Water → 6-Cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carboxylic acid ethyl ester

HRID 1260291Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[C:11]([NH2:12])=[CH:10][CH:9]=[C:8]([CH:13]2[CH2:15][CH2:14]2)[N:7]=1)=[O:5])[CH3:2].Br[C:17]1[CH:18]=[N:19][CH:20]=[N:21][CH:22]=1.O.C(=O)([O-])[O-].[K+].[K+]>CC1C=CC=CC=1C.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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>[CH2:1]([O:3][C:4]([C:6]1[C:11]([NH:12][C:17]2[CH:18]=[N:19][CH:20]=[N:21][CH:22]=2)=[CH:10][CH:9]=[C:8]([CH:13]2[CH2:14][CH2:15]2)[N:7]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 140 °C

Procedure

A suspension of 3-amino-6-cyclopropylpyridine-2-carboxylic acid ethyl ester (763 mg, 3.7 mmol), 5-bromopyrimidine (823 mg, 5.2 mmol), water (140 μl, 7.8 mmol) and potassium carbonate (920 mg, 6.7 mmol) in o-xylene (10 ml) was evacuated and vented with argon. Palladium(II) acetate (33 mg, 0.15 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos; 107 mg, 0.18 μmol) were consecutively added under inert gas atmosphere and the reaction mixture was heated to 140° C. and stirred overnight. After cooling-down to ambient temperature, the reaction mixture was diluted with methylenechloride (15 ml) and filtrated. The filtrate was concentrated in vacuo and the product was purified by silica gel chromatography using a heptane/ethyl acetate gradient to yield the title compound (796 mg, 75.7%) as light yellow solid.

Workup

customwas evacuated
filtrationfiltrated
concentrationThe filtrate was concentrated in vacuo
customthe product was purified by silica gel chromatography

Sources & evidence

ORD record: ord-b629870ccfb3475f9bde41e4e4cb91a8
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08470820B2

Reaction notes

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