Process for preparing an A
View Patent ↗Disclosed is a synthesis suitable for large scale manufacture of an A 2A -adenosine receptor agonist, and also relates to polymorphs of that compound, and to methods of isolating a specific polymorph.
1. A monohydrate of (1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide, which monohydrate is in a crystalline form.
2. The monohydrate of claim 1 , wherein the crystalline form has a X-ray diffraction pattern as shown in FIG. 3 .
3. The monohydrate of claim 1 , wherein the crystalline form has a thermogravimetric analysis pattern and a differential scanning calorimetry pattern as shown in FIG. 2 .
4. The monohydrate of claim 1 , wherein the crystalline form is obtainable by a method comprising crystallizing (1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide in an aqueous protic solvent or an aqueous polar solvent.
5. The monohydrate of claim 1 , wherein the crystalline form is obtainable by a method comprising crystallizing (1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide in a solvent selected from a mixture of ethanol and water and a mixture of dimethylsulfoxide and water.
6. A method for preparing the monohydrate of claim 1 , comprising crystallizing (1-{9-[(4S,2R,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-methylcarboxamide in an aqueous protic solvent or an aqueous polar solvent.
7. The method of claim 6 , wherein the aqueous protic solvent or the aqueous polar solvent is selected from a mixture of ethanol and water and a mixture of dimethylsulfoxide and water.
8. The monohydrate of claim 1 , wherein the crystalline form has a 1 H NMR spectrum as shown in FIG. 1 .
9. The monohydrate of claim 1 , wherein the crystalline form is free of any impurity represented by the following structure: