Optimized scale up of 3-pyrimidinylpyrazolo[1,5-a]pyridine via Suzuki coupling; a general method of accessing a range of 3-(hetero)arylpyrazolo[1,5-a]pyridines

We have developed an improved synthesis of 3-(hetero)aryl pyrazolo[1,5-a]pyridines (such as 3-(2,5-dichloropyrimidin-4-yl)pyrazolo[1,5-a]pyridine (8)) via an optimized synthesis and Suzuki coupling of 3-pyrazolo[1,5-a]pyridine boronic ester 10. These conditions are applicable to both high throughput chemistry and large scale synthesis of these medicinally important compounds. The scope of this chemistry has been further extended to include the synthesis and coupling of a novel boronic ester, 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine (43).

Graphical abstractReagents and conditions: (i) iPrMgCl.LiCl, iPrOBPin, 5 °C, THF, 90%,(ii) Pd(Amphos)Cl2, 2M Na2CO3 (2.2eq), 1.2 equiv trichloropyrimidine, DME/water (4:1), 85 °C, 59%.Figure optionsDownload full-size imageDownload as PowerPoint slide