Diisopropylcarbodiimide → 2-{2,6-dichloro-3-[(2,2-dimethyl-propionylamino)-methyl]-phenylamino}-6-(2,2-difluoro-ethoxy)-1H-benzimidazole-5-carboxylic acid

HRID 410094

Reaktionsgleichung

Reaktionsgleichung von HRID 410094
[F:1][CH:2]([F:16])[CH2:3][O:4][C:5]1[CH:13]=[C:12]([NH2:14])[C:11]([NH2:15])=[CH:10][C:6]=1[C:7]([OH:9])=[O:8].[Cl:17][C:18]1[C:31]([N:32]=[C:33]=S)=[C:30]([Cl:35])[CH:29]=[CH:28][C:19]=1[CH2:20][NH:21][C:22](=[O:27])[C:23]([CH3:26])([CH3:25])[CH3:24].FC(F)(F)C(=N[Si](C)(C)C)O[Si](C)(C)C.CC(C)N=C=NC(C)C>CC(O)=O.CC#N>[Cl:17][C:18]1[C:19]([CH2:20][NH:21][C:22](=[O:27])[C:23]([CH3:24])([CH3:25])[CH3:26])=[CH:28][CH:29]=[C:30]([Cl:35])[C:31]=1[NH:32][C:33]1[NH:14][C:12]2[CH:13]=[C:5]([O:4][CH2:3][CH:2]([F:16])[F:1])[C:6]([C:7]([OH:9])=[O:8])=[CH:10][C:11]=2[N:15]=1

Komponenten

7

Edukt 4

HCID 12734DiisopropylcarbodiimideHCID 94358Bis(trimethylsilyl)trifluoroacetamideHCID 56840192N-[(2,4-dichloro-3-isothiocyanatophenyl)methyl]-2,2-dimethylpropanamideHCID 871397232-(2,2-Difluoro-ethoxy)-4,5-diamino-benzoic acid

Produkt 1

HCID 1784473262-{2,6-dichloro-3-[(2,2-dimethyl-propionylamino)-methyl]-phenylamino}-6-(2,2-difluoro-ethoxy)-1H-benzimidazole-5-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

A mixture of 2-(2,2-difluoro-ethoxy)-4,5-diamino-benzoic acid (732 mg, 3.15 mmol), N-(2,4-dichloro-3-isothiocyanato-benzyl)-2,2-dimethyl-propionamide (1.00 g, 3.15 mmol) and MeCN (15 mL) is stirred for 48 h, then BSTFA (1.03 mL, 3.15 mmol) is added and it is stirred at reflux for 10 min. Then DIC (0.494 mL, 3.15 mmol) is added and it is stirred for another 4 h. The mixture is cooled to rt, diluted with HOAc and concentrated. The residue is stirred with 1N NaOH, filtered and the filtrate is acidified with 4N HCl, extracted with EtOAc and purified via chromatography [DCM→DCM+10% EtOH/HOAc (95:5)] to give the subtitle compound.

Aufarbeitung

  1. stirringit is stirred
  2. temperatureat reflux for 10 min
  3. stirringit is stirred for another 4 h
  4. concentrationconcentrated
  5. stirringThe residue is stirred with 1N NaOH
  6. filtrationfiltered
  7. extractionextracted with EtOAc
  8. custompurified via chromatography [DCM→DCM+10% EtOH/HOAc (95:5)]

Quellen und Nachweise

ORD-Eintrag
ord-0b47fcdd7a18489ca43242e7456eac42
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759537B2

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