Patent ID: 6576763
Filing Date: 2003-06-10
Classification: A61P,C07D,Y02P

Abstract:
A method for the preparation of a compound of Formula I, wherea) R1 is â€”C(O)CH(CH(CH3)2)NH2 or â€”C(O)CH(CH(CH3)CH2CH3)NH2 and R2 is â€”C(O)C3-C21 saturated or monounsaturated alkyl optionally substituted with up to five similar or different substituents independently selected from the group consisting of hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxy C1-C6 alkyl, C1-C6 alkanoyl, amino, halo, cyano, azido, oxo, mercapto and nitro; or b) R1 is â€”C(O)C3-C21 saturated or monounsaturated alkyl optionally substituted with up to five similar or different substituents independently selected from the group consisting of hydroxy, C1-C6 alkyl, C1-C6 alkoxy C1-C6 alkoxy C1-C6 alkyl C1-C6 alkanoyl, amino, halo, cyano, azido, oxo mercapto and nitro and R2 is â€”C(O)CH(CH(CH3)2)NH2 or â€”C(O)CH(CH3)CH2CH3)NH2; and R3 is OH or H; or a pharmaceutically acceptable salt thereof; the method comprising a) optionally protecting the purine 2 and/or 6 positions of a compound of formula I wherein R1 and R2 are each hydrogen; (b) regioselectively acylating or protecting the compound of Formula I at the side chain 4-hydroxy group with either i) an optionally N-protected valine or isoleucine group, ii) a saturated or monounsaturated C3-C21 COOH derivative which may be optionally substituted with up to five similar or different substituents independently selected from the group consisting of hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxy C1-C6 alkyl, C1-C6 alkanoyl amino, halo cyano azido, oxo, mercapto and nitro, or iii) a regioselective protecting group; c) acylating at the side chain 2-hydroxymethyl group with i) an optionally N-protected valine or isoleucine group, or ii) a saturated or monounsaturated C3-C21 COOH derivative which may be optionally substituted with up to five similar or different substituents independently selected from the group consisting of hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxy C1-C6 alkyl, C1-C6 alkanoyl, amino, halo, cyano, azido, oxo, mercapto and nitro; d) replacing the regioselective protecting group at R1, if present, with i) an optionally N-protected valine or isoleucine group; or ii) a saturated or monounsaturated C3-C21 COOH derivative which may be optionally substituted with up to five similar or different substituents independently selected from the group consisting of hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxy C1-C6 alkyl, C1-C6 alkanoyl amino halo cyano azido, oxo, mercapto and nitro; and e) deprotecting the resulting compound as necessary.