4-Methylmorpholine → (2R)-N-{(5R,6S,8S)-5-Methyl-6-phenyl-3-[1-(trifluoromethyl)cyclopropyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl}-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide

Participants

Reaction Steps

To a solution of (5R,6S,8S)-5-methyl-6-phenyl-3-[1-(trifluoromethyl)cyclopropyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-amine (19.0 mg, 0.056 mmol) in N,N-dimethylformamide (565 μL) was added (2R)-2′-oxo-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridine]-5-carboxylic acid (19.0 mg, 0.68 mmol), 1-hydroxy-7-azabenzotriazole (0.77 mg, 5.7 μmol), N-methylmorpholine (14.9 μL, 0.136 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (13.0 mg, 0.068 mmol). The mixture was stirred 30 min. Water was added, and the mixture was purified by reverse phase chromatography (C-18, 95% water/acetonitrile→15% water/acetonitrile with 0.1% trifluoroacetic acid) giving the title compound (21 mg). HRMS 599.2367 (M+1). 1H NMR (400 MHz, DMSO): δ 11.12 (s, 1H); 9.19 (d, J=8.2 Hz, 1H); 8.08-8.05 (m, 1H); 7.85 (s, 1H); 7.82 (d, J=8.0 Hz, 1H); 7.41 (t, J=6.9 Hz, 3H); 7.36-7.27 (m, 3H); 7.23 (dd, J=7.3, 1.6 Hz, 1H); 6.89 (dd, J=7.3, 5.3 Hz, 1H); 5.43 (dt, J=10.7, 7.8 Hz, 1H); 4.69-4.61 (m, 1H); 3.70 (d, J=13.5 Hz, 1H); 3.43 (d, 16.3 Hz, 2H); 3.21 (d, J=16.3 Hz, 2H); 2.67-2.56 (m, 1H); 2.36-2.25 (m, 1H); 1.73 (d, J=10.3 Hz, 1H); 1.63-1.51 (m, 2H); 1.25 (d, J=9.3 Hz, 1H); 1.17 (t, J=6.5 Hz, 3H).

Provenance & Evidence