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

HRID 410094

反応式

HRID 410094 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 6342Acetonitrile溶媒

実験手順

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.

後処理

  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)]

出典と根拠

ORDレコード
ord-0b47fcdd7a18489ca43242e7456eac42
出典データセット
uspto-grants-2014_06
特許番号
US08759537B2

関連ノート

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