反应详情

Oxalyl chloride (0.049 ml, 0.55 mmol) was added slowly to a solution of 4-{3-[4-(3,3-dimethyl-butyl)-piperazin-1-yl]-3-oxo-propyl}-3-methyl-benzoic acid from Example E44 (100 mg, 0.28 mmol) in dichloromethane (10 ml) and few drops of DMF. The mixture was stirred for 1 h at room temperature then concentrated in vacuo and azeotroped with toluene. The residue was redissolved in dichloro-methane (10 ml) and DIEA (0.144 ml, 0.84 mmol) then 2-methyl-1,4,5,6-tetrahydro-1,3,6-triaza-benzo[e]azulene from Example E5 (55 mg, 0.28 mmol) was added. The mixture was stirred for 20 h at room temperature then washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloro-methane) to give a white fluffy solid identified as the title compound (42 mg, 28%).

1. concentrationthen concentrated in vacuo
2. customazeotroped with toluene
3. dissolutionThe residue was redissolved in dichloro-methane (10 ml)
4. stirringThe mixture was stirred for 20 h at room temperature
5. washthen washed with saturated NaHCO3
6. dry with materialbrine, dried
7. concentrationconcentrated in vacuo
8. customThe residue was purified by preparative HPLC (eluant; 0.5% 35% ammonia:9.5% methanol:90% dichloro-methane)
9. customto give a white fluffy solid