Tributylvinyltin → 4-Amino-6-(4-chlorophenyl)-5-fluoro-3-vinylpyridine-2-carboxylic acid methyl ester

HRID 506466Notes

Reaction equation

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

Participants

Conditions

Temperature: 110 °C

Procedure

4-Amino-3-chloro-6-(4-chlorophenyl)-5-fluoropyridine-2-carboxylic acid methyl ester (0.5 g, 1.59 mmol), tributyl(vinyl)tin (1.01 g, 3.17 mmol), bis(triphenylphosphine)palladium(II) dichloride (0.111 g, 0.159 mmol), and tetrabutylammonium triphenyldifluorosilicate (1.71 g, 3.17 mmol) were combined in acetonitrile (3 ml) and heated to 110° 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 (hexane/ethyl acetate gradient) twice to yield the title compound (46 mg, 5% yield) as an off-white solid, mp 81-83° C. 1H NMR (CDCl3) δ 7.9 (m, 1H), 7.43 (m, 1H), 6.89 (dd, 1H), 5.7 (dd, 1H), 5.57 (dd, 1H), 4.72 (br s, 2H), 3.93 (s, 3H).

Workup

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

Sources & evidence

ORD record: ord-80995cb1d613432da73e659147cab1a9
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07786044B2

Reaction notes

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