Process for preparing aficamten
Provided herein is a process for the preparation of (R)—N-(5-(5-ethyl-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazole-4-carboxamide, intermediates thereof, and salts of the foregoing.
1. A method of preparing a compound of Formula (1):
comprising:
(i) converting a compound of Formula (7)
to a compound of Formula (6)
by reacting the compound of Formula (7) with (R)-tert-butanesulfinamide;
(ii) converting the compound of Formula (6), to a compound of Formula (5)
by reacting the compound of Formula (6) with a reducing agent; and
(iii) converting the compound of Formula (5) to the compound of Formula (1).
2. The method of claim 1 , wherein reacting the compound of Formula (7) with (R)-tert-butanesulfinamide is performed in the presence of a Lewis acid.
3. The method of claim 1 , wherein reacting the compound of Formula (7) with (R)-tert-butanesulfinamide is performed in the presence of a water scavenger.
4. The method of claim 1 , wherein reacting the compound of Formula (7) with (R)-tert-butanesulfinamide is performed in the presence of titanium ethoxide.
5. The method of claim 1 , wherein reacting the compound of Formula (7) with (R)-tert-butanesulfinamide is performed in the presence of toluene at a temperature of between about 75° C. and about 85° C.
6. The method of claim 1 , wherein reacting the compound of Formula (6) with a reducing agent is performed in the presence of tetrahydrofuran at a temperature of between about −15° C. and about −5° C.
7. The method of claim 1 , wherein the reducing agent is sodium borohydride.
8. The method of claim 1 , wherein the compound of Formula (6) is used without work-up or purification.