Stereoisomers and stereoisomeric mixtures of 1-(2,4-pyrimidinediamino)-2-cyclopentanecarboxamide synthetic intermediates
View Patent ↗The present invention provides stereoisomers and stereoisomeric mixtures of 1-(2,4-pyrimidinediamino), 2-formamido cyclopentyl intermediates useful for the preparation of compounds having antiproliferative activity and methods to prepare the intermediates.
1. A compound according to structural formula (I):
or a pharmaceutically acceptable salt or N-oxides thereof, wherein:
R 5 is halo, —CN, —NO 2 , CO 2 R a or —CF 3 ;
R a is selected from the group consisting of hydrogen, lower alkyl and lower cycloalkyl; and
LG is —S(O) 2 Me, —SMe,or a halide,
wherein the compound is enriched in one or more of the following stereoisomers according to structural formulae (II), (III) or (IV):
2. The compound of claim 1 in which R 5 is fluoro.
3. The compound of claim 1 in which R 5 is fluoro and LG is a halide.
4. A compound according to structural formula (II):
or a pharmaceutically acceptable salt or N-oxides therof, which is substantially free of the enantiomer and any diastereomers thereof, wherein R 5 and LG are as defined in claim 1 .
5. A compound according to structural formula (III):
or a pharmaceutically acceptable salt or N-oxides thereof, which is substantially free of the enantiomer and any diastereomers thereof wherein R 5 and LG are as defined in claim 1 .
6. A compound according to structural formula (IV):
or a pharmaceutically acceptable salt or N-oxides thereof, which is substantially free of the enantiomer and any diastereomers thereof wherein R 5 and LG are as defined in claim 1 .
7. The compound of any one of claims 4 - 6 in which R 5 is fluoro.
8. The compound of any one of claims 4 - 6 in which R 5 is fluoro and LG is a halide.
9. The compound of claim 1 in which a compound according to structural formula (I) is substantially free of a compound according to structural formula (V):
or a pharmaceutically acceptable salt or N-oxides thereof.
10. A compound according to structural formula (I) as defined in claim 9 which is enriched in one or more of the following stereoisomers according to structural formulae (II), (III) or (IV):
11. The compound of claim 9 or 10 in which R 5 is fluoro.
12. The compound of claims 9 or 10 in which R 5 is fluoro and LG is a halide.