Pyridine → N-(1-[2-Chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl]-4-piperidyl)-2-cyclopentylacetamide

To a stirred cold (ice bath) solution of 4-amino-1-[2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl]piperidine (339 mg, 1 mmol, described in Example 7b) and pyridine (158 mg, 2 mmol) in methylene chloride (6.7 mL) was added cyclopentylacetyl chloride (161 mg, 1.1 mmol). After 15 min, the reaction was allowed to warm to ambient temperature and stirred for 18 h. The reaction was added methylene chloride (75 mL) and 1N sodium hydroxide (50 mL). The aqueous layer was extracted with methylene chloride (50 mL). The organic layers were combined and washed with 1N sodium hydroxide (2×50 mL), brine (35 mL) and dried (sodium sulfate). The solution was filtered and concentrated to give a foam. This material was chromatographed over silica gel (eluting in sequence with 1) methylene chloride; 2) 3:97 methanol:methylene chloride) and crystallized with ether to give the title compound as a white solid (323 mg, 72%), mp 149.5°-150.5° C.; MS(CI): 449 (M+H); NMR (300 MHz,DMSO-d6): 1.02-1.17(m, 2H), 1.26-1.74(m, 10H), 2.01(d, 2H, 2H, J=6.0 Hz), 2.09(m, 1H), 2.18-2.32(m, 2H), 2.47(m, 2H), 2.86-3.00(m, 2H), 3.28(d, 1H, J=14 Hz), 3.37(d, 1H, J=14 Hz), 3.54(m, 1H), 4.33(s, 1H), 6.89-7.00(m, 3H), 7.15-7.31(m, 4H), 7.61(d, 1H, J=7.7 Hz).

1. extractionThe aqueous layer was extracted with methylene chloride (50 mL)
2. washwashed with 1N sodium hydroxide (2×50 mL), brine (35 mL)
3. dry with materialdried (sodium sulfate)
4. filtrationThe solution was filtered
5. concentrationconcentrated
6. customto give a foam
7. customThis material was chromatographed over silica gel (eluting in sequence with 1) methylene chloride
8. custom2) 3:97 methanol:methylene chloride) and crystallized with ether

ORD record

ord-fbd357da6ddb455a872846ebdadd0625

Source dataset

uspto-grants-1993_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05266570