Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → N-{4-Chloro-3-[5-chloro-1-methyl-6-(4-trifluoromethyl-piperidin-1-yl)-1H-benzimidazol-2-ylamino]-benzyl}-2,2-difluoro-propionamide

HRID 1258720Notes

Reaction equation

HRID 1258720 reaction equation
[F:1][C:2]([F:7])([CH3:6])[C:3](O)=[O:4].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][NH2:38])=[CH:35][C:34]=1[NH:41][C:42]1[N:46]([CH3:47])[C:45]2[CH:48]=[C:49]([N:53]3[CH2:58][CH2:57][CH:56]([C:59]([F:62])([F:61])[F:60])[CH2:55][CH2:54]3)[C:50]([Cl:52])=[CH:51][C:44]=2[N:43]=1>CN(C=O)C.[Cl-].[Na+].O>[Cl:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][NH:38][C:3](=[O:4])[C:2]([F:7])([F:1])[CH3:6])=[CH:35][C:34]=1[NH:41][C:42]1[N:46]([CH3:47])[C:45]2[CH:48]=[C:49]([N:53]3[CH2:54][CH2:55][CH:56]([C:59]([F:61])([F:60])[F:62])[CH2:57][CH2:58]3)[C:50]([Cl:52])=[CH:51][C:44]=2[N:43]=1

Participants

6

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27828252,2-Difluoropropionic acidHCID 679580774-Chloro-3-[5-chloro-1-methyl-6-(4-trifluoromethyl-piperidin-1-yl)-1H-benzo[d]imidazol-2-ylamino]benzylamine

Product 1

HCID 86674341N-{4-Chloro-3-[5-chloro-1-methyl-6-(4-trifluoromethyl-piperidin-1-yl)-1H-benzimidazol-2-ylamino]-benzyl}-2,2-difluoro-propionamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 2,2-difluoropropanoic acid (37 mg; 0.34 mmol), HBTU (129 mg; 0.34 mmol) and TEA (69 mg; 0.68 mmol) in DMF (1.5 mL) was stirred for 30 min at rt and added to a solution of 4-chloro-3-[5-chloro-1-methyl-6-(4-trifluoromethyl-piperidin-1-yl)-1H-benzo[d]imidazol-2-ylamino]benzylamine (161 mg; 0.34 mmol) in DMF (1.5 mL). The resulting mixture was stirred overnight at rt, poured into brine and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated and the residue was purified by column chromatography.

Workup

  1. stirringThe resulting mixture was stirred overnight at rt
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-60be103dc9ae4d64a5db50376d761147
Source dataset
uspto-grants-2013_06
Patent number
US08466186B2

Reaction notes

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