Toluene → 4-[3-(2-Chloro-3-fluoro-benzyl)-1-methyl-ureido]-5-(isoquinolin-3-ylcarbamoyloxy)-pentanoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-(tert-Butyl-dimethyl-silanyloxy)-4-[3-(2-chloro-3-fluoro-benzyl)-1-methyl-ureido]-pentanoic acid methyl ester (21.0 g, 45.6 mmol) in THF (450 mL) was slowly added TBAF (1 M in THF, 68.4 mL, 68.4 mmol). The reaction was stirred at 24° C. for 1 h. THF was removed. The residue was diluted with EtOAc (600 mL) and washed with saturated aq. NH4Cl and brine. The organic layers were dried over Na2SO4 and concentrated. The resulting residue was dissolved in toluene and added into a toluene solution of isoquinoline-3-carbonyl azide (9.07 g, 45.6 mmol) at 100° C. The reaction mixture was heated to 100° C. for 1 h and then concentrated. Resulting residue was purified on silica gel column using hexanes and EtOAc to give 4-[3-(2-chloro-3-fluoro-benzyl)-1-methyl-ureido]-5-(isoquinolin-3-ylcarbamoyloxy)-pentanoic acid methyl ester (16.8 g, 71%) as a colorless oil. LRMS (M+H+) m/z 517.1.

Provenance & Evidence