Iodine → 3-((6-Chloro-3-cyanoimidazo[1,2-b]pyridazin-8-yl)(4-methoxybenzyl)amino)benzoic acid

Temperatur

80 °C

A solution of 253B (100 mg, 0.20 mmol) in acetonitrile (5 mL) was treated with iodine (15.54 mg, 0.061 mmol) and water (50 μL, 2.78 mmol). The reaction mixture was stirred at 80° C. for 8 hours. The reaction mixture was diluted with ethyl acetate, and washed with water. The aqueous layer was extracted with ethyl acetate (4×20 mL). The pooled organic phase was dried over Na2SO4 and concentrated. The residue was triturated with DCM and filtered. The filtrate was concentrated, dissolved in DCM, and purified by flash chromatography, silica column (12 g, gradient elution from hexanes-ethyl acetate in 15 min.). The appropriate fraction was concentrated under reduced pressure and dried in vacuo to yield 253C (57.5 mg, 64.9% yield) as a yellow solid. HPLC: Rt=4.23 min. (PHENOMENEX® Luna C18 4.6×30 mm 3 u, A10-90% aqueous methanol containing 0.1% TFA in 2 min; 4 mL/min flow). MS (ES): m/z=434.0 [M+H]+.

1. washwashed with water
2. extractionThe aqueous layer was extracted with ethyl acetate (4×20 mL)
3. dry with materialThe pooled organic phase was dried over Na2SO4
4. concentrationconcentrated
5. customThe residue was triturated with DCM
6. filtrationfiltered
7. concentrationThe filtrate was concentrated
8. dissolutiondissolved in DCM
9. custompurified by flash chromatography, silica column (12 g, gradient elution from hexanes-ethyl acetate in 15 min.)
10. concentrationThe appropriate fraction was concentrated under reduced pressure
11. customdried in vacuo

ORD-Eintrag

ord-18d7c9de9dfb48aeb32f7f665027f1aa

Quelldatensatz

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09371328B2