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

tert-Butyl acrylate (1.25 mL, 8.53 mmol), diisopropylethylamine (730 μL, 4.26 mmol) and P(o-tolyl)3 (130 mg, 0.43 mmol) were successively added to a suspension of ethyl 2-(6-bromo-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)acetate (670 mg, 2.13 mmol) in propionitrile (11 mL) and dimethylformamide (2.5 mL). The resulting mixture was purged with argon prior to the addition of palladium acetate (48 mg, 0.213 mmol). The mixture was purged with argon a second time and refluxed overnight. The reaction mixture was then filtered on Celite® and washed with ethyl acetate (75 mL) and dichloromethane (75 mL). The filtrate was concentrated to dryness and the residue was partitioned between dichloromethane (50 mL) and water (50 mL). The aqueous phase was separated and extracted with dichloromethane (2×100 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was precipitated from a mixture dichloromethane/diethylether to afford the title product as a white solid (460 mg, 60%).

1. customThe resulting mixture was purged with argon
2. customThe mixture was purged with argon a second time
3. temperaturerefluxed overnight
4. filtrationThe reaction mixture was then filtered on Celite®
5. washwashed with ethyl acetate (75 mL) and dichloromethane (75 mL)
6. concentrationThe filtrate was concentrated to dryness
7. customthe residue was partitioned between dichloromethane (50 mL) and water (50 mL)
8. customThe aqueous phase was separated
9. extractionextracted with dichloromethane (2×100 mL)
10. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL)
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated to dryness
14. customThe residue was precipitated from a mixture dichloromethane/diethylether

ORD record

ord-6910960221124173bfcad19553657011

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321769B2