Hexane → 3-[5-(2,4-Dimethyl-thiazol-5-yl)-3-methyl-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

温度

-78 °C

To a −78° C. mixture of 2,4-dimethylthiazole (0.23 g, 2.04 mmol) and THF (3 mL) is added 1.6 M t-Bu-Li in hexane (1.30 mL, 2.09 mmol). The mixture is stirred at −78° C. for 15 minutes. 0.5 M ZnCl2 in THF (4.3 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, 1.02 mmol) and PdCl2(dppf) (0.037 g, 0.051 mmol) is added and mixture is stirred at 65° C. overnight, diluted with EtOAc (20 mL), washed with 10% citric acid (15 mL), water (15 mL), brine (15 mL), dried over MgSO4, filtered and concentrated. The residue is purified by silica gel chromatography (0%-15% EtOAc/hexane gradient) furnish the title compound (0.21 g, 0.49 mmol, 49%). 1H NMR (CDCl3), δ 0.87 (t, J=7.5 Hz, 6H), 1.73-1.91 (m, 4H), 2.14 (s, 3H), 2.49 (s, 3H), 2.52 (s, 3H), 2.57 (s, 3H), 2.66 (s, 3H), 3.28-3.38 (m, 1H), 6.68 (s, 1H), 7.00 (s, 1H). LC/MS (m/z): calcd. for C23H28N4S2 (M+H)+: 425.3; found: 425.2.

1. temperaturethe solution warmed to ambient temperature
2. stirringmixture is stirred at 65° C. overnight
3. washwashed with 10% citric acid (15 mL), water (15 mL), brine (15 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue is purified by silica gel chromatography (0%-15% EtOAc/hexane gradient)

ORDレコード

ord-4c5e27eaefd34671aa9ceaac4f1efac9

出典データセット

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07612067B2