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

HRID 659687Notes

Reaction equation

HRID 659687 reaction equation
Br[C:2]1[N:3]([CH2:7][C:8]2[CH:9]=[C:10]([C:14]3[CH:18]=[C:17]([CH2:19][CH:20]([CH3:22])[CH3:21])[S:16][C:15]=3[S:23]([NH:26]C(C)(C)C)(=[O:25])=[O:24])[CH:11]=[CH:12][CH:13]=2)[CH:4]=[CH:5][N:6]=1.C1(OC)C=CC=CC=1.N1(C2C=CC=CN=2)[CH2:43][CH2:42][CH2:41][CH2:40]1.[Cl:50]C(OCCCC)=O.C(O)(=O)CC(CC(O)=O)([C:62]([OH:64])=[O:63])O>C(O)(C(F)(F)F)=O>[CH2:40]([O:64][C:62]([NH:26][S:23]([C:15]1[S:16][C:17]([CH2:19][CH:20]([CH3:21])[CH3:22])=[CH:18][C:14]=1[C:10]1[CH:11]=[CH:12][CH:13]=[C:8]([CH2:7][N:3]2[CH:4]=[CH:5][N:6]=[C:2]2[Cl:50])[CH:9]=1)(=[O:24])=[O:25])=[O:63])[CH2:41][CH2:42][CH3:43]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 7519AnisoleHCID 61140Butyl chloroformateHCID 110190202-(Pyrrolidin-1-yl)pyridineHCID 671329713-[3-(2-bromoimidazol-1-ylmethyl)phenyl]-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide

Product 1

HCID 56964911N-Butyloxycarbonyl-3-[3-(2-chloroimidazol-1-ylmethyl)phenyl]-5-iso-butyl-thiophene-2-sulfonamideYield 57%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 3-[3-(2-bromoimidazol-1-ylmethyl)phenyl]-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (44.1 mg, 0.086 mmol; see step (b)) in TFA (3 mL) was added anisole (150 μL) and the reaction mixture was stirred overnight 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 (25.6 mg, 0.173 mmol) and butyl chloroformate (109.9 μL, 0.846 mmol) and the reaction mixture was stirred for 36 h. Citric acid (3 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 57% yield, over two steps, (25 mg, 0.049 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 for 36 h
  5. extractionwas then extracted with EtOAc
  6. dry with materialdried (over anhydrous MgSO4)
  7. concentrationconcentrated in vacuo
  8. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-c6456d65e9af4a6eaea292b86fe50fa9
Source dataset
uspto-grants-2011_12
Patent number
US08080571B2

Reaction notes

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