4-Methylmorpholine → 3-(2-Hydroxypropan-2-yl)-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1-(thiophen-3-yl)-1H-indazole-6-carboxamide

Participants

Reaction Conditions

Reaction Steps

3-(2-Hydroxypropan-2-yl)-1-(thiophen-3-yl)-1H-indazole-6-carboxylic acid (457.8 mg, 1.514 mmol), (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine bis-hydrochloride (374.3 mg, 1.871 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (600.2 mg, 3.13 mmol), 1-hydroxy-7-azabenzotriazole (105.3 mg, 0.774 mmol), and N-methylmorpholine (670 μl, 6.09 mmol) were dissolved in N,N-dimethylformamide (15 mL) 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 1 mL) and trifluoroacetic acid (ca 1 mL). The reaction mixture was purified directly by preparative HPLC (reverse phase (C-18)), eluting with acetonitrile/water 0.1% trifluoracetic acid, to give the title compound (559.5 mg, 1.360 mmol, 90% yield) as a white solid. FIRMS: [M+1]=412.1452. 1H NMR (400 MHz, CDCl3): δ 8.22 (s, 1H); 8.06 (d, J=8.5 Hz, 1H); 7.54 (dd, J=8.5, 1.4 Hz, 1H); 7.52-7.46 (m, 2H); 6.89 (d, J=7.7 Hz, 1H); 5.65-5.56 (m, 1H); 2.83 (s, 1H); 2.40 (s, 3H); 1.81 (s, 6H); 1.73 (d, J=7.1 Hz, 3H).

Provenance & Evidence