Aniline → HCID 178511621, compound

In a 2 dram reaction vial containing acetonitrile (1 mL) at ambient temperature was added 6-chloro-8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazine-3-carboxylic acid (0.025 g, 0.06 mmol), aniline (0.008 g, 0.09 mmol), EDCI (0.018 g, 0.09 mmol), HOBt (0.012 g, 0.09 mmol), and triethylamine (0.025 mL, 0.18 mmol). The suspension was stirred overnight at room temperature. The reaction mixture was then concentrated in vacuo and the residue mixed with trans-1,4-diaminocyclohexane (0.5 g, 4.39 mmol) and heated to 160° C. for 5 h. After cooling to room temperature, the reaction mixture was diluted with DCM/water and the layers separated. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in DCM (1 mL) at room temperature and charged with TFA (1 mL). The mixture stirred 3 h, whereupon the volatiles were removed via a stream of nitrogen and the crude mixture was purified via preparative HPLC (Waters Sunfire column 5u, 100 A, 19×100 mm, 20-100% Solvent B, (Solvent A (90% water, 10% methanol, 0.1% TFA), Solvent B (10% water, 90% methanol, 0.1% TFA), 10 min gradient, 10 minute run, 25 mL/min), affording the title compound, 6-((trans)-4-aminocyclohexylamino)-N-phenyl-8-(phenylamino)imidazo[1,2-b]pyridazine-3-carboxamide. HPLC: Rt=3.02 min. (Waters sunfire 4.6×50 mm C18.5 um 4 min/1 min hold time 0-100% (A-B) A=10% MeOH-90% water-0.1% TFA, B=90% MeOH-10% water-0.1% TFA). MS: [M+H]=442.

1. customIn a 2 dram reaction
2. concentrationThe reaction mixture was then concentrated in vacuo
3. temperatureheated to 160° C. for 5 h
4. temperatureAfter cooling to room temperature
5. customthe layers separated
6. dry with materialThe organic phase was dried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. dissolutionThe residue was dissolved in DCM (1 mL) at room temperature
10. additioncharged with TFA (1 mL)
11. stirringThe mixture stirred 3 h, whereupon the volatiles
12. customwere removed via a stream of nitrogen
13. customthe crude mixture was purified via preparative HPLC (Waters Sunfire column 5u, 100 A, 19×100 mm, 20-100% Solvent B, (Solvent A (90% water, 10% methanol, 0.1% TFA), Solvent B (10% water, 90% methanol, 0.1% TFA), 10 min gradient, 10 minute run, 25 mL/min),

ORD record

ord-dee264ff821549aa87bea70cbe8f49f7

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08389527B2