1,2-Dichloroethane → N-Carbamoylmethyl-N-[4-(2-chloro-phenyl)-pyridin-3-yl]-3,5-bis-trifluoromethyl-benzamide

HRID 878118Notes

Reaction equation

HRID 878118 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]C)[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.C(Cl)CCl.ON1C2N=CC=CC=2N=N1.[Cl-].[NH4+].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[C:32]([CH2:31][N:14]([C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:8]=1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[Cl:1])[C:15](=[O:30])[C:16]1[CH:17]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:19]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:21]=1)(=[O:35])[NH2:33]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 25517Ammonium Chloride2×HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 86670725HCID 86670725, compound

Product 1

HCID 86670741N-Carbamoylmethyl-N-[4-(2-chloro-phenyl)-pyridin-3-yl]-3,5-bis-trifluoromethyl-benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of {(3,5-bis-trifluoromethyl-benzoyl)-[4-(2-chloro-phenyl)-pyridin-3-yl]-amino}-acetic acid (0.15 g, 298 μmol, example 102, intermediate) and EDC (172 mg, 895 μmol) in DMF (2 mL) was treated with 1-hydroxy-7-azabenzotriazole (122 mg, 895 μmol, CAS RN 39968-33-7) and stirred at room temperature for 20 min. to give a yellow solution. Ammonium chloride (160 mg, 2.98 mmol) and DIPEA (386 mg, 521 μL, 2.98 mmol) were added and the reaction was stirred for another 3.75 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 solid (0.099 g; 66%). MS (ESI): m/z=502.07 [M+H]+.

Workup

  1. customto give a yellow solution
  2. stirringthe reaction was stirred for another 3.75 h
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted twice with EtOAc
  5. washThe organic layers were washed twice with water and once with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. additiontreated with silica gel
  9. customevaporated
  10. customThe compound was purified by silica gel chromatography on a 10 g column
  11. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)

Sources & evidence

ORD record
ord-2f6312dba9d0494ab00555a90f0e5efd
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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