Sodium Bicarbonate → 1-{[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl}-2-[(1-cyclopropylpiperidin-4-yl)carbamoyl]-1H-benzimidazole-5-carboxylic acid

HRID 18583노트

반응식

HRID 18583 반응식
Cl.Cl.[CH:3]1([N:6]2[CH2:11][CH2:10][CH:9]([NH2:12])[CH2:8][CH2:7]2)[CH2:5][CH2:4]1.C([O-])(O)=[O:14].[Na+].C[O:19][C:20]([C:22]1[CH:46]=[CH:45][C:25]2[N:26]([CH2:33][C:34]3[CH:38]=[C:37]([C:39]4[S:40][C:41]([Cl:44])=[CH:42][CH:43]=4)[O:36][N:35]=3)[C:27]([C:29](Cl)(Cl)Cl)=[N:28][C:24]=2[CH:23]=1)=[O:21]>CC#N.O>[Cl:44][C:41]1[S:40][C:39]([C:37]2[O:36][N:35]=[C:34]([CH2:33][N:26]3[C:25]4[CH:45]=[CH:46][C:22]([C:20]([OH:19])=[O:21])=[CH:23][C:24]=4[N:28]=[C:27]3[C:29](=[O:14])[NH:12][CH:9]3[CH2:10][CH2:11][N:6]([CH:3]4[CH2:5][CH2:4]4)[CH2:7][CH2:8]3)[CH:38]=2)=[CH:43][CH:42]=1

참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 467352434-Amino-1-cyclopropylpiperidine dihydrochlorideHCID 686154671-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-trichloromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester

생성물 1

HCID 533163871-{[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl}-2-[(1-cyclopropylpiperidin-4-yl)carbamoyl]-1H-benzimidazole-5-carboxylic acid

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매2회

실험 절차

21.0 mg (0.098 mmol) (1-Cyclopropyl-piperidin-4-ylamine-dihydrochloride were dissolved in 3 mL CH3CN and 3 mL water. 82.3 mg (0.98 mmol, 10 equiv.) NaHCO3 were added. Finally, a solution of 48.1 mg (0.098 mmol) 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-trichloromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester in 2 mL CH3CN was added and the resulting mixture was stirred vigorously for 3 h under reflux. The mixture was concentrated under reduced pressure. The residue was purified by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid) to give pure 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid in form of a colorless amorphous solid.

후처리

  1. temperatureunder reflux
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customThe residue was purified by preparative RP-HPLC (CH3CN/H2O gradient+0.05% formic acid)

출처 및 근거

ORD 기록
ord-92ccf70ce53f471bbdbdfab1d88a3f05
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741341B2

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