Process for the synthesis of E1 activating enzyme inhibitors
The present invention provides processes and synthetic intermediate (Ia) for the synthesis of 4-substituted ((1S, 2S, 4R)-2-hydroxy-4-{7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)methyl sulfamates. These sulfamate compounds are E1 activating enzyme inhibitors, and are useful for the treatment of disorders of cell proliferation, particularly cancer, and other disorders associated with E1 activity.
1. A compound of formula (Ia):
or a salt thereof; wherein:
stereochemical configurations depicted at asterisk positions indicate absolute stereochemistry;
R a is hydrogen; or R a taken together with R j and the intervening atoms forms a cyclic diol protecting group;
R b is hydrogen;
R c is hydrogen;
R d is hydrogen;
R e is hydrogen;
R e′ is hydrogen;
each R f is independently hydrogen;
R g′ is chloro, bromo, fluoro, or iodo;
R h is hydrogen;
R h′ is hydrogen;
R j is hydrogen; or R j taken together with R a and the intervening atoms forms a cyclic diol protecting group;
R k is hydrogen.
2. The compound of claim 1 , wherein the compound is:
3. The compound of claim 1 , wherein each of R a and R j is hydrogen.
4. The compound of claim 3 , wherein R g′ is chloro, bromo, or iodo.
5. The compound of claim 4 , wherein R g′ is chloro or bromo.
6. The compound of claim 1 , wherein R g′ is chloro, bromo, fluoro, or iodo.
7. The compound of claim 6 , wherein R g′ is chloro or bromo.