反应详情

温度

55 °C

Add 2,4,6-trifluorobenzoyl chloride (117 mg, 0.60 mmol) to a solution of 6-(4-dimethylamino-cyclohex-1-enyl)-pyridin-2-ylamine, isomer 1 (preparation 10, 100 mg, 0.46 mmol) in pyridine (6 mL) and heat at 55° C. overnight. Re-add another portion of 2,4,6-trifluorobenzoyl chloride (50 mg, 0.26 mmol) and heat at 65° C. for 4 hr. Remove volatiles under reduced pressure, dissolve the residue in 1N HCl, extract twice with ethyl ether. Adjust aqueous layer to pH>11 with 5N NaOH. Extract the aqueous layer there times with DCM. Combine 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 colorless oil (84 mg, 49%): MS (ion spray): m/z=376.2 (M+H)+; 1H NMR (CDCl3): δ 8.91 (s, br, 1H), 8.20 (d, 1H), 7.73 (t, 1H), 7.14 (d, 1H), 6.71 (m, 2H), 6.61 (m, 1H), 2.65 (m, 1H), 2.44 (m, 3H), 2.35 (s, 6H), 2.12 (m, 2H), 1.53 (m, 1H). Using a salt formation method similar to that in example 1 provides the di-hydrochloride salt. Di-hydrochloride salt: Anal. cal'd for C20H20F3N3O.2HCl: C, 53.58; H, 4.95; N, 9.37. Found: C, 53.42; H, 4.91; N, 9.23.

1. extractionextract twice with ethyl ether
2. extractionExtract the aqueous layer there times with DCM
3. dry with materialCombine organic layers, dry 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)