HUANG LIMING,BOEHM MARCUS F.,MOORJANI MANISHA,YEAGER ADAM RICHARD,MARTINBOROUGH ESTHER,BRAHMACHARY ENUGURTHI,TAMIYA JUNKO
申请号：
NZ59991310
公开号：
NZ599913A
申请日:
2010.11.15
申请国别(地区):
NZ
年份:
2014
代理人:
摘要：
Disclosed herein is a compound of formula I-R or I-S wherein the variables are defined in the specification the use thereof in the treatment of multiple sclerosis, transplant rejection, or acute respiratory distress syndrome by activation or agonism of a sphingosine-1-phosphate receptor subtype 1 and a method of preparing said compound comprising a chiral reduction of an oxo group bound to the sic-membered saturated ring of a tetrahydronaphthalene moiety with a ruthenium catalyst to form a compound of formaul VI-R or VI-S, functional group interconversion of the alcohol to an azide with diphenylphosphoryl azide to form a compound of formula VII-R or VII-S, when Z is &ndashCN, reacting the compound of formula VII-R or VII-S with a hydroxylamine or a hydroxylamine hydrochloride to forma a hydroxyamidine at the phenyl carbon to which Z is attached to form a compound of formula VIII-R or VIII-S followed by reaction with substituted benzoic acid and a coupling reagent to form a compound of formula IX-R or IX-S. In one embodiment the compound is 5-(3-(2-(hydroxymethyl)pyridin-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxy-benzonitrile.
