STUK Timothy Lee (US),СТАК Тимоти Ли (US),BILLEN Denis (US),БИЛЛЕН Дэнис (US),WESTRICK Valerie Sue (US),ВЕСТРИК Валери Сью (US),GUNAWARDANA Vageesha Warnajith Liyana (US),ГУНАВАРДАНА Вагеша Варнаджит
申请号：
RU2018128023
公开号：
RU0002699034C1
申请日:
2017.02.07
申请国别(地区):
RU
年份:
2019
代理人:
摘要：
FIELD: chemistry.SUBSTANCE: invention relates to versions of an improved novel method of producing compound of 7H-pyrrolo[2,3-d]pyrimidine of formula 1 and a veterinarily acceptable salt thereof. Compound of formula 1 is a JAK inhibitor and can be used in treating diseases associated with JAK activity, such as cancer, asthma, etc. Method comprises a) reacting a compound – trans-4-((methylamino)cyclohexyl)methanesulphonic acid – with 4-substituted 7H-pyrrolo[2,3-d]pyrimidine in water in the presence of a base which is potassium carbonate, lithium, sodium or cesium, at reaction temperature from 60 to 105° with obtaining corresponding salt of trans-4-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclohexyl)methanesulphonic acid； b) converting the sulphonate salt obtained in step (a) into an intermediate compound which is trans-4-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclohexyl)methanesulphonyl chloride, in an organic solvent； and c) converting the intermediate compound of sulphonyl chloride obtained in step (b) into a compound of formula 1 by reacting an intermediate compound of sulphonyl chloride with a cold aqueous solution of methylamine, and in case of conversion of compound of formula 1 into its veterinary acceptable salt, reacting compound of formula 1 with corresponding acid in water at 50–65 °C until solid substances have dissolved, crystallization of the product, its separation by filtration, washing and drying. Method variant includes a) reaction of the compound – trans-4-((methylamino)cyclohexyl)methanesulphonic acid with 4-chloro-7H-pyrrolo[2,3-d]pyrimidine and potassium carbonate in water at a temperature of approximately 98 °C for 12 hours to obtain a potassium salt of trans-4-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclohexyl)methanesulphonic acid, cooling of reagents to about 30 °C, separating solid substances by filtration, washing solid substances with methanol, and drying the solid sulphonate； b) converting the sulphonate obtained in st
