Reacción #42590

ord-1b15a28c605a476a99c8dcce01432d82

Ecuación de reacción

CN(C)C(On1nnc2cccnc21)=[N+](C)C.F[P-](F)(F)(F)(F)F
HATU
On1nnc2ccccc21
HOBt
CCN(C(C)C)C(C)C
diisopropylethylamine
Cl
hydrochloric acid
CCOCC
diethyl ether
Cl.Cl.Nc1c(F)c(N)c(F)c(F)c1F
dihydrochloride
CCc1cccc(CNC[C@@H](O)[C@@H](N)Cc2cc(F)cc(F)c2)c1
(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol
CCN(C(C)C)C(C)C
diisopropylethylamine
CCc1cccc(CNC[C@@H](O)[C@H](Cc2cc(F)cc(F)c2)NC(=O)c2cc(C)cc(-c3ncco3)c2)c1.Cl
title compound
CCc1cccc(CNC[C@@H](O)[C@H](Cc2cc(F)cc(F)c2)NC(=O)c2cc(C)cc(-c3ncco3)c2)c1.Cl
N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(1,3-oxazol-2-yl)benzamide hydrochloride

Condiciones de reacción

Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    Lavadowashed with 1 N hydrochloric acid (20 mL), saturated sodium bicarbonate (20 mL), and saturated sodium chloride
  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)
  6. 6
    Otroprovided a clear solid
  7. 7
    FiltraciónThe resulting precipitate was collected by filtration

Procedimiento

A solution of the acid from step 6 (358 mg, 1.8 mmol), HATU (1.0 g, 2.6 mmol), HOBt (357 mg, 2.6 mmol), and diisopropylethylamine (500 μL, 2.6 mmol) was stirred in methylene chloride (2.0 mL) for 15 min. A solution of dihydrochloride of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (718 mg, 1.8 mmol) and diisopropylethylamine (500 μL, 2.6 mmol) in methylene chloride (2.0 mL) was added and the reaction mixture was stirred overnight. The reaction mixture was diluted with methylene chloride, washed with 1 N hydrochloric acid (20 mL), saturated sodium bicarbonate (20 mL), and saturated sodium chloride, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 methanol/chloroform) provided a clear solid. The solid was dissolved in methanol (2 mL), and treated with hydrochloric acid (0.5 mL of a 1.0 M solution in diethyl ether, 0.5 mmol). The resulting precipitate was collected by filtration to provide the title compound (250 mg): mp 105-107° C.; APCI MS m/z 520 [M+H]+.

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US07727997B2uspto-grants-2010_06