Process for preparing xanthine phosphodiesterase V inhibitors and precursors thereof

A method for producing a compound having the following formula:

• wherein,
• R1, R2 and R3 are each independently selected from the group consisting of:
• H, C1-15alkyl, C2-15alkenyl, C2-15alkynyl, C3-15cycloalkyl, aryl, heteroaryl, —OR5, —C(O)OR5, —C(O)R5, —C(O)N(R5)2, —NHC(O)R5 and —NHC(O)OR5, wherein R5 is H or C1-15alkyl;
• provided that R2 and R3 are not both —H;
• R4 is C1-12alkyl, C3-15cycloalkyl, C3-15cycloalkenyl, heterocycloalkyl, aryl or heteroaryl;
• wherein R1, R2, R3 and R4 are optionally substituted with one or more moieties independently selected from the group consisting of:
• C1-15alkyl, C3-15cycloalkyl, C2-15alkenyl, C3-15cycloalkenyl, C2-15alkynyl, aryl, heteroaryl, heterocycloalkyl, halo, nitro, oximino, acetate, propionate, pivaloyl, —OC(O)R5, —NC(O)R5 or —SC(O)R5, —OR50, —NR50R51, —C(O)OR50, —C(O)R50, —SO0-2R50, —SO2NR50R51, NR52SO2R50, ═C(R50R51), ═NOR50, ═NCN, ═C(halo)2—C(O)N(R50R51), —OC(O)R50, —OC(O)N(R50R51), —N(R52)C(O)(R50), —(R52)C(O)OR50 and —(R52)C(O)N(R50R51), wherein R5 is H or C1-12 alkyl and wherein R50, R51 and R52 are each independently selected from the group consisting of:
• H, Cf1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocycloalkyl, heteroaryl, and aryl;
• Hal is a halogen atom;
• the method comprising:
• a) forming a dihalogenated Compound 7 from compound 6:
• wherein Hal is selected to be the same halogen moiety for each occurrence;
• and
• b) reacting a Compound 7 with Compound 8, R4NH2, and a base, to form a compound of structure 9:
• wherein,
• L is selected to be R3.