반응 #159682

반응 방정식

methyl 4-(1-aminocyclopropyl)benzoate

methyl 4-(1-aminocyclopropyl)benzoate hydrochloride

triethylamine

2-(3-(3-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenoxy)azetidin-1-yl)-5-chloronicotinic acid

1-Hydroxybenzotriazole hydrate

1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride

→

tert-butyl 4-(3-((1-(5-chloro-3-((1-(4-(methoxycarbonyl)phenyl)cyclopropyl)carbamoyl)pyridin-2-yl)azetidin-3-yl)oxy)phenyl)piperazine-1-carboxylate

수율 66.6%

용매

Water

dimethylformamide

dimethylformamide

반응 조건

후처리

1. 1
   workup.STIRRINGthe resulting mixture was stirred 40 min at room temperature
2. 2
   여과the resulting precipitate was collected by filtration
3. 3
   기타purified by Biotage column (10 g)
4. 4
   세척eluting with a mixture dichloromethane/ethylacetate from 100/0 to 80/20
5. 5
   기타Collected fractions, after solvent evaporation

실험 절차

A suspension of 2-(3-(3-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenoxy)azetidin-1-yl)-5-chloronicotinic acid (D110) (150 mg, 0.306 mmol), 1-Hydroxybenzotriazole hydrate (47 mg, 0.306 mmol) and 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (88 mg, 0.46 mmol) in dimethylformamide (2 ml) was stirred 40 min at room temperature. A solution of methyl 4-(1-aminocyclopropyl)benzoate (D7) (68.9 mg, 0.306 mmol) and triethylamine (0.042 ml, 0.306 mmol) in dimethylformamide (2 ml) was added and the resulting mixture was stirred 40 min at room temperature. Water (2 ml) was added and the resulting precipitate was collected by filtration and purified by Biotage column (10 g) eluting with a mixture dichloromethane/ethylacetate from 100/0 to 80/20. Collected fractions, after solvent evaporation, afforded tert-butyl 4-(3-((1-(5-chloro-3-((1-(4-(methoxycarbonyl)phenyl)cyclopropyl)carbamoyl)pyridin-2-yl)azetidin-3-yl)oxy)phenyl)piperazine-1-carboxylate (135 mg)

출처