Ammonium Chloride → 8-(1-Ethyl-propyl)-2,6-dimethyl-3-[1-methyl-5-(3-methyl-thiophen-2-yl)-1H-pyrrol-2-yl]-imidazo[1,2-b]pyridazine

Participants

Reaction Conditions

Reaction Steps

A THF slurry (5 mL) of 3-(5-bromo-1-methyl-1H-pyrrol-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (143 mg, 0.38 mmol) and PdCl2(dppf)-CH2Cl2 complex (Aldrich, 19 mg, 0.023 mmol) is treated with 3-methyl-2-thienyl zinc bromide (Aldrich, 0.5 M in THF, 3.8 mL, 1.9 mmol) then heated to 60° C. for 1 hr. The resulting mixture is poured into sat'd NH4Cl (25 mL) and extracted with diethyl ether (35 mL). The organic extract is washed with aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude product is purified by chromatography using hexane-ethyl acetate gradient (100% hexane to 15% ethyl acetate in hexane) to elute the product. The material is purified a second time by flash chromatography using hexane-ethyl acetate gradient (100% hexane to 12% ethyl acetate in hexane) to elute the product. Only the fractions containing pure desired product, as judged by MS analysis, are collected and give the title compound (82.6 mg, 55% yield) as an oil. ES-MS (m/z): calc'd for C23H28N4S: 392.20. found 393.1 (M+H)+. 1H NMR (400 mHz, CDCl3): δ 7.28 (d, J=5.3 Hz, 1H), 6.96 (d, J=4.8 Hz, 1H), 6.67 (br s, 1H), 6.39 (d, J=3.5 Hz, 1H), 6.37 (d, J=4.0 Hz, 1H), 3.35 (br s, 1H), 3.33, (s, 3H), 2.52 (s, 3H), 2.51 (s, 3H), 2.26 (s, 3H), 1.89-1.76 (m, 4H), 0.87 (t, J=7.5 Hz, 6H).

Provenance & Evidence