Processes for the preparation of edoxaban and intermediates thereof
The present invention provides processes for the preparation of Edoxaban (1) and salts thereof, as well as intermediates thereof. In particular, intermediate compounds and/or salts of the Formulae (3), (4), (6-A), (7-A), (8-A), (9-A) and (10-AS) are provided.
1. A compound of Formula (9-A):
wherein
R 2 is selected from the group consisting of an aliphatic group, substituted aliphatic group, aryl, substituted aryl, arylalkyl, and substituted arylalkyl; wherein the aliphatic group is an alkyl group selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, t-butyl, sec-butyl, hexanyl, 2-methyl-2-hexanyl, cyclohexyl, 1-methylcyclohexyl, cyclopropylmethyl, and isomers of n-pentyl, n-hexyl, n-heptyl, and n-octyl; and
wherein substituted refers to the replacement of one or more hydrogen atoms with a substituent selected from the group consisting of R′″, OR″, NR″R″, SR″, halogen, SiR′″R′″R′″, OCOR′″, COR″, CO 2 R″, CONR″R″, NR″CO 2 R′″, NR″COR′″, SOR′″, SO 2 R′″, CN, NO 2 and CF 3 ;
R″ is selected, independently, from the group consisting of hydrogen, an aliphatic group, aryl and arylalkyl; and
R′″ is selected, independently, from the group consisting of an aliphatic group, aryl and arylalkyl.
2. The compound of claim 1 , wherein R 2 is an aliphatic group or a substituted aliphatic group.
3. The compound of claim 2 , selected from the group consisting of: