Sodium Hydroxide → 2-(4-Chloro-3-(trifluoromethyl)phenyl)-N-(2-(1,3-dihydroxypropan-2-yl)-1-oxo-1,2-dihydroisoquinolin-5-yl)acetamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-amino-2-(1,3-dihydroxypropan-2-yl)isoquinolin-1(2H)-one (100.0 mg, 0.0004055 mol) in N,N-dimethylformamide (8 mL, 0.1 mol) was added 2-(4-chloro-3-(trifluoromethyl)phenyl)acetic acid (378.0 mg, 0.001584 mol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (448.0 mg, 0.001178 mol) and N,N-diisopropylethylamine (600.0 μL, 0.003445 mol). The reaction mixture was stirred for 16 hours at 50° C. After most of the DMF was rotovaped, MeOH (20 mL) and 2N NaOH (5 mL) were added to the residue. The solution was stirred for 1 hour at room temperature. MeOH was rotovaped and EtOAc (100 mL) was added, and the resultant solution was then washed with water (2×100 mL), Sat. NaHCO3, H2O, and brine. The EtOAc layer was dried by MgSO4 and was rotovaped. The resultant solution was washed with DCM and then purified with silica-gel. The final product was obtained as a solid. MS m/z=455.1 (M+1). 1H NMR (400 MHz; DMSO-d6) δ 10.09(s, 1 H), 8.09(d, J=8.0 Hz, 1 H), 7.89(s, 1 H), 7.80(d, J=7.6 Hz, 1 H), 7.75-7.65(m, 2 H), 7.55-7.40(m, 2 H), 6.63(d, J=7.6 Hz, 1 H), 4.98-4.85(m, 3 H), 3.92(s, 2 H), 3.85-3.65 (m, 4 H).

Provenance & Evidence