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 18623Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 18623
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

Komponenten

6

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel2×

Versuchsvorschrift

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 equivalents) NaHCO3 were added. Then, 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 and 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. (Under these conditions the methyl ester was hydrolyzed simultaneously!)

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-0b29770b36724e37ab658b18a17e9e36
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741341B2

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