Diisopropylethylamine → HCID 24831022, compound

Participants

Reaction Steps

(Step 2-i) tert-Butyl (R)-1-(6-(3-chlorophenylamino)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethylcarbamate (50 mg, 0.13 mmol) was dissolved in 5 mL TFA:CH2Cl2 (1:1) and left standing for 20 min. The solvent was removed under reduced pressure and CH2Cl2 was added and removed 4 times to remove residual TFA. The amine was dissolved in 1 mL NMP and 3-isocyanatopyridine (20 mg, 0.17 mmol) was added followed by the addition of DIEA (0.086 mL, 0.5 mmol). The reaction mixture was microirradiated at 100° C. for 10 min, loaded onto a preparative reversed-phase HPLC column, and the column eluted with a H2O/CH3CN 0.1% TFA gradient. Fractions containing pure product were combined and concentrated, 6M HCl was added, and the resulting solution concentrated to give the product, 1-((R)-1-(6-(3-chlorophenylamino)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)-3-(pyridin-3-yl)urea, as the HCl salt (31 mg, 0.076 mmol, 58% yield): 1H NMR (500 MHz, DMSO-d6) 10.30 (s, 1H), 10.00 (s, 1H), 9.10 (d, J=2.2 Hz, 1H), 8.45 (d, J=5.4 Hz, 1H), 8.31 (dd, J=1.2, 8.7 Hz, 1H), 8.16 (d, J=9.8 Hz, 1H), 7.94-7.89 (m, 2H), 7.76 (dd, J=1.5, 8.2 Hz, 1H), 7.61 (d, J=7.8 Hz, 1H), 7.36 (t, J=8.1 Hz, 1H), 7.23 (d, J=9.9 Hz, 1H), 7.06 (dd, J=1.4, 8.0 Hz, 1H), 5.52 (t, J=7.3 Hz, 1H), 1.68 (d, J=7.0 Hz, 3H); MH+409.20.

Provenance & Evidence