Ethyl isocyanate → Methyl 2-(tert-butoxy)-2-(4-(3,4-dimethylphenyl)-7-((3-ethylureido)methyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)acetate

Participants

Reaction Conditions

Reaction Steps

A solution of methyl 2-(7-(aminomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)-2-(tert-butoxy)acetate (17 mg, 0.039 mmol) in Toluene (750 μl) was treated with ethyl isocyanate (9.25 μl, 0.117 mmol) and stirred at 70° C. for 2 hours. The reaction was cooled to rt, concentrated, and purified with column chromatography (0-10% MeOH/DCM) to afford methyl 2-(tert-butoxy)-2-(4-(3,4-dimethylphenyl)-7-((3-ethylureido)methyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)acetate (11.8 mg, 0.023 mmol, 59.7% yield). The methyl ester was then hydrolyzed in a manner similar to that described in Example 165 Step C and purified by reverse phase HPLC to afford 2-(tert-butoxy)-2-(4-(3,4-dimethylphenyl)-7-((3-ethylureido)methyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)acetic acid (9.1 mg, 0.018 mmol, 86% yield) as a white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.35 (s, 1 H), 7.56-7.42 (m, 1 H), 7.37-7.28 (m, 1 H), 7.25-7.20 (m, 1 H), 7.12 (dd, J=8.5, 11.0 Hz, 1 H), 7.08-6.97 (m, 1 H), 5.32 (d, J=3.1 Hz, 1 H), 4.46 (s, 2 H), 3.69 (s, 3 H), 3.18 (q, J=7.1 Hz, 2 H), 2.36 (s, 3 H), 2.30 (d, J=9.4 Hz, 3 H), 1.13 (t, J=7.2 Hz, 3 H), 1.04 (d, J=5.1 Hz, 9 H); LCMS (m/z) ES+=494 (M+1).

Provenance & Evidence