3-(Azidomethyl)-6-(2,6-difluorophenyl)pyridazine → N-(4-chloro-3-pyridinyl)-2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-amine

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Reaction Steps

N-(4-chloro-3-pyridinyl)-2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-amine PMe3 (0.62 mL of 1.0 M solution in THF, 0.62 mmol) was added dropwise to a solution of 3-(azidomethyl)-6-(2,6-difluorophenyl)pyridazine (Preparation I, 140 mg, 0.57 mmol) in THF (2.5 mL) at RT. The reaction turned purple and an evolution of gas was observed. It was stirred for 15 min at RT. A solution of 4-chloro-3-isothiocyanatopyridine (Preparation XXIV, 106 mg, 0.62 mmol) in THF (1 mL) was added. After 15 min at RT, the reaction was diluted with EtOAc (50 mL) and washed with H2O (10 mL). The aqueous phase was extracted with EtOAc (2×15 mL). The combined organic layers were washed with brine (15 mL), dried over anh. Na2SO4, filtered and concentrated. The crude material was purified by silica gel chromatography (0-3% MeOH in CH2Cl2) to provide N-(4-chloro-3-pyridinyl)-2-(2,6-difluorophenyl)-imidazo[1,5-b]pyridazin-7-amine (110 mg, 54% yield) as an orange crystalline solid. MS (ESI, pos. ion) m/z: 350.8 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 9.90 (s, 1 H), 8.17 (d, J=5.09 Hz, 1 H), 7.79 (d, J=9.59 Hz, 1 H), 7.64 (s, 1 H), 7.40-7.51 (m, 1 H), 7.37 (s, 1 H), 7.32 (d, J=5.09 Hz, 1 H), 7.07 (m, 2 H), 6.57 (dt, J=9.44, 1.64 Hz, 1 H).

Provenance & Evidence