Regadenoson Impurity 3 synthesis

Yield:1423073-21-5 91%

Reaction Conditions:

Stage #1: 2-hydrazinoadenosinewith acetic acid in water; for 0.0833333 h;
Stage #2: 3,3-diethoxy-2-methoxycarbonylpropen-1-ol sodium salt in 1,2-dimethoxyethane;water at 55 - 60; for 3 h;

Steps:

4 Example 4

15 ml of acetic acid are added to a suspension of 8.8 g of 2-hydrazinoadenosine (29.6 mmol) in 40 ml of water.
After stirring at the laboratory temperature for ca. 5 mins, a solution is produced, to which a solution of 9.96 g of the sodium salt of 3,3-diethoxy-2-methoxycarbonylpropen-1-ol in 1,2-dimethoxyethane is added.
A yellow reaction solution is obtained, which is heated to 55 to 60° C. and maintained for 3 hours, while the product precipitates.
Then the thick reaction mixture is cooled and filtered.
After filtration and washing with water and methanol the product is dried to dryness in vacuo.
This procedure provides 10.9 g of 2-(4-methoxycarbonylpyrazol-1-yl)adenosine, i.e. 91.0%, with the purity of 98.0% (HPLC).

References:

US2014/206857,2014,A1 Location in patent:Paragraph 0041