Trimethyl((tributylstannyl)ethynyl)silane → 6-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-trimethylsilanylethynylpyrimidine-4-carboxylic acid methyl ester

HRID 245288Notes

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].[CH3:23][Si:24]([CH3:41])([CH3:40])[C:25]#[C:26][Sn](CCCC)(CCCC)CCCC>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]([C:26]#[C:25][Si:24]([CH3:41])([CH3:40])[CH3:23])=[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: 110 °C

Procedure

6-Amino-5-bromo-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylic acid methyl ester (1.0 g, 2.56 mmol), trimethyl((tributylstannyl)ethynyl)silane (1.98 g, 5.12 mmol), and bis(triphenylphosphine)palladium(II) dichloride (0.18 g, 0.256 mmol) were combined in 1,2-dichloroethane (10 mL) and heated in a CEM microwave reactor at 110° C. for 15 min. The cooled reaction mixture was concentrated under vacuum then purified by flash chromatography on silica gel (dichloromethane/ethyl acetate gradient). A second purification by flash chromatography on silica gel (hexane/ethyl acetate gradient) yielded the title compound (0.829 g, 79% yield): mp 126-128° C.

Workup

customThe cooled reaction mixture
concentrationwas concentrated under vacuum
customthen purified by flash chromatography on silica gel (dichloromethane/ethyl acetate gradient)
customA second purification by flash chromatography on silica gel (hexane/ethyl acetate gradient)

Sources & evidence

ORD record: ord-e08f5a3451d74ce5b80bb15037781f8c
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658791B2

Reaction notes

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