Synthesis of 2-aralkyloxyadenosines, 2-alkoxyadenosines, and their analogs

A process for the preparation of a compound of the formula

• wherein
• R1 and R2 are independently selected from hydrogen, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C8cycloalkyl, C3-C8cycloalkenyl, C7-C12aralkyl, C6-C12aryl, 5-7 membered heteroaryl, 4-7 membered heterocycloalkyl, each of which is optionally substituted with 1 to 3 substituents independently selected from the group consisting of hydroxy, C, -C6alkyl, C1-C6alkoxy, amino, mono-(C1-C6alkyl)amino, di-(C1-C6alkyl)amino, halogen, hydroxy, cyano, nitro, carboxylate, carboxamide, sulfonate, and sulfonamide;
• or
• NR1R2 taken in combination forms a 4-7 membered heterocycloalkyl or a 5-7 membered heteroaryl group, each of which is optionally substituted with 1 to 3 substituents independently selected from the group consisting of hydroxy, C1-C6alkyl, C1-C6alkoxy, amino, mono-(C1-C6alkyl)amino, di-(C1-C6alkyl)amino, halogen, hydroxy, cyano, nitro, carboxylate, carboxamide, sulfonate, and sulfonamide;
• R3 is aryl, cycloalkyl or heteroaryl, each of which is optionally substituted with 1 to 3 substituents independently selected from the group consisting of hydroxy, C1-C6alkyl, C1-C6alkoxy, amino, mono-(C1-C6alkyl)amino, di-(C1-C6alkyl)amino, halogen, hydroxy, cyano, nitro, carboxylate, carboxamide, sulfonate, and sulfonamide;
• and
• n is an integer of 2 or 3;
• which method comprises:
• a) protecting the hydroxyl groups of a compound of the formula
• wherein R1 and R2 have a meaning as described for formula (I), and X represents halogen, mesylate, tosylate or triflate, to afford a compound of the formula
• wherein R1, R2 and X have a meaning as described above, and Bc, Bc′ and Bc″ represent, independently from each other, the same or a different hydroxyl protecting group;
• b) treating a resulting compound of formula (III) in the absence of an extrinsic solvent with an alcohol of the formula
• R3(CH2)nOH (IV)
• wherein R3 and n have a meaning as described for formula (I), and a strong base, to afford a compound of the formula
• wherein R1, R2, R3, Bc, Bc′, Bc″ and n have a meaning as described above;
• and
• c) deprotecting the hydroxyl groups of a resulting compound of formula (V) to afford a compound of formula (I) wherein R1, R2, R3 and n have a meaning as described above.