][CH2:25]5)=[CH:16][CH:17]=3)[C:8]([CH3:32])([CH3:31])[O:7][C:6]=2[N:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 60 °C

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]oct-1-yl}acetate (Intermediate 10; 601 mg, 1.38 mmol) in MeOH (40 mL) and THF (40 mL) was added 2M NaOH solution (3.5 mL, 6.9 mmol). The reaction mixture was stirred at 60° C. overnight, the organic solvent was concentrated and the residue acidified with 2M HCl to pH 2. The suspension was filtered and the solid purified by reverse phase chromatography loading in DMSO/MeCN/H2O (7:2:1) with a few drops of concentrated ammonia solution and eluting 5-95% water (+0.5% NH3)-MeCN. The title compound was isolated as a white solid (302 mg, 0.717 mmol, 52%.

Workup

concentrationthe organic solvent was concentrated
filtrationThe suspension was filtered
customthe solid purified by reverse phase chromatography loading in DMSO/MeCN/H2O (7:2:1) with a few drops of concentrated ammonia solution
washeluting 5-95% water (+0.5% NH3)-MeCN

Sources & evidence

ORD record: ord-c94a4953f2a8486b88b78fd90bc91e47
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07749997B2

Reaction notes

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