Dimethylacetamide → Ammonia

HRID 1635634Notes

Reaction equation

HRID 1635634 reaction equation
CC([N:4](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]=[C:40]([F:44])[C:41]([F:43])=[CH:42][C:29]=2[N:28]=1>C1(C)C(C)=CC=CC=1>[NH3:4].[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]([F:43])[C:40]([F:44])=[CH:39][C:30]=2[N:31]=1)=[O:19]

Participants

6

Reactant 3

HCID 31374DimethylacetamideHCID 12096144HCID 12096144, compoundHCID 12096150HCID 12096150, compound

Product 2

HCID 222AmmoniaHCID 9802191HCID 9802191, compound

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Conditions

Temperature
60 °C

Procedure

Dimethylacetamide (1 ml) was added to a mixture of (2S)-N2-2-[(cis)-2,6-dimethyl-1-piperidinyl]ethyl-2-piperidinecarboxamide (267 mg) [see Preparation 15] and tert-butyl 2-chloro-5,6-difluoro-1H-1,3-benzimidazole-1-carboxylate (350 mg) [see Preparation 43]. The reaction mixture was heated to 60° C. for 4 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 dissolved in dichloromethane (10 ml) and treated with trifluoroacetic acid (5 ml). After 2 hours stirring at room temperature, the mixture was reduced to low volume. The residue was dissolved in dichloromethane, washed with saturated sodium bicarbonate solution, dried over magnesium sulphate and evaporated to dryness. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 100:0, changing 95:4.5:0.5 dichlomethane:methanol:0.880 aqueous ammonia solution to afford (2S)-N2-2-[(cis)-2,6-dimethyl-1-piperidinyl]ethyl-1-[5,6-difluoro-1H-1,3-benzimidazol-2-yl]-2-piperidinecarboxamide (50 mg) as a white solid.

Workup

  1. additionwas added
  2. customall solvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in dichloromethane (10 ml)
  4. additiontreated with trifluoroacetic acid (5 ml)
  5. dissolutionThe residue was dissolved in dichloromethane
  6. washwashed with saturated sodium bicarbonate solution
  7. dry with materialdried over magnesium sulphate
  8. customevaporated to dryness
  9. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 100:0

Sources & evidence

ORD record
ord-bf71b292463a4344b16c28adfadd8c66
Source dataset
uspto-grants-2003_01
Patent number
US06509464B1

Reaction notes

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