Process for preparing beta 3 agonists and intermediates
The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of I-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KED) biocatalyst enzymes and methods of using the biocatalysts.
1. A process of making compound I-7:
the process comprising mixing compound I-6:
with compound A-2:
in the presence of a solvent, adding an acid at a temperature below about 25° C.; and adding a coupling agent while maintaining a temperature below about 15° C.
2. The process of claim 1 , further comprising adding pyridine HCl to the mixture prior to adding the acid.
3. The process of claim 1 , wherein the coupling agent comprises CDI, DCC, EDC, EDC methiodide, T3P, HATU, HBTU, or mix-anhydrides.
4. The process of claim 3 , wherein the coupling agent comprises EDC.
5. The process of claim 1 , wherein the acid comprises HCl, HBr, HI, HNO 3 , MeSO 3 H, H 3 PO 4 , TFA, or H 2 SO 4 .
6. The process of claim 5 , wherein the acid is HCl.
7. The process of claim 1 , wherein the solvent comprises MeOH, EtOH, IPA, n-PrOH, MeCN, DMF, DMAc, NMP, THF, EtOAc, IPAc, or toluene.
8. The process of claim 1 , wherein the solvent is an aqueous solvent.
9. The process of claim 1 , wherein the solvent is IPA.
10. The process of claim 1 , wherein the process further comprises adding aqueous ammonia to the reaction mixture to form a slurry.
11. The process of claim 10 , wherein the process further comprises aging the slurry before filtration.