Method for the synthesis of rasagiline
We have developed a new method for the synthesis of Rasagiline (Formula 1) based on the alkylation of trifluoroacetyl protected aminoindan. This protection enabled us to carry out an alkylation of aminoindan with a high yield and purity under very mild conditions with a wide range of reaction conditions and reagent selection. Considering the ease, purity and high yields of introducing and removal of the trifluoroacetyl group, this approach is a highly practical and economical way for the synthesis of rasagiline or its pharmaceutically acceptable salts.
1. A compound of Formula 4 or a salt thereof,
2. A process for the preparation of a compound of Formula 1 or a salt thereof, said process comprising the steps of;
(a) alkylating a protected amide compound of Formula 3
with a compound of Formula 6 or an alkylating reagent that can be transformed into an alkyne,
in the presence of a base to obtain a compound of Formula 4
(b) hydrolyzing the compound of Formula 4 to obtain the compound of Formula 1 or a salt thereof.
3. The process according to the claim 2 , wherein the protected amide compound of Formula 3 is obtained by reacting a compound of Formula 2 with a trifluoroacetyl donating group
4. The process according to claim 2 , wherein the alkylating reagent used in the reaction is a compound of Formula 6.
5. The process according to claim 2 , wherein step (a) is carried out in the presence of a base selected from the group consisting of NaOtBu, KOtBu, Cs 2 CO 3 , and a mixture of Cs 2 CO 3 and K 2 CO 3 .
6. The process according to claim 2 , wherein step (a) is carried out in the presence of a phase transfer catalyst.
7. The process according to claim 6 , wherein the phase transfer catalyst is TBAI.
8. The process according to claim 2 , wherein step (a) is carried out in a solvent.
9. The process according to claim 8 , wherein the solvent is DMF or acetonitrile.
10. The process according to claim 2 , wherein step (b) is carried out in a solvent.
11. The process according to claim 2 , wherein step (b) is carried out with a base.
12. The process according to claim 2 , wherein the salt is a mesylate salt of Formula 1.
13. The process according to claim 2 , wherein said process is carried out in one pot.
14. The process according to claim 3 , wherein said process is carried out in one pot.
15. The process according to claim 2 , wherein said alkylating reagent that can be transformed into an alkyne is a compound of Formula 7 or Formula 8
16. The process according to claim 2 , further comprising step (c) converting the compound of the Formula 1 to its salt.
17. The compound of claim 1 wherein said compound is in a racemic mixture.