Process for preparing guanine derivatives

Claim 2

A process for preparing a compound of the formula ##STR18## wherein Wa is ##STR19## wherein each B is independently hydrogen or a pharmaceutically acceptable counterion, which process comprises contacting a solution of a compound of the formula ##STR20## wherein R is benzoyl or a triphenylmethyl group and Wa is as defined above with an acid or a base for a time sufficient to form compound of formula (I).

Claim 3

The process of claim 1 wherein R is benzoyl.

Claim 4

The process of claim 1 wherein R is a triphenylmethyl group.

Claim 5

The process of claim 2 wherein the solution of the compound of formula (XIV) is contacted with a base.

Claim 6

The process of claim 3 wherein the solution of the compound of formula (XIV) is contacted with an acid.

Claim 7

A process for preparing a compound of the formula ##STR21## wherein Wa is ##STR22## wherein each B is independently hydrogen or a pharmaceutically acceptable counterion and R is benzoyl which comprises (a) contacting a solution of a compound of the formula ##STR23## with t-butyldimethylsilyl chloride at -5° C. to room temperature for 1/2 to 4 hours to form a silyl-protected compound of the formula ##STR24## (b) contacting a solution of the compound formed in (a) with benzoyl chloride at -5° C. to 10° C. for 18 to 36 hours to form a compound of the formula ##STR25## wherein R is benzoyl; (c) removing the silyl protecting group from the compound formed in (b) by treating compound of formula (XII) with an acid at 50° C. to 100° C. for 1 to 6 hours to form a compound of the formula ##STR26## wherein R is benzoyl; and (d) contacting a solution of the compound formed in (c) with a phosphorylating agent at -5° C. to 10° C. for 1 to 4 hours to form a compound of formula (XIV).

Claim 8

A process for preparing a compound of the formula ##STR21## wherein Wa is ##STR22## wherein each B is independently hydrogen or a pharmaceutically acceptable counterion and R is benzoyl which comprises (a) contacting a solution of a compound of the formula ##STR23## with t-butyldimethylsilyl chloride at -5° C. to room temperature for 1/2 to 4 hours to form a silyl-protected compound of the formula ##STR24## (b) contacting a solution of the compound formed in (a) with benzoyl chloride at -5° C. to 10° C. for 18 to 36 hours to form a compound of the formula ##STR25## wherein R is benzoyl; (c) removing the silyl protecting group from the compound formed in (b) by treating compound of formula (XII) with an acid at 50° C. to 100° C. for 1 to 6 hours to form a compound of the formula ##STR26## wherein R is benzoyl; and (d) contacting a solution of the compound formed in (c) with a phosphorylating agent at -5° C. to 10° C. for 1 to 4 hours to form a compound of formula (XIV).

Claim 9

The process of claim 6 wherein the phosphorylating agent in (d) is pyrophosphoryl chloride.

Claim 10

A process for preparing a compound of the formula ##STR27## wherein Wa is ##STR28## wherein each B is independently hydrogen or a pharmaceutically acceptable counterion, and R is a triphenylmethyl group which comprises (a) contacting a solution of a compound of the formula ##STR29## with a triphenylmethyl chloride at 25° C. to 60° C. for 1/2 to 4 hours to form a compound of the formula ##STR30## wherein R is a triphenylmethyl group; and (b) contacting a solution of the compound formed in (a) with a phosphorylating agent at 15° C. to 30° C. for 1 to 5 days to form a compound of formula (XIV).

Claim 11

A process for preparing a compound of the formula ##STR27## wherein Wa is ##STR28## wherein each B is independently hydrogen or a pharmaceutically acceptable counterion, and R is a triphenylmethyl group which comprises (a) contacting a solution of a compound of the formula ##STR29## with a triphenylmethyl chloride at 25° C. to 60° C. for 1/2 to 4 hours to form a compound of the formula ##STR30## wherein R is a triphenylmethyl group; and (b) contacting a solution of the compound formed in (a) with a phosphorylating agent at 15° C. to 30° C. for 1 to 5 days to form a compound of formula (XIV).

Claim 12

The process of claim 8 wherein the triphenylmethyl chloride is triphenylmethyl chloride or 4-methoxyphenyl(diphenyl)methyl chloride.

Claim 13

The process of claim 8 wherein the phosphorylating agent is cyanoethylphosphate.

Claim 14

A process for preparing a compound of the formula ##STR31## wherein W and Wa are each ##STR32## wherein each B is independently hydrogen or a pharmaceutically acceptable counterion, which process comprises contacting a solution of a compound of the formula ##STR33## with a phosphorylating agent at -5° C. to 10° C. for 1 to 4 hours

Claim 15

A process for preparing a compound of the formula ##STR31## wherein W and Wa are each ##STR32## wherein each B is independently hydrogen or a pharmaceutically acceptable counterion, which process comprises contacting a solution of a compound of the formula ##STR33## with a phosphorylating agent at -5° C. to 10° C. for 1 to 4 hours

Claim 16

The process of claim 11 wherein the phosphorylating agent is pyrophosphoryl chloride.

Claim 17

A process for preparing a compound of the formula ##STR34## wherein W together with Wa is ##STR35## wherein B is hydrogen or a pharmaceutically acceptable counterion which process comprises cyclizing a compound of the formula ##STR36## by heating a solution of compound of formula (XV) in the presence of a condensing agent wherein Y is a lipophilic amine for 1/2 to 4 hours.

Claim 18

A process for preparing a compound of the formula ##STR34## wherein W together with Wa is ##STR35## wherein B is hydrogen or a pharmaceutically acceptable counterion which process comprises cyclizing a compound of the formula ##STR36## by heating a solution of compound of formula (XV) in the presence of a condensing agent wherein Y is a lipophilic amine for 1/2 to 4 hours.

Claim 19

The process of claim 13 wherein the condensing agent is dicyclohexylcarbodiimide.

Claim 20

The process of claim 14 wherein the lipophilic amine is 4-morpholino-N,N'-dicyclohexylcarboxamidine.

Claim 21

A process for preparing a compound of the formula ##STR37## wherein W and Wa are each ##STR38## wherein each B is independently hydrogen or a pharmaceutically acceptable counterion and x is 1 or 2 which process comprises contacting a solution of a compound of the formula ##STR39## wherein Z is hydrogen or P(O)M(OH) and M is 4-morpholino with tributylammonium phosphate or tributylammonium pyrophosphate at 40° C. to 50° C. for 6 to 16 hours.

Claim 22

A process for preparing a compound of the formula ##STR37## wherein W and Wa are each ##STR38## wherein each B is independently hydrogen or a pharmaceutically acceptable counterion and x is 1 or 2 which process comprises contacting a solution of a compound of the formula ##STR39## wherein Z is hydrogen or P(O)M(OH) and M is 4-morpholino with tributylammonium phosphate or tributylammonium pyrophosphate at 40° C. to 50° C. for 6 to 16 hours.

Claim 23

The process of claim 16 wherein x is 1 and the phosphorphating agent in tributylammonium phosphate.

Claim 24

The process of claim 16 wherein x is 2 and the phosphorphating agent in tributylammonium pyrophosphate.