Tetrahydrofuran → HCID 57932934, compound

Participants

Reaction Conditions

Reaction Steps

To a −78° C. solution of 1-methyl-1,2,4-triazole (0.15 mL, 2.04 mmol) and THF (3 mL) is added a 1.34 M solution of n-Bu-Li in hexanes (1.60 mL, 2.14 mmol) over 20 minutes, then stirred at −78° C. for 1.5 hours. A 0.5 M solution of ZnCl2 in THF (4.28 mL, 2.14 mmol) is added and the solution warmed to ambient temperature. 3-(5-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.40 g, 1.019 mmol) and PdCl2(dppf) (0.037 g, 0.051 mmol) is added and the solution heated at 65° C. overnight diluted with CH2Cl2 (30 mL). The organic layer is washed with 10% citric acid (20 mL), water (20 mL), brine (20 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO (20%-60% EtOAc/hexane gradient). The residue is dissolved in Et2O, treated with Darco®-60 for 15 minutes, dried with Na2SO4, and filtered to furnish the title compound (0.24 g, 0.61 mmol, 60%). 1H NMR (CDCl3), δ 0.88 (t, J=7.4 Hz, 6H), 1.75-1.93 (m, 4H), 2.20 (s, 3H), 2.50 (s, 3H), 2.51 (s, 3H), 3.28-3.37 (m, 1H), 4.14 (s, 3H), 6.69 (s, 1H), 7.45 (s, 1H), 7.87 (s, 1H). LC/MS (m/z): calcd. for C21H26N6S (M+H)+: 395.6; found: 395.2.

Provenance & Evidence