Reacción #42533

Ecuación de reacción

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

isoquinoline-7-carboxylic acid

N,N-diisopropyl ethylamine

HBTU

→

N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}isoquinoline-7-carboxamide

Rendimiento 17.8%

Disolventes

methylene chloride

methylene chloride

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added in one portion
2. 2
   Lavadowashed with saturated sodium bicarbonate, saturated sodium chloride
3. 3
   Secadodried (sodium sulfate)
4. 4
   Filtraciónfiltered
5. 5
   Concentraciónconcentrated under reduced pressure
6. 6
   OtroPurification by flash column chromatography (silica, 0-5% methanol/methylene chloride)

Procedimiento

To a stirred solution of isoquinoline-7-carboxylic acid (200 mg, 1.15 mmol) and N,N-diisopropyl ethylamine (1.20 mL, 6.88 mmol) in methylene chloride (14.0 mL) was added HBTU (438 mg, 1.15 mmol) and the reaction stirred for 0.5 h. (2R,3S)-3-Amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (470 mg, 1.15 mmol) was added in one portion and the reaction mixture was stirred under nitrogen for 18 h. The reaction mixture was then diluted with additional methylene chloride and washed with saturated sodium bicarbonate, saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 0-5% methanol/methylene chloride) gave N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}isoquinoline-7-carboxamide (100 mg) which was characterized as its bis-HCl salt: mp 142-143° C.; ESI MS m/z 490 [M+H]+

Fuente