Triethylamine → N-{1-(1,4-Dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)-5-[4-(trifluoromethyl)phenyl]piperidin-3-yl}-cyclopentanecarboxamide

HRID 876258Notes

Reaction equation

HRID 876258 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][CH:10]1[CH2:15][CH:14]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)[CH2:13][N:12]([C:26]([N:28]2[CH2:37][CH2:36][C:31]3([O:35][CH2:34][CH2:33][O:32]3)[CH2:30][CH2:29]2)=[O:27])[CH2:11]1.[CH:38]1([C:43](Cl)=[O:44])[CH2:42][CH2:41][CH2:40][CH2:39]1>CN(C1C=CN=CC=1)C.ClCCl>[O:35]1[C:31]2([CH2:30][CH2:29][N:28]([C:26]([N:12]3[CH2:13][CH:14]([C:16]4[CH:21]=[CH:20][C:19]([C:22]([F:24])([F:25])[F:23])=[CH:18][CH:17]=4)[CH2:15][CH:10]([NH:9][C:43]([CH:38]4[CH2:42][CH2:41][CH2:40][CH2:39]4)=[O:44])[CH2:11]3)=[O:27])[CH2:37][CH2:36]2)[O:32][CH2:33][CH2:34]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 78284Cyclopentanecarbonyl chlorideHCID 66760651{3-Amino-5-[4-(trifluoromethyl)phenyl]piperidin-1-yl}(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)methanone hydrochloride

Product 1

HCID 66701500N-{1-(1,4-Dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)-5-[4-(trifluoromethyl)phenyl]piperidin-3-yl}-cyclopentanecarboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

177 μl of triethylamine (1.27 mmol) and 15.5 mg of DMAP (0.127 mmol) were added to a solution of the amine hydrochloride from Example 62A (200 mg, 0.422 mmol) in dichloromethane (10 ml), and 84 mg of cyclopentanecarbonyl chloride (0.633 mmol) were then added at 0° C. The reaction mixture was warmed to RT and stirred overnight. The reaction solution was washed with aqueous 1 N hydrogen chloride solution and the organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (RP18 column; acetonitrile/water gradient). Yield: 112 mg (52% of theory)

Workup

  1. additionwere then added at 0° C
  2. washThe reaction solution was washed with aqueous 1 N hydrogen chloride solution
  3. dry with materialthe organic phase was dried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by preparative HPLC (RP18 column; acetonitrile/water gradient)

Sources & evidence

ORD record
ord-0d52e676d10140808b8f3b98fc8fa8fb
Source dataset
uspto-grants-2015_03
Patent number
US08987248B2

Reaction notes

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