反应详情

(+/−)-4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoic acid (Intermediate 26, 1.0 eq.), 1-hydrobenzotriazole hydrate (1.2 eq.), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.2 eq.), beta-alanine methyl ester hydrochloride (1.1 eq.), and triethylamine (1.3 eq.) were combined in anhydrous dichloromethane in a similar manner as described in the experimental for intermediate 27 to provide (+/−)-3-{4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid methyl ester which was resolved via chiral chromatography to provide the title compound. Preparative chiral SFC: (Chiralpak AD-H column, 21 mm×25 cm, 40% methanol/carbon dioxide eluent, 0.2% isopropylamine modifier, 65.0 mL/min flow rate, 2.71 retention time); 1H NMR (400 MHz, CDCl3) δ 7.63-7.69 (m, 2H), 7.58 (t, J=3.9 Hz, 2H), 7.45-7.51 (m, 3H), 7.41 (ddd, J=8.4, 7.0, 1.6 Hz, 1H), 7.14 (ddd, J=8.0, 6.9, 1.2 Hz, 1H), 6.72 (t, J=6.0 Hz, 1H), 5.31 (dd, J=9.7, 6.7 Hz, 1H), 4.75 (d, J=6.8 Hz, 1H), 3.69 (q, J=6.2 Hz, 5H), 2.55-2.71 (m, 3H), 2.28 (d, J=0.8 Hz, 3H), 1.95 (ddd, J=11.2, 8.0, 3.0 Hz, 1H), 1.78 (dd, J=11.1, 9.0 Hz, 1H), 1.64-1.72 (m, 2H), 1.15 (s, 3H), 1.08 (s, 3H); MS (M+1): 460.4.