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

HRID 878118ノート

反応式

HRID 878118 の反応式
[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]

参加物

8

反応物 5

HCID 111,2-DichloroethaneHCID 25517Ammonium Chloride2 回HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 86670725HCID 86670725、化合物

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-2f6312dba9d0494ab00555a90f0e5efd
出典データセット
uspto-grants-2015_03
特許番号
US08987307B2

反応ノート

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