Process for making tetracyclic heterocycle compounds
View Patent ↗The present invention is directed to a process for making Tetracyclic Heterocycle Compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein X 1 , X 2 , R 1 , R 2 and R 3 are defined above herein. The present invention is also directed to compounds that may be useful as synthetic intermediates in the process of the invention.
1. A compound having the structure:
or a pharmaceutically acceptable salt thereof,
wherein:
X 1 and X 2 are each independently selected from Cl, Br, I, OTf, OTs, OMs or OBs;
R 1 represents up to 3 optional ring substituent groups, which can be the same or different and are selected from —C 1 -C 6 alkyl, halo, —OR 5 , —C(O)R 5 , —C(O) 2 R 5 , —NHC(O)R 5 , —C(O)N(R 5 ) 2 , —SR 5 , —C 1 -C 6 hydroxyalkyl, —C 1 -C 6 haloalkyl, —N(R 5 ) 2 , —S(O)R 5 , —S(O) 2 R 5 , —CN and —NO 2 ;
R 2 represents up to 3 optional ring substituent groups, which can be the same or different and are selected from —C 1 -C 6 alkyl, halo, —OR 5 , —C(O)R 5 , —C(O) 2 R 5 , —NHC(O)R 5 , —C(O)N(R 5 ) 2 , —SR 5 , —C 1 -C 6 hydroxyalkyl, —C 1 -C 6 haloalkyl, —N(R 5 ) 2 , —S(O)R 5 , —S(O) 2 R 5 , —CN and —NO 2 ;
R 3 is C 1 -C 6 alkyl, C 6 -C 10 aryl, 5 or 6-membered monocyclic heteroaryl or 9 or 10-membered bicyclic heteroaryl, wherein said C 6 -C 10 aryl group, said 5 or 6-membered monocyclic heteroaryl group and said 9 or 10-membered bicyclic heteroaryl group can each be optionally and independently substituted with up to 3 groups, each independently selected from C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, halo, —OR 5 , —C(O)R 5 ,—C(O) 2 R 5 , —NHC(O)R 5 , —C(O)N(R 5 ) 2 , —SR 5 , —C 1 -C 6 hydroxyalkyl, —C 1 -C 6 haloalkyl, —N(R 5 ) 2 , —S(O)R 5 , —S(O) 2 R 5 , —CN and —NO 2 ; and
R 4 is selected from Br, Cl, I, —OTf, —OMs, —OTs, —OBs, and —OS(O) 2 R 5 ; and
each occurrence of R 5 is independently selected from H, —C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl, 5 or 6-membered monocyclic heteroaryl and 9 or 10-membered bicyclic heteroaryl.
2. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof,
wherein:
R 2 represents an optional ring substituent group, which is —C 1 -C 6 alkyl or halo; and
R 3 is C 6 -C 10 aryl or 5 or 6-membered monocyclic heteroaryl wherein said C 6 -C 10 aryl group and said 5 or 6-membered monocyclic heteroaryl can each be optionally and independently substituted with C 1 -C 6 alkyl, halo or C 3 -C 7 cycloalkyl.
3. The compound of claim 1 , having the structure: