Citric Acid → N-Butyloxycarbonyl-3-(3-imidazol-1-ylmethylphenyl)-5-iso-butylthiophene-2-sulfonamide

HRID 659673노트

반응식

HRID 659673 반응식
[N:1]1([CH2:6][C:7]2[CH:8]=[C:9]([C:13]3[CH:17]=[C:16]([CH2:18][CH:19]([CH3:21])[CH3:20])[S:15][C:14]=3[S:22]([NH:25]C(C)(C)C)(=[O:24])=[O:23])[CH:10]=[CH:11][CH:12]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.B(Cl)(Cl)Cl.N1(C2C=CC=CN=2)CCCC1.Cl[C:46]([O:48][CH2:49][CH2:50][CH2:51][CH3:52])=[O:47].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl>[CH2:49]([O:48][C:46]([NH:25][S:22]([C:14]1[S:15][C:16]([CH2:18][CH:19]([CH3:20])[CH3:21])=[CH:17][C:13]=1[C:9]1[CH:10]=[CH:11][CH:12]=[C:7]([CH2:6][N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)[CH:8]=1)(=[O:23])=[O:24])=[O:47])[CH2:50][CH2:51][CH3:52]

참가 물질

7

반응물 5

HCID 311Citric AcidHCID 25135Boron TrichlorideHCID 61140Butyl chloroformateHCID 110190202-(Pyrrolidin-1-yl)pyridineHCID 671329423-(3-imidazol-1-ylmethylphenyl)-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide

생성물 1

HCID 56964910N-Butyloxycarbonyl-3-(3-imidazol-1-ylmethylphenyl)-5-iso-butylthiophene-2-sulfonamide수율 59%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 3-(3-imidazol-1-ylmethylphenyl)-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (68.8 mg, 0.159 mmol; see step (f)) in CH2Cl2 (2 mL) was added BCl3 (0.6 mL, 1.0 M in hexane) and the reaction mixture was stirred for 1 h at ambient temperature. The reaction mixture was concentrated in vacuo. Water (5 mL) was added to the residue and this was then extracted with EtOAc. The combined organic phase was washed with water and brine and dried over anhydrous MgSO4, concentrated in vacuo. To the crude product dissolved in pyridine (1.5 mL) was added pyrrolidinopyridine (69.8 mg, 0.471 mmol) and butyl chloroformate (202.8 μL, 1.59 mmol) and the reaction mixture was stirred overnight. Citric acid (3 mL, 10% aq) was added to the reaction mixture, extracted with EtOAc, dried (over anhydrous MgSO4), concentrated in vacuo, and the residue was purified by flash chromatography using MeOH:CH2Cl2 (6:94) as eluent to give the title compound in 59% yield, over two steps, (44.4 mg, 0.093 mmol).

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionWater (5 mL) was added to the residue
  3. extractionthis was then extracted with EtOAc
  4. washThe combined organic phase was washed with water and brine
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationconcentrated in vacuo
  7. dissolutionTo the crude product dissolved in pyridine (1.5 mL)
  8. stirringthe reaction mixture was stirred overnight
  9. extractionextracted with EtOAc
  10. dry with materialdried (over anhydrous MgSO4)
  11. concentrationconcentrated in vacuo
  12. customthe residue was purified by flash chromatography

출처 및 근거

ORD 기록
ord-efdcdd85fc13461cb68a143a20b3800a
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08080571B2

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