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

HRID 1959660Notes

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. Solvents was then removed. The residue was diluted with water and pH was adjusted to 8-10 with 6N NaOH solution. The product was extracted by DCM and the combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (3% to 10% MeOH in DCM) to afford 260 mg (72%) of the title compound. LCMS (method B): [MH]+=327, tR=2.52 min.

Workup

customSolvents was then removed
additionThe residue was diluted with water and pH
extractionThe product was extracted by DCM
washthe combined organic layers were washed with brine
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography (3% to 10% MeOH in DCM)

Sources & evidence

ORD record: ord-372975d5dbcb4fd4a6aa18dcee7ee277
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08410264B2

Reaction notes

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