4-Aminopyridine → 8-Bromo-6-chloro-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

Temperatur

25 °C

To a 2 dram vial was added a mixture of 8-bromo-6-chloroimidazo[1,2-b]pyridazine-3-carboxylic acid and 6,8-dichloroimidazo[1,2-b]pyridazine-3-carboxylic acid (250 mg, 1.077 mmol), and oxalyl chloride (1.077 mL, 2.155 mmol) in dichloromethane (2 mL). The solution was stirred at 25° C. for 1 hour. The solvent and excess oxalyl chloride were removed in vacuo. The residue was dissolved in dichloromethane (2 mL), and triethylamine (0.451 mL, 3.23 mmol), pyridin-4-amine (152 mg, 1.616 mmol), and 2 crystals of DMAP were added. The reaction solution was stirred at 25° C. for 6 hours. The solution was quenched with dichloromethane, washed 2× with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give a mixture of 6,8-dichloro-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide and 8-bromo-6-chloro-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (202 mg, 0.656 mmol, 60.8% yield). LC/MS, m/z 307.93 (M+1). HPLC Rt, 1.49 min. Waters Sunfire C18 column (4.6×50 mm) 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

1. additionTo a 2 dram vial was added
2. customThe solvent and excess oxalyl chloride were removed in vacuo
3. dissolutionThe residue was dissolved in dichloromethane (2 mL)
4. stirringThe reaction solution was stirred at 25° C. for 6 hours
5. customThe solution was quenched with dichloromethane
6. washwashed 2× with water
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationconcentrated in vacuo
9. customto give

ORD-Eintrag

ord-0515d564b3104f1da39c97d34702118d

Quelldatensatz

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08389527B2