Trifluoroacetic acid → HCID 71625970, compound

Participants

Reaction Conditions

Reaction Steps

A pressure tube was charged with 6-chloro-4-(6-isopropyl-5-methylpyridin-2-ylamino) pyridazine-3-carboxamide (230 mg, 752 μmol), tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (242 mg, 1.13 mmol) and NMP (4 mL). The yellow solution was stirred at 130° C. for 2.5 days. After that, the NMP was distilled off using a Kugelrohr apparatus under high vacuum to afford a light brown solid. The crude solid was dissolved in dichloromethane and MeOH and adsorbed on silica gel, then purified by flash column (spherical silica 20-45 μm, 11 g, Versaflash from Supelco, eluting with 100% dichloromethane to 88:11.4:0.6 dichloromethane:methanol:NH4OH over 40 min) to give a light brown solid. The crude product was dissolved in dichloromethane (2 mL) and TFA (740 mg, 500 μL, 6.49 mmol) was added. The mixture was stirred at room temperature for 4 h. After that, the TFA and the dichloromethane were removed in vacuo, the brown solid obtained dissolved in dichloromethane, adsorbed on silica gel and then purified by flash column (spherical silica 20-45 μm, 11 g, Versaflash from Supelco, eluting with 100% dichloromethane to 88:11.4:0.6 dichloromethane:methanol:NH4OH over 40 min) to give 6-((1R,2S)-2-aminocyclohexylamino)-4-(6-isopropyl-5-methylpyridin-2-ylamino)pyridazine-3-carboxamide (70 mg, 24%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.65 (br. s., 1H), 8.37 (br. s., 1H), 7.92 (s, 1H), 7.61 (br. s., 1H), 7.48 (d, J=8.34 Hz, 1H), 6.71 (d, J=8.08 Hz, 1H), 6.66 (d, J=8.08 Hz, 1H), 3.24 (dt, J=13.39, 6.70 Hz, 1H), 3.08 (d, J=2.53 Hz, 1H), 2.26 (s, 3H), 1.30-1.75 (m, 11H), 1.26 (dd, J=6.70, 1.39 Hz, 6H). LC-MS 384 [M+H]+.

Provenance & Evidence