Hydrochloric Acid → 1-(2-[6-Methyl-8-[4-(1-phenyl-1H-pyrazol-3-ylmethyl)-[1,4]diazepan-1-yl]-quinolin-7-yloxy]-acetyl)-azetidine-3-carboxylic Acid

Participants

Reaction Steps

1-(2-{6-Methyl-8-[4-(1-phenyl-1H-pyrazol-3-ylmethyl)-[1,4]diazepan-1-yl]-quinolin-7-yloxy}-acetyl)-azetidine-3-carboxylic acid methyl ester (70 mg, 0.12 mmol) was hydrolyzed with 2 N NaOH (0.15 mL) in THF (1 ml). After hydrolysis was complete, 2 N HCl (ca. 0.15 mL) was added to bring the pH to 7 and the mixture was extracted with 20% iPrOH in CH2Cl2 (3×10 mL). The combined organic layer was dried over MgSO4 and concentrated. The residue was purified by reverse phase HPLC to afford the title compound (45 mg, 66%) as a light yellow solid. 1H NMR (400 MHz, DMSO) δ 8.75 (d, 1H, J=4.4 Hz), 8.42 (d, 1H, J=2.4 Hz), 8.14 (dd, 1H, J=1.6 and 8.4 Hz), 7.78 (d, 2H, J=8.0 Hz), 7.48-7.42 (m, 3H), 7.35 (q, 1H, J=4.4 Hz), 7.25 (t, 1H, J=7.2 Hz), 6.51 (d, 1H, J=2.8 Hz), 4.77 (s, 2H), 4.40 (t, 1H, J=10.0 Hz), 4.31 (t, 1H, J=6.4 Hz), 4.08 (t, 1H, J=9.2 Hz), 3.97-3.93 (m, 1H), 3.82 (s, 2H), 3.48-3.38 (m, 5H), 2.88 (s, 4H), 2.38 (s, 3H), 1.92 (m, 2H). MS (ES) m/z 555.5 (M+H+).

Provenance & Evidence