Preparation of purines
View Patent ↗A process for the preparation of a compound of formula (A) wherein: X is hydrogen, hydroxy, chloro, C 1-6 alkoxy or phenyl C 1-6 alkoxy; and R a and R b are hydrogen, or acyl or phosphate derivatives thereof, which process comprises: (i) the preparation of a compound of formula (I) whereiff R 1 is C 1-6 alkyl, or phenyl C 1-6 alkyl in which the phenyl group is optionally substituted; R 2 is hydrogen hydroxy, chlorine, C 1-6 alkoxy, phenyl C 1-6 alkoxy or amino; and R 3 is halogen, C 1-6 alkylthio, C 1-6 alkylsulphonyl, azido, an amino group or a protected amino group, which preparation comprises the reaction of a compound of formula (II), wherein R 2 and R 3 are as defined for formula (I) with a compound of formula (V) wherein L is a leaving group and R 1 is as defined for formula (I), to give a compound of formula (VI), and thereafter converting the intermediate compound of formula (VI) to a compound of formula (I) via decarboxylation, and, as necessary or desired, interconverting variables R 1 , R 2 and R 3 to further values of R 1 , R 2 and R 3 ; (ii) the conversion of the resulting compound of formula (I) to a compound of formula (A) by converting variable R 3 , when other than amino, to amino, reducing the ester groups CO 2 R 1 to CH 2 OH and optionally forming acyl or phosphate derivatives thereof, and as necessary or desired converting variable R 2 in the compound of formula (I) to variable X in the compound of formula (A); characterized in that R 2 is chloro in formula (I).
1. A process for the preparation of a compound of formula (A):
wherein
X is hydrogen or hydroxy; and R a and R b are hydrogen or acetyl, which process comprises:
(i) the preparation of a compound of formula (I):
wherein R 3 is an amino group or a protected amino group, which preparation comprises the reaction of a compound of formula (II):
wherein R 3 is as defined above for formula (I) with a compound of formula (V):
wherein L is a leaving group, to give a compound of formula (VI):
and thereafter converting the intermediate compound of formula (VI) to a compound of formula (I) via decarboxylation with sodium methoxide in methanol; and
(ii) conversion of the resulting compound of formula (I) to a compound of formula (A) by:
a) removal, if necessary, of the amino protecting group;
b) reducing the ester groups CO 2 Me to CH 2 OH groups, and, if necessary, acetylating to form the corresponding CH 2 OAc groups; and
c) dechlorinating via a hydrogenolysis reaction to yield a compound of Formula (A) in which X is hydrogen; or dechlorinating via a hydrolysis reaction to yield a compound of Formula (A) in which X is hydroxy.
2. A process for the preparation of a compound of formula (A):
wherein
X is hydrogen or hydroxy; and
R a and R b are hydrogen or acetyl, which process comprises:
(i) the preparation of a compound of formula (I):
wherein
R 1 is C 1-6 alkyl or phenylC 1-6 alkyl, in which the phenyl group is optionally substituted; and
R 3 is an amino group or a protected amino group, which preparation comprises the reaction of a compound of formula (I):
wherein R 3 is as defined above for formula (I), with a compound of formula (V):
wherein
L is a leaving group; and
R 1 is as defined above for formula (I), to give a compound of formula (VI):
and thereafter converting the intermediate compound of formula (VI) to a compound of formula (I) via decarboxylation; and
(ii) conversion of the resulting compound of formula (I) to a compound of formula (A) by:
a) removal, if necessary, of the amino protecting group;
b) reducing the ester groups CO 2 R 1 to CH 2 OH groups, and, if necessary, acetylating to form the corresponding CH 2 OAc groups; and
c) dechlorinating via a hydrogenolysis reaction to yield a compound of formula (A), in which X is hydrogen; or dechlorinating via a hydrolysis reaction to yield a compound of formula (A), in which X is hydroxy,
wherein decarboxylation of the compound of formula (VI) is effected by the addition of about 0.42 equivalents of sodium methoxide.