反应详情

2-Amino-6-(2-amino-ethylamino)-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide (25 mg, 65 μmol) described in Preparation Example A+-12, 4-fluoronitrobenzene (7.6 μl, 71 μmol) and N,N-diisopropylethylamine (22.7 μl, 130 μmol) were dissolved in dimethylsulfoxide (0.5 mL), the solution was stirred for 3.5 hours at room temperature, and then, the solution was stirred for 15.5 hours at 70° C. The reaction solution was cooled to room temperature, water was added, the solution was extracted with ethyl acetate, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, residue was purified by reverse phase high performance liquid chromatography (mobile phase:acetonitrile-water (containing 0.1% trifluoroacetic acid) was used), and the title compound (23 mg) was obtained as a trifluoroacetic acid salt.

1. stirringthe solution was stirred for 15.5 hours at 70° C
2. temperatureThe reaction solution was cooled to room temperature
3. extractionthe solution was extracted with ethyl acetate
4. washthe organic layer was washed with brine
5. dry with materialdried over anhydrous magnesium sulfate
6. customThe solvent was evaporated in vacuo, residue
7. customwas purified by reverse phase high performance liquid chromatography (mobile phase:acetonitrile-water (containing 0.1% trifluoroacetic acid) was used)