Reacción #42498

Ecuación de reacción

4-Butyl-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid

HATU

HOBt

diisopropylethylamine

(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

diisopropylethylamine

→

title compound

Rendimiento 17.9%

4-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3,4-dihydro-2H-1,4-benzoxazine-6-carboxamide

Rendimiento 17.9%

Disolventes

methylene chloride

methylene chloride

methylene chloride

Condiciones de reacción

Tratamiento posterior

1. 1
   Lavadowashed with 1 N hydrochloric acid (15 mL), saturated sodium bicarbonate (15 mL), and brine
2. 2
   Secadodried (magnesium sulfate)
3. 3
   Filtraciónfiltered
4. 4
   Concentraciónconcentrated under reduced pressure
5. 5
   OtroPurification by flash column chromatography (silica, 1:9 methanol/chloroform)

Procedimiento

A solution of 4-Butyl-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid (43 mg), HATU (104 mg), HOBt (37 mg), and diisopropylethylamine (47 μL) was stirred in methylene chloride (1.0 mL) for 15 min. A solution of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride (62 mg) and diisopropylethylamine (47 μL) in methylene chloride (1.0 mL) was added and the reaction mixture was stirred overnight. The mixture was diluted with methylene chloride, washed with 1 N hydrochloric acid (15 mL), saturated sodium bicarbonate (15 mL), and brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 methanol/chloroform) provided 15 mg of the title compound: APCI MS m/z 552 [M+H]+.

Fuente