반응 #804275

반응 방정식

4-(5-methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzoic acid

TBTU

N,N-diisopropylethylamine CH2Cl2

methyl-(tetrahydro-pyran-4-ylmethyl)-amine

→

N-methyl-4-(5-methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-N-(tetrahydro-pyran-4-ylmethyl)-benzamide

수율 49.2%

용매

DMF

DMF

반응 조건

후처리

1. 1
   workup.ADDITIONwas added
2. 2
   세척eluting with DMF (2× column volumes), MeOH (2× column volumes)
3. 3
   기타the solvent removed in vacuo
4. 4
   기타the crude product purified by reverse phase preparative HPLC-MS

실험 절차

To 4-(5-methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-benzoic acid (35 mg, 0.125 mmol), TBTU (40 mg, 0.125 mmol) was added 0.36M N,N-diisopropylethylamine/CH2Cl2 (0.35 mL, 0.125 mmol) and anhydrous DMF (0.9 mL). The reaction mixture was stirred at RT for 45 min after which time methyl-(tetrahydro-pyran-4-ylmethyl)-amine (19 mg, 0.15 mmol) in anhydrous DMF (0.45 mL) was added and the reaction mixture was stirred at RT overnight. The reaction mixture was passed through a Si—NH2 cartridge (1 g), eluting with DMF (2× column volumes), MeOH (2× column volumes) and the solvent removed in vacuo and the crude product purified by reverse phase preparative HPLC-MS to obtain N-methyl-4-(5-methyl-1-oxo-1,2-dihydro-isoquinolin-3-yl)-N-(tetrahydro-pyran-4-ylmethyl)-benzamide as a yellow foam (24 mg, 48%).

출처