Dimethylformamide → (R)-2-(4-Chloro-phenyl)-N-[2-((R)-1-hydroxymethyl-3-methyl-butyl)-1-oxo-1,2-dihydro-isoquinolin-5-yl]-propionamide

Participants

Reaction Conditions

Reaction Steps

Into a 20 ml reaction vial reaction vial was combined (R)-2-(5-amino-1-oxoisoquinolin-2(1H)-yl)-4-methylpentyl acetate (0.23 g, 0.00076 mol), (R)-2-(4-chlorophenyl)propanoic acid (0.175 g, 0.000949 mol) N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.58 g, 0.0015 mol) N,N-diisopropylethylamine (0.26 mL, 0.0015 mol), and N,N-dimethylformamide (4 mL, 0.06 mol). The mixture was heated at 50° C. for 3 hours and allowed to cool to room temperature. The mixture was poured on to saturated sodium bicarbonate (200 ml) and extracted with ethyl acetate (3×100 ml). The combined extracts were dried over sodium sulfate and reduced in vacuo to yield a light brown oil. The oil was taken up in methanol (10 ml) and 2N NaOH (10 ml) was added. The mixture was allowed to stir overnight. The volatiles were removed and the mixture was extracted with methylene chloride (2×20 ml). The combined extracts were reduced in vacuo and the mixture was purified by reversed phase prep HPLC using an acetonitrile: water gradient at pH 10. The combined pure fractions were reduced in vacuo to yield the title compound as yellow solid.

Provenance & Evidence