4-Methylmorpholine → (6S)-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',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-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) were added (6S)-2′-oxo-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxylic acid (19.1 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 (22 mg). HRMS 600.2347 (M+1). 1H NMR (400 MHz, DMSO): δ 11.13 (s, 1H); 9.39 (d, J=8.1 Hz, 1H); 8.91 (d, J=2.0 Hz, 1H); 8.15 (d, J=1.9 Hz, 1H); 8.10 (dd, J=5.3, 1.6 Hz, 1H); 7.48 (dd, J=7.3, 1.6 Hz, 1H); 7.42 (t, J=7.4 Hz, 2H); 7.38−7.29 (m, 3H); 6.94 (dd, J=7.3, 5.3 Hz, 1H); 5.49−5.40 (m, 1H); 4.70−4.62 (m, 1H); 3.72 (d, J=13.5 Hz, 1H); 3.50−3.32 (m, 4H); 2.62 (d, J=12.0 Hz, 1H); 2.36−2.28 (m, 1H); 174 (d, J=10.3 Hz, 1H); 1.64−1.52 (m, 2H); 1.27−1.20 (m, 1H); 1.18 (d, J=6.5 Hz, 3H).

Provenance & Evidence