Tetrahydrofuran → 8-(1-Ethyl-propyl)-2,6-dimethyl-3-[3-methyl-4-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazine

温度

65 °C

To a flask containing 3-(4-bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (below) (0.25 g, 0.64 mmol) and PdCl2(dppf) (0.023 g, 0.032 mmol) is added a solution of 0.5 M 6-methyl-2-pyridylzinc bromide in THF (2.5 mL, 1.27 mmol). The solution is heated at 65° C. overnight, diluted with EtOAc (25 mL), washed with sat. NH4Cl (20 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO (15%-20% EtOAc gradient) and is chromatographed (50×250 C18 Symmetry column, 10-70% water: 0.1% TFA/ACN: 0.1% TFA gradient). The residue is dissolved in Et2O (20 mL), washed with sat. NaHCO3 (15 mL) dried over MgSO4, filtered and concentrated to furnish the title compound (0.066 g, 1.57 mmol, 31%). 1H NMR (CDCl3) δ 0.87 (t, J=7.5 Hz, 6H), 1.73-1.91 (m, 4H), 2.20 (s, 3H), 2.47 (s, 3H), 2.49 (s, 3H), 2.61 (s, 3H), 3.29-3.38 (m, 1H), 6.66 (s, 1H), 7.09 (d, J=7.5 Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.54 (dd, J=7.5, 7.8 Hz, 1H), 7.72 (s, 1H). LC/MS (m/z): calcd. for C24H28N4S (M+H)+: 405.2; found: 405.3.

1. washwashed with sat. NH4Cl (20 mL)
2. dry with materialdried over MgSO4
3. filtrationfiltered
4. concentrationconcentrated
5. customThe residue is purified by ISCO (15%-20% EtOAc gradient)
6. customis chromatographed (50×250 C18 Symmetry column, 10-70% water: 0.1% TFA/ACN: 0.1% TFA gradient)
7. dissolutionThe residue is dissolved in Et2O (20 mL)
8. washwashed with sat. NaHCO3 (15 mL)
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated

ORDレコード

ord-c5a0aedb812d48329e42998cc8ea8b1d

出典データセット

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07612067B2