Formaldehyde → 7-[(2-hydroxyethyl)methylamino]-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one

120 mg (1.0 mmol) of glycolaldehyde dimer and 2 ml of acetic acid were added to 10 ml of a methanol solution containing 473 mg (1.55 mmol) of the 7-amino-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one obtained in Example 38. Thereafter, 754 mg (12.0 mmol) of sodium cyanoborohydride was further added thereto, and the obtained mixture was then stirred at a room temperature for 3 hours. Thereafter, 0.82 ml (10 mmol) of a 37% formalin aqueous solution was added to the reaction solution, and the obtained mixture was further stirred for 2.5 hours. Thereafter, the reaction solution was concentrated, and a saturated sodium bicarbonate aqueous solution and methylene chloride were then added to the concentrate. An organic layer was separated, and was then dried over anhydrous sodium sulfate. Thereafter, the solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel chromatography (hexane:ethyl acetate methanol=15:30:1), so as to obtain 344 mg (61%) of 7-[(2-hydroxyethyl)methylamino]-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one in the form of a yellow solid.

1. stirringthe obtained mixture was further stirred for 2.5 hours
2. concentrationThereafter, the reaction solution was concentrated
3. additiona saturated sodium bicarbonate aqueous solution and methylene chloride were then added to the concentrate
4. customAn organic layer was separated
5. dry with materialwas then dried over anhydrous sodium sulfate
6. distillationThereafter, the solvent was distilled away under reduced pressure
7. customThe obtained residue was purified by silica gel chromatography (hexane:ethyl acetate methanol=15:30:1)

ORD record

ord-28e1e3827a8e4c2aafb79d641d2f5a11

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08143274B2