Ammonium Hydroxide → 5-Amino-2-(2,6-difluorophenyl)pyrimidine-4-carboxylic acid

HRID 879143Notes

Reaction equation

Br[C:2]1[C:3]([C:16]([OH:18])=[O:17])=[N:4][C:5]([C:8]2[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:9]=2[F:15])=[N:6][CH:7]=1.[OH-].[NH4+:20]>C(=O)=O.[O-]S([O-])(=O)=O.[Cu+2]>[NH2:20][C:2]1[C:3]([C:16]([OH:18])=[O:17])=[N:4][C:5]([C:8]2[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:9]=2[F:15])=[N:6][CH:7]=1

Participants

Conditions

Temperature: 110 °C

Procedure

CuSO4 (0.1 eq) was added to a mixture of 5-bromo-2-(2,6-difluorophenyl)pyrimidine-4-carboxylic acid (1 eq) and 28% aqueous ammonium hydroxide solution in a microwave reaction vessel. The reaction mixture was heated in a microwave reactor at 110° C. for 25 min. The reaction vessel was cooled in dry ice for 30 min then unsealed and concentrated in vacuo. To the resulting solids was added 1.0 N HCl and the mixture was extracted with EtOAc. Combined organic extracts were washed once with brine, then dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 5-amino-2-(2,6-difluorophenyl)pyrimidine-4-carboxylic acid. The crude product was used for the next step without further purification. LCMS (m/z): 252.0 (MH+), Rt=2.0 min.

Workup

concentrationunsealed and concentrated in vacuo
additionTo the resulting solids was added 1.0 N HCl
extractionthe mixture was extracted with EtOAc
washCombined organic extracts were washed once with brine
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-9b6b3b128dd24588b93ce8280444ff20
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987457B2

Reaction notes

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