反应详情

温度

55 °C

Combine 4-fluoro-benzoyl chloride (127 mg, 0.80 mmol), 6-(4-dimethylamino-cyclohex-1-enyl)-pyridin-2-ylamine, isomer 2 (preparation 11, 145 mg, 0.67 mmol), triethylamine (81 mg, 0.80 mmol) and 1,4-dioxane (6 mL) and heat at 55° C. for 15 hr. Dilute the mixture with DCM, wash with 0.1N NaOH solution. Extract the aqueous layer twice with DCM. Combine the organic layers, dry over sodium sulfate, filter and concentrate to give a residue. Purify the residue by chromatography (silica gel, 5% 2M NH3/MeOH in DCM) to provide the free amine of the title compound as a slightly yellow oil (183 mg, 80%): MS (ES): m/z=340.1 (M+H)+; 1H NMR (CDCl3): δ 8.55 (s, br, 1H), 8.19 (d, 1H), 7.95 (m, 2H), 7.73 (t, 1H), 7.18 (m, 2H), 6.66 (m, 1H), 2.73 (m, 1H), 2.47 (m, 3H), 2.37 (s, 6H), 2.15 (m, 2H), 1.57 (m, 1H). Using a salt formation method similar to that in example 1 gives the hydrochloride salt: hydrochloride salt: Anal. cal'd for C20H22FN3O.1.5HCl0.5H2O: C, 59.59; H, 6.13; N, 10.42. Found: C, 59.71; H, 5.56; N, 10.31.

1. washwash with 0.1N NaOH solution
2. extractionExtract the aqueous layer twice with DCM
3. dry with materialdry over sodium sulfate
4. filtrationfilter
5. concentrationconcentrate
6. customto give a residue
7. customPurify the residue by chromatography (silica gel, 5% 2M NH3/MeOH in DCM)