Process for preparing xanthine phosphodiesterase V inhibitors and precursors thereof

1. A method for producing a compound of formula 13A:

the method comprising:

(i) reacting a compound of formula 7 with a primary amine Compound of Formula 8 or a hydrochloride salt thereof, in the presence of a base to form a compound of formula 9:

wherein L is a protecting group which is acetate, propionate, a pivaloyl protecting group, —OC(O)R 5 , or —NC(O)R 5 , wherein R 5 is H or C 1-12 alkyl and, wherein R 4 is alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl or heteroaryl, and R 4 is optionally substituted with one or more halo, nitro amino, or —C(O)OR 50 substituents, wherein —R 50 is H, Alkyl, cycloalkyl, heterocycloalkyl, heteroaryl or aryl; and

(ii) treating the compound of formula 9 with a base to remove the protecting group thereby forming a compound of Formula 13A

wherein Compound 7 is Compound 7A, Compound 8 is Compound 8A, Compound 9 is Compound 9A and the base in step (i) is sodium bicarbonate, and wherein the reaction is carried out in the presence of N,N-dimethyl acetamide as a solvent: according to the following scheme

wherein,

DMA is N,N-dimethyl acetamide

Me is CH 3 —; and

OAc is acetate.

2. The method of claim 1 wherein said compound of formula 7A is prepared by dihalogenating a compound of formula 6A in accordance with the reaction scheme:

wherein said reaction scheme comprises dibrominating Compound 6A using N-bromosuccinimide in acetonitrile as a solvent and sulfuric acid as a catalyst and wherein:

MeCN is acetonitrile:

NBS is N-bromosuccinimide,

Me is CH 3 —; and

QAc is acetate.

3. The method of claim 1 wherein the base in step (ii) is tetrabutylammonium hydroxide, the addition of which is followed by the addition of methanol:

wherein,

n-BU4NOH is tetrabutylammonium hydroxide;

Me is CH 3 —; and

OAc is acetate.