Sodium hydride → (E)-methyl 3-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)acrylate

Temperature

0 °C

A solution of trimethyl phosphonoacetate (0.225 g 1.00 mmol) in THF (20 mL) was added 95% sodium hydride (0.050 g, 2.0 mmol). Upon the completion of addition, the mixture was stirred at 0° C. for 30 min and then 5-phenyl-4-(pyridin-2-ylmethylamino)quinazoline-2-carbaldehyde (Example 212, prepared in a similar manner to the procedure described below, 0.340 g, 1.00 mmol) was added to the reaction mixture. The resulting mixture was stirred at room temperature for 14 h. After this time, the reaction mixture was quenched with saturated aqueous ammonium chloride solution (50 mL) and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The filtrate was concentrated and the resulting residue was subjected to silica gel column chromatography using 5% MeOH in chloroform as the eluent to provide (E)-methyl 3-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)acrylate (0.30 g, 72%) as a brown solid. LCMS Method V: retention time 1.94 min; [M+1]=411.2.

1. additionUpon the completion of addition
2. additionwas added to the reaction mixture
3. stirringThe resulting mixture was stirred at room temperature for 14 h
4. customAfter this time, the reaction mixture was quenched with saturated aqueous ammonium chloride solution (50 mL)
5. extractionextracted with ethyl acetate
6. washThe organic layer was washed with saturated brine
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltrated
9. concentrationThe filtrate was concentrated

ORD record

ord-90df72b2906e43998fd75a594eca65b0

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08575184B2