Process for preparing a 2-alkynyl substituted 5-amino-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine

1. A process for preparing the compound having the structural Formula I:

comprising:

(i) preparing a compound of Formula II:

using a process comprising:

(a) treating a compound V with triethyl orthoformate to obtain imidate VI:

(b) condensing imidate VI with 2-butynoylhydrazine p-toluenensulfonate (VII) to obtain the adduct compound VIII:

(c) cyclizing and dehydrating compound VIII with N,O-bistrimethylsilyl acetamide to obtain the 2-propynyl-substituted compound IX:

and

(d) hydrolyzing compound IX to obtain compound II;

(ii) condensing compound II with compound III to obtain compound IV

(iii) cyclizing compound IV to obtain compound I; and

(iv) optionally purifying the product of step (iii).

2. The process of claim 1 wherein said compound of Formula III is provided to the process by:

(a) treating the acetophenone XII with hydroxylamine hydrochloride to obtain the corresponding oxime (XIII)

(b) cyclizing the oxime XIII to the benzisoxazole XIV

(c) converting the benzisoxazole XIV to an organozinc reagent and coupling it with a protected piperazine in the presence of a copper catalyst to obtain the compound XV,

and

(d) removing the protecting group on compound XV and converting it to the HCl salt.

3. The process of claim 1 wherein said compound of Formula III is provided to the process by reacting 5-amino-6-fluoro-3-methylbenzo[d]-isoxazole (X) with bis(2-chloroethyl)amine in the presence of a base to obtain the compound of Formula III:

4. The process of claim 3 further comprising isolating compound III from the reaction mixture by the addition of an anti-solvent.

5. A compound of Formula II:

or Formula IV: