Process for preparing methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-B]pyridin-3-yl]pyrimidin-5-yl}methylcarbamate and its purification for use as pharmaceutically active compound

1. A process for preparing methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamate of the Formula I:

comprising:

cleaving 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)-phenyldiazenyl]pyrimidine-4,6-diamine of the Formula III:

by catalytic hydrogenation to form 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4,5,6-pyrimidinetriamine of the Formula VIII:

and isolating the 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4,5,6-pyrimidinetriamine of the Formula VIII so formed by precipitation from a C 1 -C 4 alcohol and/or water without intermediate formation of salts;

reacting 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4,5,6-pyrimidinetriamine of the Formula VIII:

in a pyridine-free process with

(a) methyl chloroformate of the formula (V):

or

(b) dimethyl dicarbonate of the Formula X:

to produce methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinylcarbamate of the Formula VI:

and

methylating methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinylcarbamate of the Formula VI by reacting with a methylating agent of the Formula Me-X to form crude methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamate of the Formula I, wherein Me-X is selected from the group consisting of methyl iodide, dimethyl sulphate, and methyl toluenesulphonate.

2. The process of claim 1 further comprising:

concentrating said crude methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamate of the Formula I to dryness and purifying by preparative chromatography (RP-HPLC).

3. The process of claim 1 , wherein the catalytic hydrogenation occurs in a solvent that is selected from the group consisting of N,N-Dimethylformamide (DMF), N,N-dimethylacetamide (DMA) and N-methyl-2-pyrrolidone (NMP).

4. The process of claim 1 , wherein after catalytic hydrogenation, 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4,5,6-pyrimidinetriamine of the Formula VIII is isolated in a process comprising: removing the catalyst by filtration, precipitating the remaining-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4,5,6-pyrimidinetriamine of the Formula VIII with a C 1 -C 4 alcohol and/or water, and drying the precipitated 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4,5,6-pyrimidinetriamine of the Formula VIII.

5. The process of claim 4 , further comprising removing about 40-70% of the solvent by a partial distillative removal prior to precipitating the remaining 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4,5,6-pyrimidinetriamine of the Formula VIII with a C 1 -C 4 alcohol and/or water.

6. The process of claim 1 , wherein 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4,5,6-pyrimidinetriamine of the Formula VIII is reacted with methyl chloroformate of the formula (V).

7. The process of claim 1 , wherein 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4,5,6-pyrimidinetriamine of the Formula VIII is reacted with methyl chloroformate of the formula (V), a base is added, and methyl 4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinylcarbamate of the Formula VI is isolated by filtration.

8. The process of claim 7 , wherein the base is a trialkylamine having straight-chain, cyclic or branched C 1 -C 20 -alkyl radicals.

9. The process of claim 1 , wherein cleaving 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)-phenyldiazenyl]pyrimidine-4,6-diamine of the Formula III occurs in the presence of a Pd/carbon catalyst.