Diisopropylethylamine → N'-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-N'-isopropyl-hydrazine-carboxylic acid methyl ester

HRID 79867Notes

Reaction equation

HRID 79867 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[CH3:13][O:14][C:15]([NH:17][NH:18][CH:19]([CH3:21])[CH3:20])=[O:16].CCN(C(C)C)C(C)C.[Br:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[NH:42][C:41]([CH:43]3[CH2:47][CH2:46][CH2:45][NH:44]3)=[N:40][CH:39]=2)=[CH:34][CH:33]=1>C(Cl)Cl>[CH3:13][O:14][C:15]([NH:17][N:18]([C:5]([N:44]1[CH2:45][CH2:46][CH2:47][CH:43]1[C:41]1[NH:42][C:38]([C:35]2[CH:36]=[CH:37][C:32]([Br:31])=[CH:33][CH:34]=2)=[CH:39][N:40]=1)=[O:11])[CH:19]([CH3:21])[CH3:20])=[O:16]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429Triphosgene2×HCID 436506945-(4-Bromo-phenyl)-2-pyrrolidin-2-yl-1H-imidazoleHCID 57863323Methyl 2-isopropylhydrazinecarboxylate

Product 1

HCID 66621058N'-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-N'-isopropyl-hydrazine-carboxylic acid methyl esterYield 33.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Triphosgene (1.05 g) was dissolved in DCM (17 mL) and stirred at 0° C. N′-Isopropyl-hydrazine-carboxylic acid methyl ester (1.00 g) and DIPEA (1.5 mL) were dissolved in DCM (25 mL), and mixture was added to triphosgene solution and stirred for 10 minutes. 5-(4-Bromo-phenyl)-2-pyrrolidin-2-yl-1H-imidazole (2.65 g) was added. Reaction was stirred at room temperature for 1 hour and extracted twice with water (10 mL), once with brine (10 mL), and evaporated under vacuum. The resulting oil was subjected to silica gel chromatography using a 40 g ISCO column and effluent of 0-100% ethyl acetate:hexanes. The fractions containing product were combined and the solvent was removed under vacuum, giving N′-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-N′-isopropyl-hydrazine-carboxylic acid methyl ester (533 mg, 16%).

Workup

  1. stirringstirred for 10 minutes
  2. customReaction
  3. stirringwas stirred at room temperature for 1 hour
  4. extractionextracted twice with water (10 mL), once with brine (10 mL)
  5. customevaporated under vacuum
  6. additionThe fractions containing product
  7. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-1c312cfcea424c209384ee2b6b297e54
Source dataset
uspto-grants-2014_09
Patent number
US08841278B2

Reaction notes

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