Iodine → 6-Chloro-3-(1-(6-fluoro-1-methyl-1H-indazol-5-yl)ethyl)imidazo[1,2-b]pyridazine

HRID 456146Notes

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:20](=[CH:21][C:22]=3[F:23])[N:19]([CH3:24])[N:18]=[CH:17]4)(O)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.II.[PH2](=O)O>CC(O)=O>[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:20](=[CH:21][C:22]=3[F:23])[N:19]([CH3:24])[N:18]=[CH:17]4)[CH3:12])=[CH:9][N:10]=2)[N:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 1-(6-chloroimidazo[1,2-b]pyridazin-3-yl)-1-(6-fluoro-1-methyl-1H-indazol-5-yl)ethanol (1.1 g, 3.18 mmol), diiodine (2.019 g, 7.95 mmol), and phosphinic acid (0.840 g, 12.73 mmol) in HOAc (10 ml) was heated to 120° C. for 5 h. After cooling to rt, the reaction mixture was concentrated in vacuo. The residue was taken with water and adjusted its pH tp 8 with aqueous NaOH. The mixture was extracted with DCM, dried over Na2SO4 and concentrated to give a residue, which was purified with silica gel column chromatography (MeOH:EA) to give 6-chloro-3-(1-(6-fluoro-1-methyl-1H-indazol-5-yl)ethyl)imidazo[1,2-b]pyridazine (900 mg 60%). LCMS (method B): [MH]+=330, tR=2.59 min.

Workup

temperatureAfter cooling to rt
concentrationthe reaction mixture was concentrated in vacuo
extractionThe mixture was extracted with DCM
dry with materialdried over Na2SO4
concentrationconcentrated
customto give a residue, which
customwas purified with silica gel column chromatography (MeOH:EA)

Sources & evidence

ORD record: ord-cdfbbd7a232d4c05bdd33cd90e3c3575
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497368B2

Reaction notes

Loading…