Ammonia → [4-(5-Amino-3-methyl-pyridin-2-yl)-piperazin-1-yl]-(2,6-difluoro-phenyl)-methanone

HRID 1993655Notes

Reaction equation

HRID 1993655 reaction equation
[O-]S(S([O-])=O)=O.[Na+].[Na+].N.[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=1[C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:26]2[C:31]([CH3:32])=[CH:30][C:29]([N+:33]([O-])=O)=[CH:28][N:27]=2)[CH2:22][CH2:21]1)=[O:19]>C1COCC1.O>[NH2:33][C:29]1[CH:30]=[C:31]([CH3:32])[C:26]([N:23]2[CH2:22][CH2:21][N:20]([C:18]([C:12]3[C:13]([F:17])=[CH:14][CH:15]=[CH:16][C:11]=3[F:10])=[O:19])[CH2:25][CH2:24]2)=[N:27][CH:28]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 24489Sodium DithioniteHCID 68540471(2,6-Difluoro-phenyl)-[4-(3-methyl-5-nitro-pyridin-2-yl)-piperazin-1-yl]-methanone

Product 1

HCID 68540113[4-(5-Amino-3-methyl-pyridin-2-yl)-piperazin-1-yl]-(2,6-difluoro-phenyl)-methanoneYield 44%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

Add Na2S2O4 (10 equiv.) and aqueous ammonia (3 mL/mmol, 32%) to a solution of (2,6-difluoro-phenyl)-[4-(3-methyl-5-nitro-pyridin-2-yl)-piperazin-1-yl]-methanone (3 g, 8.29 mmol) in THF/H2O (166 mL, 1:1). Stir for 30 min., then separate layers. Extract the aqueous layer with DCM, EtOAc and isopropyl alcohol/EtOAc. Combine organic layers and dry over Na2SO4, filter and remove solvent under reduced pressure. Subject crude to a Varian™ SCX column and wash the column with MeOH and then flush off the product with 2 M NH3 in MeOH to obtain 1.2 g of [4-(5-amino-3-methyl-pyridin-2-yl)-piperazin-1-yl]-(2,6-difluoro-phenyl)-methanone (44% yield). ES+(m/z): 333 [M+1]

Workup

  1. extractionExtract the aqueous layer with DCM, EtOAc and isopropyl alcohol/EtOAc
  2. dry with materialCombine organic layers and dry over Na2SO4
  3. filtrationfilter
  4. customremove solvent under reduced pressure
  5. washwash the column with MeOH
  6. customflush off the product with 2 M NH3 in MeOH

Sources & evidence

ORD record
ord-320f788b0a6e4e41a97ac5392760f6d4
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

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