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

HRID 258293Notes

Reaction equation

HRID 258293 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]23[CH2:24][CH:16]([C:17]4[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][C:22]=42)[C:15]2[C:10]3=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:4][CH2:3]1.N1C=CC=CC=1.[CH:31]1([CH2:36][C:37](Cl)=[O:38])[CH2:35][CH2:34][CH2:33][CH2:32]1.[OH-].[Na+]>C(Cl)Cl>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]2[CH:16]3[CH2:24][C:9]([CH2:8][N:5]4[CH2:6][CH2:7][CH:2]([NH:1][C:37](=[O:38])[CH2:36][CH:31]5[CH2:35][CH2:34][CH2:33][CH2:32]5)[CH2:3][CH2:4]4)([C:10]4[C:15]3=[CH:14][CH:13]=[CH:12][CH:11]=4)[C:22]=2[CH:21]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 14798Sodium HydroxideHCID 3485182Cyclopentylacetyl chlorideHCID 193809734-Amino-1-(2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)piperidine

Product 1

HCID 19381071N-(1-[2-Chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl]-4-piperidyl)-2-cyclopentylacetamideYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-fbd357da6ddb455a872846ebdadd0625
Source dataset
uspto-grants-1993_11
Patent number
US05266570

Reaction notes

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