Reaction #46535

Reaction equation

6-bromo-3,4-dihydro-1H-1,8-naphthyridin-2-one

tert-butyl acrylate

DIEA

P(o-tol)3

→

title compound

Yield 45.3%

tert-Butyl (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylate

Yield 45.3%

Solvents

propionitrile

DMF

Conditions

Workup

1. 1
   Temperaturewas heated
2. 2
   Temperatureat reflux
3. 3
   Concentrationwas concentrated to dryness
4. 4
   OtherThe residue was purified by flash chromatography on silica gel (2-4% MeOH/CHCl3)
5. 5
   OtherThe resulting residue was triturated with 1:1 Et2O/petroleum ether
6. 6
   Othercollected
7. 7
   Otherdried
8. 8
   Otherthe resulting material was triturated with 1:1 MeOH/H2O
9. 9
   Othercollected
10. 10
    Otherdried

Procedure

A solution of 6-bromo-3,4-dihydro-1H-1,8-naphthyridin-2-one (12.99 g, 57 mmole), tert-butyl acrylate (34 mL, 232 mmole), DIEA (21.2 mL, 122 mmole), Pd(OAc)2 (1.3 g, 5.8 mmole) and P(o-tol)3 (3.5 g, 11.5 mmole) in propionitrile (200 mL) and DMF (50 mL) was purged with Ar, then was heated at reflux. After 18 h the reaction was allowed to cool to room temperature and was concentrated to dryness. The residue was purified by flash chromatography on silica gel (2-4% MeOH/CHCl3). The resulting residue was triturated with 1:1 Et2O/petroleum ether, collected, and dried, and the resulting material was triturated with 1:1 MeOH/H2O, collected, and dried, to give the title compound (7.09 g, 45%) as an off-white solid: 1H NMR (400 MHz, d6-DMSO) δ 10.70 (s, 1 H), 8.35 (d, J=2.0 Hz, 1H), 8.04 (s, 1 H), 7.50 (d, J=16.0 Hz, 1 H), 6.51 (d, J=16.0 Hz, 1 H), 2.89 (t, 2H), 2.53 (t, 2 H), 1.48 (s, 9H); MS (ES) m/e 275.2 (M+H)+.

Source