Methanol → 4-[5-(2,3-Difluoro-phenyl)-imidazol-1-yl]-1H-pyrrole-2-carboxylic acid

HRID 2249511Notes

Reaction equation

HRID 2249511 reaction equation
C([O:3][C:4]([C:6]1[N:7](S(C)(=O)=O)[CH:8]=[C:9]([N:11]=[CH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=2[F:20])[CH:10]=1)=[O:5])C.CO.CC1C=CC(S([CH2:37][N+:38]#[C-:39])(=O)=O)=CC=1.C([O-])([O-])=O.[K+].[K+]>COCCOC>[F:20][C:14]1[C:15]([F:19])=[CH:16][CH:17]=[CH:18][C:13]=1[C:12]1[N:11]([C:9]2[CH:10]=[C:6]([C:4]([OH:3])=[O:5])[NH:7][CH:8]=2)[CH:39]=[N:38][CH:37]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 161915Tosylmethyl isocyanideHCID 692890854-[(2,3-Difluoro-benzylidene)-amino]-1-methanesulfonyl-1H-pyrrole-2-carboxylic acid ethyl ester

Product 1

HCID 692882964-[5-(2,3-Difluoro-phenyl)-imidazol-1-yl]-1H-pyrrole-2-carboxylic acidYield 12.3%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 4-[(2,3-difluoro-benzylidene)-amino]-1-methanesulfonyl-1H-pyrrole-2-carboxylic acid ethyl ester (500 mg, 1.40 mmol) in co-solvents of MeOH (10 mL) and DME (5 mL) was added TosMIC (410 mg, 2.10 mmol) and K2CO3 (390 mg, 2,82 mmol). The reaction mixture was heated under reflux for 2 hours and the solvents were removed by evaporation. The residue was treated with LiOH in THF/H2O at room temperature for 14 hours. After removal of the solvents by evaporation, the residue was acidified by 2N HCl solution. The crude product was then purified by HPLC to afford 50 mg desired product (12%). MS (ES−): m/e=288.0 (M−H); LC/Method A/2.45 min.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 2 hours
  3. customthe solvents were removed by evaporation
  4. additionThe residue was treated with LiOH in THF/H2O at room temperature for 14 hours
  5. customAfter removal of the solvents
  6. customby evaporation
  7. customThe crude product was then purified by HPLC

Sources & evidence

ORD record
ord-aaecfcdac6fa478996a3a60f8559ba1e
Source dataset
uspto-grants-2008_01
Patent number
US07314885B2

Reaction notes

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