Isopropyl chloroformate → HCID 25122895, compound

Participants

Reaction Steps

To a solution of 4-(2-methylpyridin-3-yloxy)-1-(piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidine from Example 18A (44 mg, 0.14 mmol) in 2 mL of methylene chloride was added triethylamine (0.024 mL, 0.17 mmol) and isopropyl chloroformate (0.14 mL of a 1M solution in toluene, 0.14 mmol). The resulting mixture was allowed to stir at RT overnight. The mixture was diluted with ethyl acetate, washed with sat'd aq sodium bicarbonate and brine, dried (MgSO4), filtered through a pad of silica gel and concentrated in vacuo to an oil. The residue was purified by silica gel chromatography (12 g ISCO cartridge, 0-100% ethyl acetate/hexane, 15 min gradient) to afford isopropyl 4-(4-(2-methylpyridin-3-yloxy)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate free base (10 mg). Took up in 2 mL ether, added 2N hydrochloric acid (0.07 mL, 0.14 mmol), concentrated to a solid, triturated with hexane and dried in vacuo to afford 8 mg (14%) of Example 18 as an off-white solid. 1H NMR (500 MHz, CD3OD) δ ppm 1.28 (d, J=6.05 Hz, 6H) 2.00-2.06 (m, 2H) 2.16-2.25 (m, 2H) 2.64 (s, 3H) 3.05-3.16 (m, 2H) 4.26-4.33 (m, 2H) 4.90-4.94 (m, 1H) 5.06-5.13 (m, 1H) 7.94 (dd, J=8.25, 5.50 Hz, 1H) 8.36 (s, 1H) 8.47-8.50 (m, 2H) 8.69 (d, J=4.40 Hz, 1H). LRMS (ESI): 397.2 (M+H)+.

Provenance & Evidence