Diisopropylcarbodiimide → 2-(2-chloro-5-{[(1-trifluoromethyl-cyclopropanecarbonyl)-amino]-methyl}-phenylamino)-6-methoxy-1-methyl-1H-benzimidazole-5-carboxylic acid

HRID 1410221노트

반응식

HRID 1410221 반응식
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][NH:7][C:8]([C:10]2([C:13]([F:16])([F:15])[F:14])[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[N:19]=[C:20]=S.[NH2:22][C:23]1[C:24]([NH:34][CH3:35])=[CH:25][C:26]([O:32][CH3:33])=[C:27]([CH:31]=1)[C:28]([OH:30])=[O:29].FC(F)(F)C(=N[Si](C)(C)C)O[Si](C)(C)C.CC(C)N=C=NC(C)C>CN(C=O)C.C(O)(=O)C>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][NH:7][C:8]([C:10]2([C:13]([F:16])([F:15])[F:14])[CH2:12][CH2:11]2)=[O:9])=[CH:4][C:3]=1[NH:19][C:20]1[N:34]([CH3:35])[C:24]2[CH:25]=[C:26]([O:32][CH3:33])[C:27]([C:28]([OH:30])=[O:29])=[CH:31][C:23]=2[N:22]=1

참가 물질

7

반응물 4

HCID 12734DiisopropylcarbodiimideHCID 94358Bis(trimethylsilyl)trifluoroacetamideHCID 595298385-Amino-2-methoxy-4-(methylamino)benzoic acidHCID 86646336N-(4-Chloro-3-isothiocyanatobenzyl)-1-(trifluoromethyl)cyclopropane carboxamide

생성물 1

HCID 595298032-(2-chloro-5-{[(1-trifluoromethyl-cyclopropanecarbonyl)-amino]-methyl}-phenylamino)-6-methoxy-1-methyl-1H-benzimidazole-5-carboxylic acid

시약·촉매·용매 2

HCID 176Acetic Acid용매HCID 6228Dimethylformamide용매

실험 절차

A mixture of N-(4-chloro-3-isothiocyanatobenzyl)-1-(trifluoromethyl)cyclopropane carboxamide (1.71 g; 5.10 mmol) and 5-amino-2-methoxy-4-(methylamino)benzoic acid (1.00 g; 1.00 mmol) in DMF (20 mL) was stirred over night at rt. The mixture was thereafter heated to 60° C. and BSTFA (1.44 g; 5.61 mmol) was added and stirred for 1 h before the addition of DIC (0.772 g; 6.12 mmol). The resulting mixture was stirred at 80° C. for 3 h. Acetic acid (2 mL) was added and the mixture was concentrated and the residue poured in aqueous NaOH (2 M) and pH adjusted to −3-4. The mixture was extracted with EtOAc and the organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was recrystallized from EtOAc/petroleum ether to give the sub-title compound. Yield: 0.570 g (22%).

후처리

  1. temperatureThe mixture was thereafter heated to 60° C.
  2. stirringThe resulting mixture was stirred at 80° C. for 3 h
  3. concentrationthe mixture was concentrated
  4. additionthe residue poured in aqueous NaOH (2 M)
  5. extractionThe mixture was extracted with EtOAc
  6. washthe organic extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was recrystallized from EtOAc/petroleum ether

출처 및 근거

ORD 기록
ord-19dd33d443ba40c4a428892582770567
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921405B2

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