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

HRID 659673ノート

反応式

HRID 659673 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-efdcdd85fc13461cb68a143a20b3800a
出典データセット
uspto-grants-2011_12
特許番号
US08080571B2

反応ノート

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