METHOD FOR PREPARING 5-¬4-(2-HYDROXY-ETHYL)-3,5-DIOXO-4,5-DIHYDRO-3H-¬1,2,4-TRIAZIN-2-YLBENZAMIDE DERIVATIVES WITH P2X7 INHIBITING ACTIVITY BY REACTION OF THE DERIVATIVE UNSUBSTITUTED IN 4-POSITION OF THE TRIAZINE WITH AN OXIRAN IN THE PRESENCE OF A LEWIS ACID

摘要

The present invention relates to methods of preparing compounds of formula I or a pharmaceutically acceptable salt thereof, wherein RSUP1/SUP, RSUP2/SUP, RSUP4/SUP, and RSUP7 /SUPhave any of the values as defined in the specification. The compounds are useful as agents in the treatment of diseases, including inflammatory diseases such as rheumatoid arthritis. Also provided are compositions of crystalline 2-Chloro-N-(1-hydroxy-cycloheptylmethyl)-5-[4-(2R-hydroxy-3-methoxy-propyl)-3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl]-benzamide comprising less than 2.5% residual organic solvent, and methods for preparing said compositions. Further provided are methods for crystallizing 2-Chloro-N-(1-hydroxy-cycloheptylmethyl)-5-[4-(2R-hydroxy-3-methoxy-propyl)-3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl]-benzamide.