tert-Butyl acrylate → (E)-tert-Butyl 3-(3-(2-(4-methylpiperazin-1-yl)ethyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)acrylate

tert-Butyl acrylate (830 μL, 5.64 mmol), diisopropylethylamine (500 L, 2.82 mmol) and P(o-tolyl)3 (86 mg, 0.28 mmol) were successively added to a suspension of 6-bromo-3-(2-(4-methylpiperazin-1-yl)ethyl)-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one (500 mg, 1.41 mmol) in propionitrile (6 mL) and dimethylformamide (2 mL). The resulting mixture was purged with argon prior to the addition of palladium acetate (32 mg, 0.14 mmol). The mixture was then purged a second time with argon and refluxed overnight. The reaction mixture was filtered on Celite® and washed with ethyl acetate (100 mL) and dichloromethane (100 mL). The filtrate was concentrated to dryness and the residue was solubilized in dichloromethane (100 mL). The resulting solution was washed with a saturated solution of sodium chloride (3×100 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol/ammoniac (1:0:0.1 to 98:2:0.1) as eluent. The title product was obtained as a brown solid (83 mg, 15%).

1. customThe resulting mixture was purged with argon
2. customThe mixture was then purged a second time with argon
3. temperaturerefluxed overnight
4. filtrationThe reaction mixture was filtered on Celite®
5. washwashed with ethyl acetate (100 mL) and dichloromethane (100 mL)
6. concentrationThe filtrate was concentrated to dryness
7. washThe resulting solution was washed with a saturated solution of sodium chloride (3×100 mL)
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated to dryness
11. customThe residue was purified by chromatography on silica gel

ORDレコード

ord-3cdd976ca7064b38815938ec5e9c050f

出典データセット

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09051321B2