反応 #59797

反応方程式

2-piperazinone

diisopropylethylamine

[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone

3-{4-[4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-propionitrile hydrochloride

Phosgene

→

4-{4-[4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazine-1-carbonyl}-piperazin-2-one

溶媒

—

amine

methylene chloride

methylene chloride

反応条件

後処理

1. 1
   温度cooled in an ice bath
2. 2
   その他The solvent was evaporated
3. 3
   その他The mixture was sonicated
4. 4
   workup.WAITto stand at ambient temperature overnight
5. 5
   洗浄washed with water
6. 6
   その他The organic portion was separated
7. 7
   その他evaporated
8. 8
   その他to give the crude urea
9. 9
   その他Purification of the crude urea by flash chromatography (silica gel)

実験手順

[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone (50 mg, 0.085 mmol, example 8A) was dissolved in methylene chloride (1 mL) and cooled in an ice bath. Phosgene (250 uL, 20% solution in toluene)) was added, and the mixture was stirred for 30 min. The solvent was evaporated and the residue was taken in methylene chloride. One third of this solution (0.028 mmol) was treated with 2-piperazinone (8.5 mg) and diisopropylethylamine (15 ul). The mixture was sonicated to aid in dissolving the amine and allowed to stand at ambient temperature overnight. It was diluted with methylene chloride and washed with water. The organic portion was separated and evaporated to give the crude urea. Purification of the crude urea by flash chromatography (silica gel) using ethyl acetate and hexanes gave 4-{4-[4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazine-1-carbonyl}-piperazin-2-one (9.0 mg). LR-MS: 718.4 [(M+H)+].

出典