Acetic Acid → 2(3H)-Benzoxazolone, 5-[[2-[(4-fluoro-3-methoxy-5-methylphenyl)amino]-5-methyl-4-pyrimidinyl]amino]-3-[(phosphonooxy)methyl]-

HRID 2178182Notes

Reaction equation

[P:1]([O:13][CH2:14][N:15]1[C:19]2[CH:20]=[C:21]([NH:24][C:25]3[C:30]([CH3:31])=[CH:29][N:28]=[C:27]([NH:32][C:33]4[CH:38]=[C:37]([CH3:39])[C:36]([F:40])=[C:35]([O:41][CH3:42])[CH:34]=4)[N:26]=3)[CH:22]=[CH:23][C:18]=2[O:17][C:16]1=[O:43])([O:8]C(C)(C)C)([O:3]C(C)(C)C)=[O:2].CC(O)=O>O>[P:1]([OH:8])([OH:3])([O:13][CH2:14][N:15]1[C:19]2[CH:20]=[C:21]([NH:24][C:25]3[C:30]([CH3:31])=[CH:29][N:28]=[C:27]([NH:32][C:33]4[CH:38]=[C:37]([CH3:39])[C:36]([F:40])=[C:35]([O:41][CH3:42])[CH:34]=4)[N:26]=3)[CH:22]=[CH:23][C:18]=2[O:17][C:16]1=[O:43])=[O:2]

Participants

Conditions

Temperature: 65 °C

Procedure

To the crude di-tert-butyl (5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)-2-oxobenzo[d]oxazol-3(2H)-yl)methyl phosphate, was added HOAc (280 mL) and H2O (70 mL), the resultant light brown homogeneous solution was stirred at 65° C. (note: a lighter color ppt was formed between 15-45 min). The reaction was monitored by LC-MS. After 1 h, the mixture was cooled to rt, ppt was collected by filtration, washing with H2O (˜50 mL×2). Product (5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)-2-oxobenzo[d]oxazol-3(2H)-yl)methyl dihydrogen phosphate was obtained as a light pinkish beige color solid and was used directly in salt formation.

Workup

customa lighter color ppt was formed between 15-45 min)
temperaturethe mixture was cooled to rt
filtrationppt was collected by filtration
washwashing with H2O (˜50 mL×2)

Sources & evidence

ORD record: ord-6b5b7fe7cb014ad4bb05a183ff95affb
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067925B2

Reaction notes

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