AU2023274224B2 — Process for preparing tapinarof

USPTO Abstract

#$%^&*AU2023274224B220250710.pdf##### ABSTRACT The present invention provides processes for the preparation of 3, 5-Dihydroxy-4-isopropyl- trans-stilbene or a salt or solvate thereof and novel intermediates used therein. In some embodiments the 3, 5-Dihydroxy-4-isopropyl-trans-stilbene is prepared from (E)-2-chloro-2- isopropyl-5-styrylcyclohexane-1,3-dione. Also disclosed are crystal forms of 3, 5-Dihydroxy- 4-isopropyl-trans-stilbene or a salt or solvate thereof and pharmaceutical compositions comprising same. See Fig. 1. ABSTRACT The present invention provides processes for the preparation of 3, 5-Dihydroxy-4-isopropyl- trans-stilbene or a salt or solvate thereof and novel intermediates used therein. In some embodiments the 3, 5-Dihydroxy-4-isopropyl-trans-stilbene is prepared from (E)-2-chloro-2- isopropyl-5-styrylcyclohexane-1,3-dione. Also disclosed are crystal forms of 3, 5-Dihydroxy- 4-isopropyl-trans-stilbene or a salt or solvate thereof and pharmaceutical compositions comprising same. See Fig. 1. 20 23 27 42 24 04 D ec 2 02 3 A B S T R A C T T h e p r e s e n t i n v e n t i o n p r o v i d e s p r o c e s s e s f o r t h e p r e p a r a t i o n o f 3 , 5 - D i h y d r o x y - 4 - i s o p r o p y l - 2 0 2 3 2 7 4 2 2 4 0 4 D e c 2 0 2 3 t r a n s - s t i l b e n e o r a s a l t o r s o l v a t e t h e r e o f a n d n o v e l i n t e r m e d i a t e s u s e d t h e r e i n . I n s o m e e m b o d i m e n t s t h e 3 , 5 - D i h y d r o x y - 4 - i s o p r o p y l - t r a n s - s t i l b e n e i s p r e p a r e d f r o m ( E ) - 2 - c h l o r o - 2 - i s o p r o p y l - 5 - s t y r y l c y c l o h e x a n e - 1 , 3 - d i o n e . A l s o d i s c l o s e d a r e c r y s t a l f o r m s o f 3 , 5 - D i h y d r o x y - 4 - i s o p r o p y l - t r a n s - s t i l b e n e o r a s a l t o r s o l v a t e t h e r e o f a n d p h a r m a c e u t i c a l c o m p o s i t i o n s c o m p r i s i n g s a m e . S e e F i g . 1 .