Water → 2-Pyridinecarboxylic acid, 6-chloro-3-(5-pyrimidinylamino)-, ethyl ester

HRID 467747Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[C:11]([NH2:12])=[CH:10][CH:9]=[C:8]([Cl: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+].O.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>CC1C=CC=CC=1C.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=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)=[CH:10][CH:9]=[C:8]([Cl:13])[N:7]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 140 °C

Procedure

A suspension of 3-amino-6-chloro-pyridine-2-carboxylic acid ethyl ester (200 mg, 1.0 mmol), 5-bromopyrimidine (444 mg, 2.8 mmol), potassium carbonate (496 mg, 3.6 mmol) and water (76 μl, 4.4 mmol) in o-xylene was evacuated and vented with argon. Palladium(II) acetate (27 mg, 0.12 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos; 87 mg, 0.15 mmol) were added under argon and the reaction mixture was stirred at 140° C. for 60 h. After cooling down to ambient temperature, the reaction mixture was diluted with dichloromethane and the product was obtained after purification by silica gel chromatography using a heptane/ethyl acetate gradient as light yellow solid (98 mg, 35%).

Workup

customwas evacuated
temperatureAfter cooling down to ambient temperature
customthe product was obtained
customafter purification by silica gel chromatography

Sources & evidence

ORD record: ord-b5d1ba35b4244dc18469ff0f31a1befd
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623866B2

Reaction notes

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