Tributylvinyltin → 4-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-ethenyl-6-methoxycarbonylpyrimidine

HRID 245283Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C:10](Br)=[C:9]([NH2:12])[N:8]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([O:20][CH3:21])[C:14]=2[F:22])[N:6]=1)=[O:4].[CH2:23]([Sn](CCCC)(CCCC)C=C)[CH2:24]CC>ClCCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:10]([CH:23]=[CH2:24])=[C:9]([NH2:12])[N:8]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([O:20][CH3:21])[C:14]=2[F:22])[N:6]=1)=[O:4]

Participants

Conditions

Temperature: 130 °C

Procedure

6-Amino-5-bromo-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylic acid methyl ester (1.5 g, 3.84 mmol), tributyl(vinyl)tin (2.436 g, 7.68 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.270 g, 0.384 mmol) were combined in 1,2-dichloroethane (4 mL) and heated at 130° C. for 15 min in a CEM microwave reactor. The cooled reaction mixture was concentrated onto silica gel and purified by flash chromatography on silica gel (ethyl acetate/hexane gradient) to yield the title compound (1.06 g, 82% yield): mp 145-147° C.: 1H NMR (CDCl3) δ 7.64 (m, 1H), 7.22 (m, 1H), 6.84 (dd, 1H), 5.68 (m, 2H), 5.43 (br s, 2H), 3.99 (d, 3H), 3.95 (s, 3H).

Workup

customThe cooled reaction mixture
concentrationwas concentrated onto silica gel
custompurified by flash chromatography on silica gel (ethyl acetate/hexane gradient)

Sources & evidence

ORD record: ord-1fde6c3450ad4da49884da77e4ab00b3
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658791B2

Reaction notes

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