4-Chloro-2-fluoro-3-methoxyphenylboronic acid → 6-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)pyrimidine-4-carboxylic acid methyl ester

HRID 1593975Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[CH:10]=[C:9]([NH2:11])[N:8]=[C:7](Cl)[N:6]=1)=[O:4].[Cl:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[C:16]([F:23])[C:15]=1[O:24][CH3:25]>C(COC)OC.O>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[C:9]([NH2:11])[N:8]=[C:7]([C:17]2[CH:18]=[CH:19][C:14]([Cl:13])=[C:15]([O:24][CH3:25])[C:16]=2[F:23])[N:6]=1)=[O:4]

Participants

Conditions

Temperature: 80 °C

Procedure

6-Amino-2-chloro-pyrimidine-4-carboxylic acid methyl ester (2.25 g, 12 mmol), 4-chloro-2-fluoro-3-methoxyphenylboronic acid (3.27 g, 16 mmol), and bis(triphenylphosphine)palladium(II) dichoride (842 mg, 1.2 mmol) were combined in 12 mL of dimethoxyethane and 12 mL of water. The reaction mixture was heated at 80° C. for 2 hours and the cooled reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water, dried, and concentrated under vacuum. The product was purified by column chromatography to yield 6-amino-2-(4-chloro-2-fluoro-3-methoxy-phenyl)pyrimidine-4-carboxylic acid methyl ester (2.0 g, 53.5% yield): mp 188-190° C.: 1H NMR (CDCl3): δ 7.66 (dd, 1H), 7.22 (dd, 1H), 7.14 (s, 1H), 5.25 (br s, 2H), 4.0 (s, 3H), 3.99 (s, 3H).

Workup

customthe cooled reaction mixture
customwas partitioned between ethyl acetate and water
washThe organic phase was washed with water
customdried
concentrationconcentrated under vacuum
customThe product was purified by column chromatography

Sources & evidence

ORD record: ord-9a97844273c942029ca7f93e16809f8a
Source dataset: uspto-grants-2007_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07300907B2

Reaction notes

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