5,7-Dimethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

Uses

5,7-Dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylic Acid is used as a reactant in the synthetic preparation of noninhibitory small molecule chaperones of glucocerebrosidase.

Synthesis

General procedure for the synthesis of 5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylic acid from ethyl 5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylate: to a solution of 5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylic acid ethyl 5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylate (2.2g, 10.0mmol) in methanol (15mL), was added an aqueous sodium hydroxide solution (5.67 mL, 7.2 M) and the reaction mixture was heated to reflux at 80 °C for 5 hours. After the reaction was completed, it was cooled to room temperature and neutralized with 2M hydrochloric acid. After neutralization, a white solid precipitated from the solution, which was collected by filtration, washed sequentially with water and ether, and dried in vacuum to afford 5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylic acid as a white solid (1.3 g, 68% yield). The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 8.21 (s, 1H), 6.84 (s, 1H), 2.65 (s, 3H), 2.53 (s, 3H). Electrospray mass spectrometry (ES-MS) showed m/z 192.00 ([M+H]+).

References

[1] Monatshefte fur Chemie, 2016, vol. 147, # 12, p. 2221 - 2234
[2] Patent: WO2016/73895, 2016, A1. Location in patent: Paragraph 00220
[3] Patent: WO2012/78855, 2012, A1. Location in patent: Page/Page column 17
[4] Journal of Medicinal Chemistry, 2012, vol. 55, # 12, p. 5734 - 5748
[5] Journal of Heterocyclic Chemistry, 2018, vol. 55, # 1, p. 214 - 225