Dimethylformamide → (R)-2-(5-((S)-2-(4-Chlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-N,3-dimethylbutanamide

Participants

Reaction Steps

(R)-2-(5-Amino-1-oxoisoquinolin-2(1H)-yl)-N,3-dimethylbutanamide (0.2 g, 0.0007 mol), (S)-2-(4-chlorophenyl)propanoic acid (0.16 g, 0.00088 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.56 g, 0.0015 mol), N,N-diisopropylethylamine (0.4 g, 0.003 mol) were stirred in methylene chloride (3 mL, 0.05 mol) and N,N-dimethylformamide (1 mL, 0.01 mol) at room temperature over a weekend. The reaction mixture was diluted with CH2Cl2 (100 mL), washed with NaHCO3 (20 mL×3), dried over Na2SO4, purified via flash chromatography (12 g of silica gel, 0-90% EtOAc/Hexane), and then prep. HPLC yielded a white solid. 1H NMRδ (CDCl3) δ: 9.23 (d, J=8.1 Hz, 1H), 8.00 (t, J=7.5 Hz, 1H), 7.52-7.36 (m, 6H), 7.04 (br, 1H), 6.17 (br, 1H), 6.03-6.00 (m, 1H), 5.07 (d, J=11.4 Hz, 1H), 3.82 (q, J=7.0 Hz, 1H), 2.76 (d, J=4.8 Hz, 3H), 2.56-2.48 (m, 1H), 1.65 (dd, J=1.8, 7.1 Hz, 3H), 1.06 (d, J=6.4 Hz, 3H), 0.75 (dd, J=2.6, 6.6 Hz, 3H). MS m/z 440.0 (M+H)+.

Provenance & Evidence