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

HRID 410094

반응식

HRID 410094 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 176Acetic Acid용매HCID 6342Acetonitrile용매

실험 절차

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.

후처리

  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)]

출처 및 근거

ORD 기록
ord-0b47fcdd7a18489ca43242e7456eac42
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759537B2

연결된 노트

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