Syntheses of quinazolinones

A method for the synthesis of an enantiomerically pure compound of Formula 107/203:

• where:
• R1 is hydrogen, alkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, substituted alkyl, substituted aryl, substituted alkylaryl, substituted heteroaryl or substituted alkylheteroaryl;
• R2 is alkyl, oxaalkyl, aryl, alkylaryl, heteroaryl, alkytheteroaryl, substituted alkyl, substituted aryl, substituted alkylaryl, substituted heteroaryl or substituted alkylheteroaryl,
• R5, R6, R7 and R8 are independently hydrogen, hydroxy, alkyl, alkoxy, halogen, fluoroalkyl, nitro, cyano, substituted alkyl, amino, alkylamino, dialkylamino, alkylsulfonyl, alkylsulfonamido, sulfonamidoalkyl, sulfonamidoaryl, alkylthio, carboxyalkyl, carboxamido, aminocarbonyl, aryl or heretoaryl;
• and
• X is hydrogen or a protecting group,
• said method comprising the steps of:
• A) contacting isobutyl chloroformate with an enantiomerically pure compound of Formula 101:
• B) contacting the product of step A with a compound of Formula 103:
• to yield a compound of Formula 104:
• C) converting the compound of Formula 104 to a compound of Formula 105;
• D) contacting the compound of Formula 105 with an amine of the formula R1NH2 to yield a compound of Formula 106
• and
• E) contacting the compound of Formula 106 with a cyclo-dehydration reagent chosen from lithium hydroxide monohydrate, HMDS, phosphorous oxychloride, oxalyl chloride, thionyl chloride, Brugess' reagent, Ph3P/l2, and Vilsmeier reagent to yield the compound of Formula 107/203.