Reaktion #666055

Reaktionsgleichung

3-(trifluoromethyl)pyridine-2-carboxylic acid

HOBT hydrate

EDCI.HCl

3-trifluoromethyl-pyrazine-2-carboxylic acid

C-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropyl]-methylamine

→

3-trifluoromethyl-pyrazine-2-carboxylic acid [1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropylmethyl]-amide

Ausbeute 91.3%

Lösungsmittel

water

triethylamine

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe phases were separated
2. 2
   Extraktionthe aqueous phase was extracted with dichloromethane
3. 3
   Trocknendried with anhydrous sodium sulphate
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated
6. 6
   SonstigeCrude material was obtained as a yellow sticky solid, which
7. 7
   Sonstigewas purified by flash chromatography on silica gel with cyclohexane/ethyl acetate (1:1) as a solvent

Vorschrift

50 mg of C-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropyl]-methylamine (step 1 of PREPARATION EXAMPLE 2) was dissolved in 0.9 ml of dichloromethane and 0.085 ml of triethylamine was added at ambient temperature. Then 383 mg of 3-(trifluoromethyl)pyridine-2-carboxylic acid, 54 mg of HOBT hydrate, 76 mg of EDCI.HCl and 37 mg of 3-trifluoromethyl-pyrazine-2-carboxylic acid were added sequentially. The reaction mixture was stirred at ambient temperature for 14 hours and then water was added, the phases were separated and the aqueous phase was extracted with dichloromethane. The organic phases were combined, dried with anhydrous sodium sulphate, filtered and concentrated. Crude material was obtained as a yellow sticky solid, which was purified by flash chromatography on silica gel with cyclohexane/ethyl acetate (1:1) as a solvent. Thus, 76 mg of 3-trifluoromethyl-pyrazine-2-carboxylic acid [1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropylmethyl]-amide was obtained as a sticky solid. 1H-NMR (CDCl3): 8.80 ppm (s, 1H), 8.75 ppm (s, 1H), 8.65 ppm (s, 1H), 7.95 ppm (s, 1H), 7.70 ppm (m, 1H), 3.72 ppm (d, 2H), 1.18 ppm (m, 4H).

Quelle