1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid synthesis

Yield:956011-26-0 96%

Reaction Conditions:

Stage #1: ethyl 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylatewith water;sodium hydroxide in 1,4-dioxane at 20; for 2 h;
Stage #2: with hydrogenchloride in 1,4-dioxane;water;

Steps:

29A.a 1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid

Step a) 1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid 10.0 g of ethyl 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylate (33.41 mmol; prepared according to WO 03/095451, Example 2A) are dissolved in 500 ml of dioxane/water (1:1), and 50 ml of 1 N aqueous sodium hydroxide solution (50 mmol) are added. The reaction mixture is stirred at room temperature for 2 h and then acidified with 1 N hydrochloric acid, whereupon the product precipitates out. The product is filtered off and dried under high vacuum. This gives 8.71 g (96% of theory) of the title compound. ¹H-NMR (400 MHz, DMSO-d₆): δ=5.84 (s, 2H), 7.14-7.18 (m, 1H), 7.21-7.26 (m, 2H), 7.35-7.41 (m, 1H), 7.45 (dd, J=8.1, 4.6 Hz, 1H), 8.49 (dd, J=8.1, 1.5 Hz, 1H), 8.69 (dd, J=4.4, 1.2 Hz, 1H), 13.40 (br. s, 1H).

References:

US2010/4235,2010,A1 Location in patent:Page/Page column 27