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

HRID 467613Notes

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.ClCCl.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 mmol) 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 dichloromethane (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-f796e15947cf4bbba926ad523b51ce7a
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623866B2

Reaction notes

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