Potassium Carbonate → 6-Methyl-3-(pyrimidin-5-ylamino)-pyrazine-2-carboxylic acid ethyl ester

HRID 1260303Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[C:11]([NH2:12])=[N:10][CH:9]=[C:8]([CH3:13])[N:7]=1)=[O:5])[CH3:2].Br[C:15]1[CH:16]=[N:17][CH:18]=[N:19][CH:20]=1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1(C)C(C)=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCCCCCC.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:11]([NH:12][C:15]2[CH:16]=[N:17][CH:18]=[N:19][CH:20]=2)=[N:10][CH:9]=[C:8]([CH3:13])[N:7]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 140 °C

Procedure

A suspension of 3-amino-6-methyl-pyrazine-2-carboxylic acid ethyl ester (500 mg, 2.8 mmol), 5-bromopyrimidine (614 mg, 3.9 mmol), water (104 μl, 5.8 mmol) and potassium carbonate (686 mg, 5.0 mmol) in xylene (7 ml) was vented with argon. Palladium(II) acetate (25 mg, 0.11 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos; 80 mg, 0.14 mmol) were consecutively added under inert gas atmosphere and the reaction mixture was heated to 140° C. and stirred for 5 h. After cooling-down to ambient temperature, the reaction mixture was diluted with water (5 ml) and extracted with methylenechloride. The organic layers were washed with water and brine, dried and concentrated in vacuo. The product was obtained after silica gel chromatography using a heptane/ethyl acetate gradient as light yellow solid (585 mg, 81.8%). MS: M=260.1 (M+H)+

Workup

extractionextracted with methylenechloride
washThe organic layers were washed with water and brine
customdried
concentrationconcentrated in vacuo
customThe product was obtained after silica gel chromatography

Sources & evidence

ORD record: ord-06d7d6d1939a4efa9d80e366134af380
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08470820B2

Reaction notes

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