Acetaldehyde → HCID 86594621, compound

Participants

Reaction Steps

To a solution of 3-[5-(4-amino-3-trifluoromethylphenyl)thiophen-2-yl]-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one (28 mg, 51 μmol) in toluene (1 mL) was added one drop of acetic acid, and a molar excess of acetaldehyde. The mixture was stirred for 20 minutes at ambient temperature and then concentrated under reduced pressure. The residue was taken up in 25% HOAc/MeOH (1 mL), and a molar excess of NaCNBH3 was added. After stirring for 16 hours at ambient temperature there was still starting material present. Additional acetaldehyde was added. After 30 minutes a yellow solid appeared in the reaction. This solid was collected by filtration and was purified by silica gel column chromatography eluting with a gradient from 0% to 20% ethyl acetate/hexane on silica. The product peak was collected to afford 8-chloro-2-(2,4-difluorobenzyl)-3-[5-(4-ethylamino-3-trifluoromethylphenyl)thiophen-2-yl]-2H-isoquinolin-1-one (10 mg, 34% yield) as a yellow solid. 1H-NMR (400 MHz, CDCl3): δ 7.62-7.60 (1H, m), 7.55-7.51 (3H, m), 7.44-7.40 (1H, m), 7.05-6.98 (2H, m), 6.85 (1H, d, J=3.8 Hz), 6.82-6.72 (3H, m), 6.67 (1H, s), 5.36 (2H, s), 4.40 (1H, s), 3.29-3.22 (2H, m), 1.32 (3H, t, J=7.1 Hz) ppm.

Provenance & Evidence