Iodine → 6-(1-(6-Chloroimidazo[1,2-b]pyridazin-3-yl)ethyl)-7-fluoroquinoline

HRID 456086Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][C:23]=3[F:24])[N:20]=[CH:19][CH:18]=[CH:17]4)(O)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.[PH2](=O)O.II>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][C:23]=3[F:24])[N:20]=[CH:19][CH:18]=[CH:17]4)[CH3:12])=[CH:9][N:10]=2)[N:7]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 1-(6-chloroimidazo[1,2-b]pyridazin-3-yl)-1-(7-fluoroquinolin-6-yl)ethanol (420 mg, 1.10 mmol) in acetic acid (20 mL) was added phosphinic acid (50% aqueous solution, 0.60 ml, 5.51 mmol) and iodine (700 mg, 2.76 mmol). The resulting solution was heated at 110° C. overnight and the solvent was removed. The residue was diluted with water and pH was adjusted to 8-10 with 6N NaOH solution. The mixture was then extracted by CH2Cl2, washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (3% to 10% MeOH in CH2Cl2) to afford 260 mg (yield: 72%) title compound. LCMS (method B): [MH]+=327, tR=2.52 min.

Workup

customthe solvent was removed
additionThe residue was diluted with water and pH
extractionThe mixture was then extracted by CH2Cl2
washwashed with brine
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography (3% to 10% MeOH in CH2Cl2)

Sources & evidence

ORD record: ord-7f12d6e30079487394d41ebfdbb889a9
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497368B2

Reaction notes

Loading…