2-(Trimethylsilyl)ethanol → tert-Butyl 4-(5-(8-morpholino-2-(((2-(trimethylsilyl)ethoxy)carbonyl)amino)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Compound 20c (250 mg, 0.491 mmol) was placed in a 20 mL vial equipped with a stir bar and then DCM (4 mL) and DMF (10 μL) were added. Oxalyl chloride (100 μL, 1.15 mmol) was added dropwise via syringe and then the reaction was stirred for 20 min. The solvent was removed under reduced pressure. The residue was dissolved in DCM (25 mL) and then TMSN3 (100 μL, 0.760 mmol) was added. The reaction was stirred at rt for 16 h and then additional TMSN3 (100 μL, 0.760 mmol) was added. The reaction was stirred at rt for 24 h and then the solvent was removed under reduced pressure. The residue was dissolved in toluene (10 mL) and then 2-(trimethylsilyl)ethanol (1 mL, 7 mmol) was added. The flask was fitted with a reflux condenser and heated to 100° C. for 3 h. The reaction was cooled to rt and then the solvent was removed under reduced pressure. The residue was chromatographed on a 12 g SiO2 pre-packed column eluting with 0-80% ACN/DCM to afford compound 23a. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.51 (d, J=2.2 Hz, 1H), 7.99 (d, J=5.6 Hz, 1H), 7.90 (dd, J=8.9, 2.3 Hz, 1H), 6.73 (d, J=8.8 Hz, 1H), 6.70 (s, 1H), 6.09 (d, J=5.6 Hz, 1H), 4.10-4.20 (m, 2H), 3.84-3.96 (m, 8H), 3.50-3.62 (m, 8H), 1.49 (s, 9H), 0.00 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C30H44N8O5Si: 625.3 (M+H). Found: 625.3.

Provenance & Evidence