Ammonium Chloride → N-[4-(2-Chloro-phenyl)-pyridin-3-yl]-N-dimethylcarbamoylmethyl-3,5-bis-trifluoromethyl-benzamide

HRID 878119Notes

Reaction equation

HRID 878119 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[N:14]([CH2:31][C:32](=[O:35])[NH:33][CH3:34])[C:15](=[O:30])[C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=1.[CH3:36]N(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.C(NCC)C.CCN(C(C)C)C(C)C.[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[N:14]([CH2:31][C:32](=[O:35])[N:33]([CH3:36])[CH3:34])[C:15](=[O:30])[C:16]1[CH:17]=[C:18]([C:26]([F:27])([F:28])[F:29])[CH:19]=[C:20]([C:22]([F:25])([F:23])[F:24])[CH:21]=1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10197650Diethylammonium chlorideHCID 86670725HCID 86670725, compound

Product 1

HCID 86670742N-[4-(2-Chloro-phenyl)-pyridin-3-yl]-N-dimethylcarbamoylmethyl-3,5-bis-trifluoromethyl-benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of {(3,5-bis-trifluoromethyl-benzoyl)-[4-(2-chloro-phenyl)-pyridin-3-yl]-amino}-acetic acid (0.15 g, 298 μmol, example 102, intermediate), HATU (136 mg, 358 μmol) and diethylamin hydrochloride (29.2 mg, 358 μmol) in DMF (2 mL) was treated with DIPEA (116 mg, 156 μL, 895 μmol) and stirred at room temperature for 1.75 h. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were washed twice with water and once with brine, dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 10 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Light yellow foam (0.127 g; 80%). MS (ESI): m/z=530.12 [M+H]+.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted twice with EtOAc
  3. washThe organic layers were washed twice with water and once with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. additiontreated with silica gel
  7. customevaporated
  8. customThe compound was purified by silica gel chromatography on a 10 g column
  9. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)

Sources & evidence

ORD record
ord-4efdbe4786914ef09a85045abfcf0533
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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