Acetic Anhydride → 2-[7-(Acetamidomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-3-isoquinolyl]-2-tert-butoxy-acetic acid

Participants

Reaction Steps

An ice cold solution of methyl 2-(7-(aminomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)-2-(tert-butoxy)acetate (25 mg, 0.057 mmol) in dichloromethane (DCM) (549 μl) was treated with Et3N (15.96 μl, 0.115 mmol) and acetic anhydride (8.11 μl, 0.086 mmol), and then stirred for 3 hours. The mixture was quenched with sat. NaHCO3, extracted with DCM, washed with brine, dried with Na2SO4, filtered, and concentrated. The residue was hydrolyzed in a manner similar to that described in Example 165 Step C and purified by reverse phase HPLC to afford 2-(7-(acetamidomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)-2-(tert-butoxy)acetic acid (21.6 mg, 0.045 mmol, 85% yield) as an off-white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm, 8.37 (s, 1 H), 7.47 (t, J=7.3 Hz, 1 H), 7.39-7.29 (m, 1 H), 7.24 (d, J=7.2 Hz, 1 H), 7.13 (dd, J=8.4, 12.6 Hz, 1 H), 7.09-6.98 (m, 1 H), 6.11 (br. s., 1 H), 5.34 (s, 1 H), 4.63-4.45 (m, 2 H), 3.69 (s, 3 H), 2.36 (s, 3 H), 2.31 (s, 3 H), 2.05 (s, 3 H), 1.10-0.96 (m, 9 H); LCMS (m/z) ES+=465 (M+1).

Provenance & Evidence