Reaktion #159682

Reaktionsgleichung

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

Ausbeute 66.6%

Lösungsmittel

Water

dimethylformamide

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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)

Quelle