Imidazole → HCID 67176053, compound

HRID 572259Notes

Reaction equation

HRID 572259 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:9]2[C:20]2[CH:25]=[CH:24][C:23]([C:26](=[O:28])[NH2:27])=[CH:22][C:21]=2[CH3:29])=[CH:4][CH:3]=1.[NH:30]1[CH:34]=[CH:33][N:32]=[CH:31]1.N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.[Cu]I>[N:30]1([C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:9]3[C:20]3[CH:25]=[CH:24][C:23]([C:26](=[O:28])[NH2:27])=[CH:22][C:21]=3[CH3:29])=[CH:4][CH:3]=2)[CH:34]=[CH:33][N:32]=[CH:31]1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 58297378HCID 58297378, compound

Product 1

HCID 67176053HCID 67176053, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of ethyl 3-(1-(4-bromophenyl)-2-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-3-yl)propanoate (50 mg, 0.11 mmol), imidazole (68 mg, 10 mmol), L-proline (13 mg, 0.11 mmol), CuI (42 mg, 0.22 mmol), K2CO3 (76 mg, 0.55 mmol) and 4 Å molecular sieve (100 mg) in DMSO (3 mL) was heated at 130° C. for 24 h. After being cooled down to room temperature, the reaction mixture was filtered, and the filter cake was washed with ethyl acetate (10 mL×3). The combined filtrate was washed with saturated NaHCO3 aqueous solution (30 mL), and the aqueous layer was extracted with ethyl acetate (15 mL×3). The combined organic layers were washed with brine, dried over MgSO4, and concentrated. The residue was purified by preparative TLC (eluting with 7% methanol in dichloromethane) to give ethyl 3-(1-(4-(1H-imidazol-1-yl)phenyl)-2-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-3-yl)propanoate, (5-3, R1=1H-imidazol-1-yl) (25 mg, yield: 51%), which was used in the next step without further purification.

Workup

  1. temperatureAfter being cooled down to room temperature
  2. filtrationthe reaction mixture was filtered
  3. washthe filter cake was washed with ethyl acetate (10 mL×3)
  4. washThe combined filtrate was washed with saturated NaHCO3 aqueous solution (30 mL)
  5. extractionthe aqueous layer was extracted with ethyl acetate (15 mL×3)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified by preparative TLC (eluting with 7% methanol in dichloromethane)

Sources & evidence

ORD record
ord-2ab9ae367ff7405da4f714bdc292ebe9
Source dataset
uspto-grants-2015_05
Patent number
US09029402B2

Reaction notes

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