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 1258720Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1258720
[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

Komponenten

6

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-60be103dc9ae4d64a5db50376d761147
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08466186B2

Notizen zur Reaktion

Wird geladen…