Potassium Carbonate → (1-{2-[4-(4-ethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 2392341Notes

Reaction equation

HRID 2392341 reaction equation
COC(=O)N.C(=O)([O-])[O-].[K+].[K+].[CH3:12][O:13][C:14](=[O:44])[NH:15][CH:16]([C:20]([N:22]1[CH2:26][CH2:25][CH2:24][CH:23]1[C:27]1[NH:28][C:29]([C:32]2[CH:37]=[CH:36][C:35]([C:38]#[C:39][Si](C)(C)C)=[CH:34][CH:33]=2)=[CH:30][N:31]=1)=[O:21])[CH:17]([CH3:19])[CH3:18]>CO>[CH3:12][O:13][C:14](=[O:44])[NH:15][CH:16]([C:20]([N:22]1[CH2:26][CH2:25][CH2:24][CH:23]1[C:27]1[NH:28][C:29]([C:32]2[CH:37]=[CH:36][C:35]([C:38]#[CH:39])=[CH:34][CH:33]=2)=[CH:30][N:31]=1)=[O:21])[CH:17]([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 11722Methyl CarbamateHCID 66619941(2-methyl-1-{2-[5-(4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid methyl ester

Product 1

HCID 72338228(1-{2-[4-(4-ethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl esterYield 85.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of (1-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (364 mg, 0.81 mmol), Ethynyl-trimethyl-silane (0.68 mL, 4.9 mmol), Copper(I) iodide (154 mg, 0.81 mmol), tetrakis(triphenylphosphine)palladium (94 mg, 0.08 mmol) and triethylamine (0.67 mL, 4.9 mmol) in 5 ml DMF was heated to 70° C. overnight. The reaction mixture was cooled and dissolved in ethyl acetate and washed with 5% lithium chloride aqueous solution. The organic layer was dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexane) and followed by preparative reverse phase HPLC (GEMINI, 5 to 100% ACN/H2O+0.1% TFA) to give (2-Methyl-1-{2-[5-(4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid methyl ester (324 mg). LCMS-ESI−: calc'd for C25H34BN4O3Si: 466.65. Found: 467.1 (M+H+). (1-{2-[5-(4-Ethyny]-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester: Potassium carbonate (192 mg) was added to (2-Methyl-1-{2-[5-(4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-propyl)-carbamic acid methyl ester (324 mg) in 7 mL MeOH solution. The reaction was stirred at room temperature overnight. The reaction mixture was concentrated down and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexane) to give (1-{2-[5-(4-Ethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (234 mg).

Workup

  1. concentrationThe reaction mixture was concentrated down
  2. custompurified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-cf3384f5f8f243dc843505d944567325
Source dataset
uspto-grants-2012_09
Patent number
US08273341B2

Reaction notes

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