* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
An aq. NaOH solution (1.0M, 23 mL) is added to a solution of the respective carboxylic ester derivative (11.3 mmol) in THF (12 mL) and MeOH (4.0 mL). The mixture is stirred for 16h, the organic volatiles are removed in vacuo and water (10 mL) is added. The mixture is cooled to 00C and made acidic (pH = 3-4) by addition of hydrochloric acid (1.0 M). The obtained precipitate is filtered off, washed with cold water and dried in vacuo to give the desired acid which is used without further purification.
With sodium hydroxide; water; In ethanol;
imidazo[2,1-6]thiazole-5-carboxylic acid which was synthesised by saponification of the corresponding ethyl ester derivative (W01995/029922) with NaOH in a mixture water/EtOH.
To a solution of imidazo[2,1-b]thiazole-5-carboxylic ethyl ester derivative (1 g) in a mixture of THF/MeOH (3/1) (7.5 mL) was added dropwise NaOH 1N (2 eq). The reaction mixture was stirred at rt for 20 h. The mixture was then concentrated in vacuo, the residue was diluted with water (2.5 mL) and cooled to 0 C. The pH was adjusted to 3-4 by addition of HCl 1N. The resulting white precipitate was filtered off and the solid was rinsed sparingly with cold water. After drying in vacuo, the desired imidazo[2,1-b]thiazole-carboxylic acid derivative was obtained as a white solid.
A.l.6.4 Synthesis of imidazo[2,l-6]thiazole-5-carboxylic acid derivatives (general procedure)To a solution of imidazo[2,l-delta]thiazole-5-carboxylic ethyl ester derivative (1 g) in a mixture of THF/MeOH (3/1) (7.5 mL) was added dropwise NaOH IN (2 eq). The reaction mixture was stirred at rt for 20 h. The mixture was then concentrated in vacuo, the residue was diluted with water (2.5 mL) and cooled to 00C. The pH was adjusted to 3-4 by addition of HCl IN. The resulting white precipitate was filtered off and the solid was rinsed sparingly with cold water. After drying in vacuo, the desired imidazo[2,l- deltajthiazole-carboxylic acid derivative was obtained as a white solid. Imidazo[2,l-b]thiazole-5-carboxylic acidReaction with imidazo[2,l-delta]thiazole-5-carboxylic ethyl ester LC-MS: tR = 0.39 min; [M+H]+ = 169. 6-Methyl-imidazo[2,l-b]thiazole-5-carboxylic acid is commercially available from Apollo Scientific as OR25897.