Methods for the preparation of 9-deazapurine derivatives

1. A method for the preparation of the β isomer of a 9-deazapurine derivative, which comprises forming a 9-deazapurine base on a 2-C-methyl-ribose protected with protecting groups at the 2- and 3-hydroxyl groups, and removing the protecting groups, wherein the protecting groups are benzyl groups, which comprises the step of preparing a compound of formula (2-4):

in which Bn represents a benzyl protecting group, and R represents a methyl group from a compound of formula (1-3):

in which Bn represents a benzyl protecting group, and R represents a methyl group.

2. The method of claim 1 , wherein the compound of formula (1-3) has been obtained by benzylation of 2-C-methylribonolactone using benzyl bromide and sodium hydride as a base.

3. The method of claim 1 or 2 , in which the β isomer of the 9-deazapurine derivative is selected from:

(2S,3R,4R,5R)-2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3,4-diol;

7-((2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-2-yl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-2-yl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(2S,3R,4R,5R)-2-(4-aminothieno[3,2-d]pyrimidin-7-yl)-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3,4-diol;

7-((2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-2-yl)thieno[3,2-d]pyrimidin-4(3H)-one;

2-amino-7-((2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-2-yl)thieno[3,2-d]pyrimidin-4(3H)-one;

(2S,3R,4R,5R)-2-(4-aminofuro[3,2-d]pyrimidin-7-yl)-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3,4-diol;

7-((2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-2-yl)furo[3,2-d]pyrimidin-4(3H)-one;

2-amino-7-((2S,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-2-yl)furo[3,2-d]pyrimidin-4(3H)-one;

(2S,3R,4R,5R)-2-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3,4-diol;

and pharmaceutically acceptable salts thereof.

4. The method of claim 3 , in which the β isomer 9-deazapurine derivative is (2S,3R,4R,5R)-2-(4-aminofuro[3,2-d]pyrimidin-7-yl)-5-(hydroxymethyl)-3-methyl-tetrahydrofuran-3,4-diol, or a pharmaceutically acceptable salt thereof.

5. A compound of formula (2-4):

in which Bn represents a benzyl protecting group, and R represents a methyl group.

6. A compound of formula (6-3)

in which Bn represents a benzyl protecting group, and R represents a methyl group.