Dimethylacetamide → HCID 9803868, compound

HRID 2298832Notes

Reaction equation

HRID 2298832 reaction equation
CC(N(C)C)=O.[CH3:7][C@H:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([CH3:14])[N:9]1[CH2:15][CH2:16][NH:17][C:18]([C@@H:20]1[CH2:25][CH2:24][CH2:23][CH2:22][NH:21]1)=[O:19].Cl[C:27]1[N:31](C(OC(C)(C)C)=O)[C:30]2[CH:39]=[CH:40][C:41]([C:43]([F:46])([F:45])[F:44])=[CH:42][C:29]=2[N:28]=1>C1(C)C(C)=CC=CC=1>[CH2:8]([NH:9][CH2:10][CH3:11])[CH3:7].[CH3:14][C@H:10]1[CH2:11][CH2:12][CH2:13][C@@H:8]([CH3:7])[N:9]1[CH2:15][CH2:16][NH:17][C:18]([C@@H:20]1[CH2:25][CH2:24][CH2:23][CH2:22][N:21]1[C:27]1[NH:28][C:29]2[CH:42]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:40]=[CH:39][C:30]=2[N:31]=1)=[O:19]

Participants

6

Reactant 3

HCID 31374DimethylacetamideHCID 12096144HCID 12096144, compoundHCID 12096145HCID 12096145, compound

Product 2

HCID 8021DiethylamineHCID 9803868HCID 9803868, compoundYield 48.6%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Conditions

Temperature
80 °C

Procedure

Dimethylacetamide (0.5 ml) was added to a mixture of (2S)-N2-2-[(cis)-2,6-dimethyl-1-piperidinyl]ethyl-2-piperidinecarboxamide (134 mg) [see Preparation 15] and tert-butyl 2-chloro-5-(trifluoromethyl)-1H-1,3-benzimidazole-1-carboxylate (463 mg) [see Preparation 16]. The reaction mixture was heated to 80° C. for 12 hours, after which time the mixture was reduced to low volume, xylene (50 ml) was added, and all solvent was removed under reduced pressure. The residue was partitioned between saturated sodium bicarbonate solution and ethyl acetate, the organic layer was separated, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 100:0, changing to 98:2, by volume, ethyl acetate:diethylamine, in 0.5% increments, to afford (2S)-N2-2-[(cis)-2,6-dimethyl-1-piperidinyl]ethyl-1-[6-(trifluoromethyl )-1H-1,3-benzimidazol-2-yl]-2-piperidinecarboxamide (55 mg) as a white solid.

Workup

  1. additionwas added
  2. customall solvent was removed under reduced pressure
  3. customThe residue was partitioned between saturated sodium bicarbonate solution and ethyl acetate
  4. customthe organic layer was separated
  5. dry with materialdried over magnesium sulphate
  6. customthe solvent removed under reduced pressure
  7. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 100:0

Sources & evidence

ORD record
ord-dc5c1c97ede74136b723e9f9ccdabd9a
Source dataset
uspto-grants-2002_12
Patent number
US06495549B1

Reaction notes

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