Water → 2-[3-(3-chlorophenyl)-7-((S)-2-methyl-3-pyrrolidin-1-ylpropoxy)-1-oxo-1H-isoquinolin-2-yl]-N-isopropylacetamide

Participants

Reaction Steps

To a stirred suspension of methanesulfonic acid (R)-3-[3-(3-chlorophenyl)-2-(isopropylcarbamoylmethyl)-1-oxo-1,2-dihydroisoquinolin-7-yloxy]-2-methylpropyl ester (310 mg, 0.595 mmol) in dry acetonitrile (3 mL) was added K2CO3 (412 mg, 2.98 mmol) and pyrrolidine (150 mL, 1.78 mmol). The mixture was heated at reflux temperature for 6 h and water (10 mL) was added. The resultant suspension was extracted with ethyl acetate (3×25 mL), and the combined organic extracts were dried (MgSO4) and concentrated in vacuo. Purification by chromatography on silica gel with MeOH:DCM:NH4OH (aq.) (1:18.9:0.1 v/v) gave 2-[3-(3-chlorophenyl)-7-((S)-2-methyl-3-pyrrolidin-1-ylpropoxy)-1-oxo-1H-isoquinolin-2-yl]-N-isopropylacetamide (EXAMPLE 1) (146 mg, 0.294 mmol, 67%). Data for 2-[3-(3-chlorophenyl)-7-((S)-2-methyl-3-pyrrolidin-1-ylpropoxy)-1-oxo-1H-isoquinolin-2-yl]-N-isopropylacetamide (EXAMPLE 1): 1H NMR (300 MHz, CDCl3): δ 7.83 (d, 1H), 7.47-7.37 (m, 5H), 7.30 (dd, 1H), 6.46 (s, 1H), 5.91 (br d, 1H), 4.45 (s, 2H), 4.15 (dd, 1H), 4.07 (septet, 1H), 3.91 (dd, 1H), 2.62-2.46 (br m, 5H), 2.36 (dd, 1H), 2.21 (dd, 1H), 1.80-1.76 (br m, 4H), 1.16 (d, 6H), 1.11 (d, 3H) ppm; MS (ESI) m/z: 496 ([M+H]+), 991 ([2M+H]+), 1013 ([2M+Na]+).

Provenance & Evidence