Dimethylformamide → N-[6-(3-amino-4-fluorophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

HRID 1663767Notes

Reaction equation

I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])[N:10]=2)[N:7]=1.[NH2:17][C:18]1[CH:19]=[C:20]([OH:25])[CH:21]=[CH:22][C:23]=1[F:24].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>[Cl-].[Na+].O.O1CCCC1.C(OCC)(=O)C>[NH2:17][C:18]1[CH:19]=[C:20]([CH:21]=[CH:22][C:23]=1[F:24])[O:25][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11][C:12]([CH:14]3[CH2:16][CH2:15]3)=[O:13])[N:10]=2)[N:7]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of N-(6-iodoimidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide (2.62 g, 8.0 mmol), 3-amino-4-fluorophenol (2.03 g, 16.0 mmol), potassium carbonate (1.66 g, 12.0 mmol) and N,N-dimethylformamide (20 mL) was stirred at 150° C. for 15 hr. Tetrahydrofuran/ethyl acetate and saturated brine were added to the reaction mixture, and insoluble material was filtered off. The filtrate was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=20/80→0/100) and recrystallized from ethyl acetate to give the title compound (1.91 g, 73%) as pale-yellow crystals.

Workup

filtrationwas filtered off
extractionThe filtrate was extracted with ethyl acetate
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltrated
customThe solvent was evaporated under reduced pressure
customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=20/80→0/100)
customrecrystallized from ethyl acetate

Sources & evidence

ORD record: ord-821bbd28d38c491f975b02233e18802e
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08034812B2

Reaction notes

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