Ammonia → Methyl [7-(aminomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate

Participants

Reaction Steps

A solution of methyl [7-cyano-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate (30 mg, 0.069 mmol) in Ethanol (3.5 mL), saturated with ammonia gas, was treated with Raney 2800 Nickel (0.5 mL, 0.069 mmol), purged and filled with N2 3×, H2 3×, and stirred under H2 at 40 psi overnight. The mixture was filtered through Celite, washed with MeOH, and concentrated. The residue was purified by column chromatography (0-20% MeOH/DCM) to afford methyl [7-(aminomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate (23.7 mg, 0.054 mmol, 78% yield) as a colorless oil. The methyl ester was hydrolyzed in a manner similar to that described in Example 165 Step C and purified by reverse phase HPLC to afford [7-(aminomethyl)-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetic acid-TFA salt (18.8 mg, 0.033 mmol, 76% yield) as off white solid: 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.42 (s, 1 H), 7.61 (d, J=8.4 Hz, 1 H), 7.36-7.15 (m, 3 H), 7.11-6.99 (m, 1 H), 5.23 (s, 1 H), 4.23 (s, 2 H), 3.70 (s, 3 H), 2.36 (s, 3 H), 2.31 (s, 3 H), 0.98 (s, 9 H); LCMS (m/z) ES+=423 (M+1).

Provenance & Evidence