Triethylamine → 4-{[(3R)-1-(2-Azidoethyl)piperidin-3-yl]methyl}-N-(3,4-dichlorophenyl)piperazine-1-carboxamide

HRID 2371177Notes

Reaction equation

HRID 2371177 reaction equation
CS(Cl)(=O)=O.[Cl:6][C:7]1[CH:8]=[C:9]([NH:14][C:15]([N:17]2[CH2:22][CH2:21][N:20]([CH2:23][C@@H:24]3[CH2:29][CH2:28][CH2:27][N:26]([CH2:30][CH2:31]O)[CH2:25]3)[CH2:19][CH2:18]2)=[O:16])[CH:10]=[CH:11][C:12]=1[Cl:13].C(N(CC)CC)C.[N-:40]=[N+:41]=[N-:42].[Na+]>ClCCl.O>[N:40]([CH2:31][CH2:30][N:26]1[CH2:27][CH2:28][CH2:29][C@@H:24]([CH2:23][N:20]2[CH2:21][CH2:22][N:17]([C:15]([NH:14][C:9]3[CH:10]=[CH:11][C:12]([Cl:13])=[C:7]([Cl:6])[CH:8]=3)=[O:16])[CH2:18][CH2:19]2)[CH2:25]1)=[N+:41]=[N-:42]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 57656840N-(3,4-Dichlorophenyl)-4-{[(3S)-1-(2-hydroxyethyl)piperidin-3-yl]methyl}piperazine-1-carboxamide

Product 1

HCID 866294184-{[(3R)-1-(2-Azidoethyl)piperidin-3-yl]methyl}-N-(3,4-dichlorophenyl)piperazine-1-carboxamideYield 5.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Methane sulphonyl chloride (0.4 ml) was added to a solution of N-(3,4-dichlorophenyl)-4-{[(3S)-1-(2-hydroxyethyl)piperidin-3-yl]methyl}piperazine-1-carboxamide (1.85 g, 4.45 mmol) in triethylamine (0.75 ml, 5.3 mmol) and dichloromethane (50 ml) at 0° C. under an atmosphere of argon. The reaction mixture was stirred at this temperature for one hour then water (100 ml) was added. The organic layer was separated, dried over magnesium carbonate, filtered then concentrated in vacuo. This material was then dissolved in anhydrous DMF (10 ml). Sodium azide (435 mg, 6.7 mmol) was added and the reaction mixture stirred overnight at 60° C. The reaction mixture was concentrated in vacuo and the residue separated between ethyl acetate (150 ml) and water (150 ml). The organic layer was separated, dried over magnesium carbonate, filtered then concentrated in vacuo onto silica gel (3 g). The resulting powder was subjected to chromatography (SiO2, 20 g) and the product eluted with a gradient of dichloromethane through to 10% methanolic ammonia/dichloromethane to yield the title compound as a white solid (105 mg)

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over magnesium carbonate
  3. filtrationfiltered
  4. concentrationthen concentrated in vacuo
  5. dissolutionThis material was then dissolved in anhydrous DMF (10 ml)
  6. stirringthe reaction mixture stirred overnight at 60° C
  7. concentrationThe reaction mixture was concentrated in vacuo
  8. customthe residue separated between ethyl acetate (150 ml) and water (150 ml)
  9. customThe organic layer was separated
  10. dry with materialdried over magnesium carbonate
  11. filtrationfiltered
  12. concentrationthen concentrated in vacuo onto silica gel (3 g)
  13. washthe product eluted with a gradient of dichloromethane through to 10% methanolic ammonia/dichloromethane

Sources & evidence

ORD record
ord-342f8acb1d314fa4be5d778306ee04e8
Source dataset
uspto-grants-2014_04
Patent number
US08710224B2

Reaction notes

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