Toluene → 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid methyl ester

HRID 18520

반응식

HRID 18520 반응식
[CH3:1][O:2][C:3]([C:5]1[C:13]2[N:12]=[C:11]([C:14](=[O:25])[N:15](C(C)C)[CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[NH:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].Br[CH2:33][C:34]([NH:36][C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][N:38]=1)=[O:35].[C:44]1(C)[CH:49]=CC=C[CH:45]=1>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[C:13]2[N:12]=[C:11]([C:14](=[O:25])[NH:15][CH:16]3[CH2:21][CH2:20][N:19]([CH:44]([CH3:49])[CH3:45])[CH2:18][CH2:17]3)[N:10]([CH2:33][C:34](=[O:35])[NH:36][C:37]3[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][N:38]=3)[C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4]

참가 물질

6

반응물 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 34211102-Bromo-N-(5-chloro-2-pyridinyl)acetamideHCID 686173622-(Isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid methyl ester

생성물 1

HCID 114664091-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid methyl ester

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

100.8 mg (0.29 mmol) 2-(Isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid methyl ester were dissolved in 6 mL DMF. Subsequently 60.6 mg (0.44 mmol) K2CO3 and 87.5 mg (0.35 mmol) 2-bromo-N-(5-Chloro-pyridin-2-yl-)-acetamide were added and the resulting mixture was stirred for 3 h at 80° C. The reaction mixture was diluted with 60 mL toluene and washed with a sat. NaHCO3 solution and brine. The organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by preparative HPLC (CH3CN/H2O gradient+0.05% formic acid) to give 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid methyl ester as a white amorphous solid. The product was obtained as its hydroformiate.

후처리

  1. washwashed with a sat. NaHCO3 solution and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. customthe solvent was removed under reduced pressure
  4. customThe residue was purified by preparative HPLC (CH3CN/H2O gradient+0.05% formic acid)

출처 및 근거

ORD 기록
ord-9741d861ddb9467e980db0243530e544
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741341B2

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