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

Temperature

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 record

ord-15d262f1fcc740d2aba008a3f14d52fc

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08252795B2