1,4-Dioxane → (5S)-5-amino-1-[6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]piperidin-2-one

Participants

Reaction Steps

A solution of tert-butyl N-[(3S)-1-[6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-6-oxo-3-piperidyl]carbamate (45 mg, 0.15 mmol) in hydrogen chloride (4 mol/l) in 1,4-dioxane (2.0 ml, 8.0 mmol) and 1,4-dioxane 2.0 mL was stirred at RT 18 h. The reaction was diluted with water then wash with EtOAc. The aqueous layer was basified with 1M NaOH to pH 10 and extracted with EtOAc. The organic layers was dried with sodium sulfate, filtered, and concentrated in vacuum. The crude product was submitted for reverse phase HPLC to give 202 (11 mg) in 18% yield. MS (ESI) m/z: 401.1. 1H NMR (400 MHz, DMSO) δ 9.61 (s, 1H), 9.47 (s, 1H), 9.35 (s, 1H), 8.73 (s, 1H), 8.63 (s, 1H), 8.04 (t, J=8.1 Hz, 1H), 7.83 (d, J=7.9 Hz, 1H), 7.76 (d, J=8.1 Hz, 1H), 4.24 (dd, J=12.2, 3.8 Hz, 1H), 3.94 (dd, J=12.3, 6.3 Hz, 1H), 3.49 (s, 1H), 2.75 (dd, J=12.2, 5.3 Hz, 1H), 2.69 (s, 3H), 2.63-2.55 (m, 1H), 2.10 (dd, J=13.0, 4.3 Hz, 1H), 1.85-1.72 (m, 1H).

Provenance & Evidence