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

HRID 18554

반응식

HRID 18554 반응식
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([CH2:11][N:12]2[C:16]3[CH:17]=[CH:18][CH:19]=[C:20]([C:21]([OH:23])=[O:22])[C:15]=3[N:14]=[C:13]2[C:24](=[O:35])[NH:25][CH:26]2[CH2:31][CH2:30][N:29]([CH:32]([CH3:34])[CH3:33])[CH2:28][CH2:27]2)=[O:10])=[N:6][CH:7]=1.[CH:36]1([CH2:39]O)[CH2:38][CH2:37]1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH:36]1([CH2:39][O:22][C:21]([C:20]2[C:15]3[N:14]=[C:13]([C:24](=[O:35])[NH:25][CH:26]4[CH2:31][CH2:30][N:29]([CH:32]([CH3:33])[CH3:34])[CH2:28][CH2:27]4)[N:12]([CH2:11][C:9](=[O:10])[NH:8][C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=4)[C:16]=3[CH:17]=[CH:18][CH:19]=2)=[O:23])[CH2:38][CH2:37]1

참가 물질

6

반응물 3

HCID 10868Dicyclohexylcarbodiimide2회HCID 75644Cyclopropanemethanol2회HCID 113754531-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid

생성물 1

HCID 670125761-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid cyclopropylmethyl ester

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매2회HCID 6344Dichloromethane용매

실험 절차

325.1 mg (0.57 mmol) 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid were dissolved in 20 mL CH2Cl2. Subsequently 470 μl (5.7 mmol) cyclopropyl-methanol, 152.2 mg (0.74 mmol) DCC and 6.9 mg DMAP were added. The resulting mixture was stirred at room temperature for 16 h. The next day further 100 μl (2.28 mmol) cyclopropyl-methanol, 58.6 mg (0.29 mmol) DCC and 20 mg DMAP were added and the reaction mixture was stirred for 48 h. The solvent was removed under vacuo. Final purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid) gave 1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-4-carboxylic acid cyclopropylmethyl ester as a white amorphous solid. The corresponding acetate was obtained by the following procedure: The above described material was dissolved in CH2Cl2 and washed with a saturated NaHCO3-solution. The organic layer was dried over anhydrous MgSO4 and concentrated. The resulting residue was diluted in 20 mL water containing 4 equiv. AcOH and lyophilized.

후처리

  1. stirringthe reaction mixture was stirred for 48 h
  2. customThe solvent was removed under vacuo
  3. customFinal purification by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid)

출처 및 근거

ORD 기록
ord-472d81f472804382830179b2c7da3b13
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741341B2

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