Citric Acid → N-Butyloxycarbonyl-3-[3-(2-benzoimidazol-1-ylacetyl)phenyl]-5-iso-butyl-thiophene-2-sulfonamide

HRID 659703Notes

Reaction equation

HRID 659703 reaction equation
[N:1]1([CH2:10][C:11]([C:13]2[CH:14]=[C:15]([C:19]3[CH:23]=[C:22]([CH2:24][CH:25]([CH3:27])[CH3:26])[S:21][C:20]=3[S:28]([NH:31]C(C)(C)C)(=[O:30])=[O:29])[CH:16]=[CH:17][CH:18]=2)=[O:12])[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.C1(OC)C=CC=CC=1.N1(C2C=CC=CN=2)CCCC1.Cl[C:56]([O:58][CH2:59][CH2:60][CH2:61][CH3:62])=[O:57].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)(C(F)(F)F)=O>[CH2:59]([O:58][C:56]([NH:31][S:28]([C:20]1[S:21][C:22]([CH2:24][CH:25]([CH3:27])[CH3:26])=[CH:23][C:19]=1[C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([C:11](=[O:12])[CH2:10][N:1]2[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=[CH:2]2)[CH:14]=1)(=[O:29])=[O:30])=[O:57])[CH2:60][CH2:61][CH3:62]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 7519AnisoleHCID 61140Butyl chloroformate2×HCID 110190202-(Pyrrolidin-1-yl)pyridine2×HCID 671328723-[3-(2-Benzoimidazol-1-ylacetyl)phenyl]-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide

Product 1

HCID 56965019N-Butyloxycarbonyl-3-[3-(2-benzoimidazol-1-ylacetyl)phenyl]-5-iso-butyl-thiophene-2-sulfonamideYield 36%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 3-[3-(2-benzoimidazol-1-ylacetyl)phenyl]-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (54.4 mg, 0.107 mmol; see step (b)) in TFA (3 mL) was added anisole (150 μL) and the reaction mixture was stirred for 28 h at ambient temperature. The reaction mixture was concentrated in vacuo and dried in vacuo overnight. To the crude product dissolved in pyridine (1.5 mL) was added pyrrolidinopyridine (31.6 mg, 0.214 mmol) and butyl chloroformate (135.7 μL, 1.07 mmol), and the reaction mixture was stirred overnight. Another portion of pyrrolidinopyridine (31.6 mg, 0.214 mmol) and butyl chloroformate (135.7 μL, 1.07 mmol) was added and the reaction mixture was stirred overnight. Citric acid (10 mL, 10% aq) was added to the reaction mixture, which was then extracted with EtOAc, dried (over anhydrous MgSO4), concentrated in vacuo, and the residue purified by flash chromatography using MeOH:CH2Cl2 (5:95) as eluent to give the title compound in 36% yield, over two steps, (21 mg, 0.038 mmol).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customdried in vacuo overnight
  3. dissolutionTo the crude product dissolved in pyridine (1.5 mL)
  4. stirringthe reaction mixture was stirred overnight
  5. stirringthe reaction mixture was stirred overnight
  6. extractionwas then extracted with EtOAc
  7. dry with materialdried (over anhydrous MgSO4)
  8. concentrationconcentrated in vacuo
  9. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-59bc93e4eca94d45a5f25bdfa77b52e0
Source dataset
uspto-grants-2011_12
Patent number
US08080571B2

Reaction notes

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