Process for the preparation of lasmiditan
The present invention relates to a process for the preparation of lasmiditan, a compound of formula I, or pharmaceutically acceptable salts thereof, the process comprising reacting a compound of formula IV with morpholine to obtain a compound of formula II, reacting the of formula III with a compound of formula IIA to obtain lasmiditan or salt thereof.
1. A process for lasmiditan, a compound of formula I, or pharmaceutically acceptable salts thereof,
the process comprising:
(a) reacting a compound of formula III with a compound of formula IIA,
wherein R is MgX, Li, ZnX, or Sn (C 1 -C 6 alkyl) 3 ; X is selected from the group consisting of Br, Cl, and I; to obtain lasmiditan, the compound of formula I; and
(b) optionally, converting lasmiditan, the compound of formula I, to a pharmaceutically acceptable salt.
2. The process of claim 1 , wherein in step (b), lasmiditan is converted to lasmiditan hemisuccinate.
3. The process of claim 1 , wherein the compound of formula III is prepared by a process comprising reacting a compound of formula IV,
with morpholine to obtain the compound of formula III.
4. The process of claim 3 , wherein the reaction of the compound of formula IV with morpholine is carried out in the presence of a coupling reagent.
5. The process of claim 4 , wherein the coupling reagent is selected from the group consisting of a carbodiimide, a 1-hydroxybenzotriazole based or 1-hydroxy-7-azabenzotriazole based phosphonium and uronium salt, sulfinyl halide and phosphorus halide.
6. The process of claim 3 , wherein the reaction of the compound of formula IV with morpholine is carried out in the presence of a base.
7. The process of claim 6 , wherein the base is selected from the group consisting of an organic base, an inorganic base and mixture thereof.
8. The process of claim 7 , wherein the organic base is selected from the group consisting of a trialkyl amine, a heterocyclic amine and an organilithium.
9. The process of claim 7 , wherein the inorganic base is selected from the group consisting of a metal alkoxide, a metal carbonate, a metal bicarbonate, a metal hydroxide, wherein the metal is selected from the group consisting of sodium, potassium, lithium, calcium, cesium and magnesium.
10. A compound of formula III,
11. A process for in the preparation of lasmiditan, the compound of formula I or pharmaceutically acceptable salts thereof,
the process comprising converting the compound of formula III to lasmiditan,