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СПОСОБ ПОЛУЧЕНИЯ ПИРАЗИНОНОВОГО ИНГИБИТОРА ТРОМБИНА И ПРОМЕЖУТОЧНЫХ СОЕДИНЕНИЙ ДЛЯ ЕГО ПОЛУЧЕНИЯ
专利权人:
ДИАКРОН ФАРМАСЬЮТИКАЛЗ; ИНК. (US)
发明人:
РЭДДИ Регури Бучи (IN),САМПАТХКУМАР Уппарапалли (IN),САХУ Нилам (IN),РАО Джавваджи Карунакара (IN),РЭДДИ Гэйд Брахма (IN)
申请号:
RU2012118499/04
公开号:
RU2012118499A
申请日:
2010.11.02
申请国别(地区):
RU
年份:
2013
代理人:
摘要:
1. A process for preparing a compound of formula (I):where 2,2-difluoro-2- (2-pyridyl) ethylamine or a salt thereof (K2) is reacted with ethyl 3-chloropyrazin (1H) -2-one-1-acetate (K3) to give ethyl 3- ( 2,2-difluoro-2- (2-pyridyl) ethylamino) pyrazin (1H) -2-one-1 -acetate (K), which is chlorinated and then reacted with 2-aminomethyl-3-fluoropyridine or a salt thereof (K1) to give (Compound of formula (I)), characterized in that it comprises:recovery of 2-cyano-3-fluoropyridine using Raney nickel, optionally in the presence of an acid, to give 2-aminomethyl-3-fluoropyridine or a salt thereof (K1)reacting 2,2-difluoro-2-pyridin-2-iletanola 4-toluenesulfonyl chloride to give 2,2-difluoro-2-pyridin-2-yl-ethyl-4-methylbenzenesulfonate which was converted into the compound of formula (K2) and optionally, a compound of formula purification (I).2. A method according to claim 1, characterized in that said salt comprises one or more salts selected from hydrochloride, hydrobromide, benzenesulfonate, hydrate or solvate.3. The method of claim 1, wherein the acid used for the recovery of 2-cyano-3-fluoropyridine comprises acetic acid or trifluoroacetic acid.4. A method according to claim 1, characterized in that the cleaning compound of formula (I) is carried out using an organic solvent selected from the group consistingof ketone, alcohol, ester, ether, hydrocarbon, galogenirovaiiogo solvent or mixtures thereof.5. The method according to claim 4, characterized in that ketop is acetone or butanone.6. The method of claim 4, wherein the alcohol is selected from the group consisting of methanol, ethanol, n-propanol, isopropanol (IPA), n-butapola, tert-butanol, hexanol and isoamyl alcohol.7. The method of claim 4, wherein the ester is selected from the group consisting of ethyl acetate, methyl acetate and isopropyl acetate.8. The method of claim 4, wherein the ether is diisopropyl ether or methyl tert-butyl ether (MTBE).9. The method of claim 4, wherein said hydrocarbon is selecte
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