(R)-1-Boc-3-methylpiperazine → (R)-tert-Butyl 4-(5-(4-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-1-isopropyl-3-methyl-1H-indol-6-yl)pyridin-2-yl)-3-methylpiperazine-1-carboxylate

Participants

Reaction Steps

Added 6-(6-chloropyridin-3-yl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide (131 mg, 0.283 mmol), (R)-tert-butyl 3-methylpiperazine-1-carboxylate (70.8 mg, 0.354 mmol), sodium tert-butoxide (59.8 mg, 0.623 mmol) and 1,4-Dioxane (2 mL) to a microwave vial and degassed for 10 minutes. Added Pd XPhos (10.45 mg, 0.014 mmol) and heated to 100° C. for 16 hours. Concentrated, added DCM and water. Filtered, separated phases. Extracted aqueous phase twice more with DCM. Combined DCM extracts and washed with water, brine, dried (MgSO4), filtered and rotovapped off DCM. The residue was purified via Biotage (0% to 5% MeOH:DCM; 10 g-HP-silica gel column). Obtained 28 mg of the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.16 (d, J=6.32 Hz, 3 H), 1.44-1.57 (m, 15 H), 2.06 (s, 3 H), 2.28 (s, 3 H), 2.39 (s, 3 H), 2.87-3.36 (m, 3 H), 3.57 (s, 1 H), 3.86-4.30 (m, 3 H), 4.50 (d, J=9.35 Hz, 1 H), 4.58-4.79 (m, 3 H), 5.87 (s, 1 H), 6.64 (d, J=8.59 Hz, 1 H), 7.01 (s, 1 H), 7.45 (s, 1 H), 7.76 (d, J=8.08 Hz, 1 H), 8.46 (d, J=2.27 Hz, 1 H), 12.42 (br. s., 1 H). LCMS: [M+H]+ 627.5.

Provenance & Evidence