4-Methylmorpholine → 2-(Chlorophenyl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1-(4-methylphenyl)-1H-indazole-5-carboxamide

Participants

Reaction Conditions

Reaction Steps

3-(2-Chlorophenyl)-1-(4-methylphenyl)-1H-indazole-5-carboxylic acid (30.6 mg, 0.046 mmol, with 4 equivalents of sodium chloride), (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine bis-hydrochloride (13.72 mg, 0.069 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (17.52 mg, 0.091 mmol), 1-hydroxy-7-azabenzotriazole (3.11 mg, 0.023 mmol), and N-methylmorpholine (20.10 μl, 0.1.83 mmol) were dissolved in N,N-dimethylformamide (457 μl) at 25° C. The reaction mixture was heated to 50° C. and allowed to stir for 10 min. The reaction was stopped, quenched by addition of water (ca 0.2 mL) and trifluoroacetic acid (ea 0.2 mL). The reaction mixture was purified directly by preparative HPLC (Reverse phase (C-18)), eluting with acetonitrile/water 0.1% trifluoroacetic acid, to give the title compound (16.2 mg, 0.023 mmol, 50.6% yield) as a white solid. HRMS [M+1]=472.1532. 1H NMR (400 MHz, CDCl3): δ 8.17 (s, 1H); 7.88 (dd, J=8.9, 1.7 Hz, 1H); 7.74 (d, J=8.9 Hz, 1H); 7.65-7.60 (m, 3H); 7.56-7.53 (m, 1H); 7.42-7.38 (m, 2H); 7.34 (d, J=8.1 Hz, 2H); 6.79 (d, J=7.7 Hz, 1H); 5.58 (t, J=7.3 Hz, 1H); 2.42 (s, 3H); 2.36 (s, 3H); 1.68 (d, J=7.1 Hz, 3H).

Provenance & Evidence