Acetic Acid → N-[1-(cyclobutylmethyl)-3-methylpyrrolidin-3-yl]-N-[(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]cyclohexanecarboxamide

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N-[(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]-N-(3-methylpyrrolidin-3-yl)cyclohexanecarboxamide (300 mg, 0.786 mmol), cyclobutanecarbaldehyde (99 mg, 1.180 mmol), and acetic acid (0.090 ml, 1.573 mmol) were combined in CH2Cl2 (70 ml). Sodium triacetoxyborohydride (333 mg, 1.573 mmol) was added and the reaction stirred for 2.5 hours. The reaction mixture was partitioned between CH2Cl2 and satd. bicarb, the aqueous portion extracted 3×CH2Cl2, and the organic portion dried (Na2SO4) then concentrated in vacuo. The resulting material was purified in two batches by reversed phase chromatography (15-95% ACN in water (with 0.5 ml/l NH4OH) over 20 min at 50 ml/min, 30×100 mm Phenomenex Gemini C18 column). Desired fractions were combined and concentrated in vacuo. HRMS [M+H]1+ 450.3099. 1H NMR (400 MHz, CDCl3): δ 7.62-7.55 (m, 3 H); 7.42 (d, J=8.5 Hz, 1 H); 7.29 (t, J=7.6 Hz, 1 H); 4.44 (s, 2 H); 3.80 (s, 3 H); 2.99 (d, J=10.0 Hz, 1 H); 2.85 (d, J=10.2 Hz, 1 H); 2.53 (t, J=7.9 Hz, 1 H); 2.47-2.35 (m, 4 H); 2.09-1.92 (m, 5 H); 1.92-1.64 (m, 14 H); 1.28-0.99 (m, 3 H). 210 mg, 59%.

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