Tributylstannane → HCID 59432118, compound

HRID 245301Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C:10]([CH:11]([F:14])[CH2:12]Br)=[C:9]([NH2:15])[N:8]=[C:7]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH3:24])[C:17]=2[F:25])[N:6]=1)=[O:4].C([SnH](CCCC)CCCC)CCC>COCCOC.N(C(C)(C)C#N)=NC(C)(C)C#N>[CH3:1][O:2][C:3]([C:5]1[C:10]([CH:11]([F:14])[CH3:12])=[C:9]([NH2:15])[N:8]=[C:7]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH3:24])[C:17]=2[F:25])[N:6]=1)=[O:4]

Participants

Conditions

Temperature: 100 °C

Procedure

6-Amino-5-(2-bromo-1-fluoroethyl)-2-(4-chloro-2-fluoro-3-methoxyphenyl)pyrimidine-4-carboxylic acid methyl ester (324 mg, 0.742 mmol), tri-n-butyltin hydride (0.396 mL, 1.484 mmol), and 2,2′-azobisisobutyronitrile (3.05 mg, 0.019 mmol) were combined in 1,2-dimethoxyethane (2.5 mL) and heated at 100° C. for 15 min in a CEM microwave reactor. 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 (162 mg, 61.0% yield) as a white solid, mp 150-152° C.: 1H NMR (CDCl3) δ 7.64 (dd, 1H), 7.22 (dd, 1H), 6.26 (dq, 1H), 5.73 (br s, 2H), 4.00 (d, 3H), 3.98 (s, 3H), 1.80 (dd, 3H).

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-5afaae62a3f44e59bf0213aeb631b44d
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658791B2

Reaction notes

Loading…