反应详情

In a 2 dram reaction vial was added 6-chloro-8-(4-ethoxyphenylamino)imidazo[1,2-b]pyridazine-3-carbonitrile (0.055 g, 0.017 mmol) from 1c and trans-1,4-diaminocyclohexane (1.0 g, 8.0 mmol). The mixture was allowed to melt at 160° C. for 1.5 hrs. The melt was then cooled, diluted with water and extracted with dichloromethane. The organic layer was concentrated and then diluted with MeOH, and then purified by preparative HPLC to give 0.039 g of the title compound as a TFA salt. 1H NMR (500 MHz, Solvent) δ ppm 7.91 (1H, s), 7.23 (2H, d, J=8.80 Hz), 6.96 (2H, d, J=8.80 Hz), 5.96 (1H, s), 4.04 (4H, q, J=6.78 Hz), 3.61-3.80 (1H, m), 2.99-3.19 (1H, m), 2.16-2.35 (2H, m, J=11.55 Hz), 2.01-2.16 (2H, m, J=12.65 Hz), 1.47-1.65 (2H, m), 1.39 (3H, t, J=7.15 Hz), 1.24-1.36 (2H, m). LC/MS, m/e 392 (M+1). HPLC Rt, 2.69 min. YMC ODSC18 column (4.6×50 mm). 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

1. customIn a 2 dram reaction
2. temperatureThe melt was then cooled
3. extractionextracted with dichloromethane
4. concentrationThe organic layer was concentrated
5. additiondiluted with MeOH
6. custompurified by preparative HPLC