Cyclohexanecarbonyl chloride → N-[(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]-N-{[3-(4-methylpiperazin-1-yl)-2,3,4,5-tetrahydrooxepin-3-yl]methyl}cyclohexanecarboxamide

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Reaction Steps

To a solution of 1-methyl-3-[({[3-(4-methylpiperazin-1-yl)-2,3,4,5-tetrahydrooxepin-3-yl]methyl}amino)methyl]quinolin-2(1H)-one (100 mg, 0.252 mmole) in CH2Cl2 (1.5 ml) was added TEA (0.053 ml, 0.378 mmole) then cyclohexanecarbonyl chloride (0.044 ml, 0.328 mmole). After 2 hr the mixture was concentrated. The crude material was purified by preparative reversed-phase HPLC (30×150 mm Waters Sunfire, 5-50% CH3CN/water containing 0.1% TFA over 20 min at 50 mL/min). Fractions containing the product were pooled and concentrated. The residue was taken up in MeOH then passed through Dowex 1×2-400 ion exchange resin (prewashed with 1M NaOH, H2O, MeOH) washing with MeOH. The filtrate was concentrated to give the title compound as a white solid (89 mg, 70%). 1H-NMR (CDCl3, 500 MHz) d 7.58 (t, J=8.30 Hz, 1 H), 7.52 (d, J=7.57 Hz, 1 H), 7.39 (d, J=8.30 Hz, 1 H), 7.25 (m, 1 H), 7.22 (s, 1 H), 6.21 (d, J=6.34 Hz, 1 H), 5.24 (d, J=19.77 Hz, 1 H), 4.60 (m, 2 H), 4.44 (d, J=13.19 Hz, 1 H), 4.24 (d, J=14.16 Hz, 1 H), 4.05 (d, J=13.18 Hz, 1 H), 3.78 (s, 3 H), 3.07 (d, J=14.16 Hz, 1 H), 2.74 (m, 1 H), 2.62 (m, 2 H), 2.45-2.21 (m, 6 H), 2.26 (s, 3 H), 2.16-2.05 (m, 2 H), 1.82-1.48 (m, 9 H), 1.25-1.06 (m, 3 H). HRMS (M+H)+ calculated 507.3330. found 507.3329.

Provenance & Evidence