1-(6-Chloroimidazo(1,2-b)pyridazin-3-yl)ethan-1-one → 1-(6-Chloroimidazo[1,2-b]pyridazin-3-yl)-1-(6-fluoro-1-methyl-1H-indazol-5-yl)ethanol

HRID 1959707Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[N:7]([CH3:12])[N:6]=[CH:5]2.[Li]CCCC.[Cl:18][C:19]1[CH:20]=[CH:21][C:22]2[N:23]([C:25]([C:28](=[O:30])[CH3:29])=[CH:26][N:27]=2)[N:24]=1>C1COCC1>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]2[N:23]([C:25]([C:28]([C:2]3[CH:3]=[C:4]4[C:8](=[CH:9][C:10]=3[F:11])[N:7]([CH3:12])[N:6]=[CH:5]4)([OH:30])[CH3:29])=[CH:26][N:27]=2)[N:24]=1

Participants

Conditions

Temperature: -100 °C

Procedure

To a solution of 5-bromo-6-fluoro-1-methyl-1H-indazole (intermediate L) (1.800 g, 7.86 mmol) in THF (79 mL) at −100° C. was added n-BuLi (5.40 mL, 8.64 mmol) dropwise. After stirring for 1 h at −100° C., a solution of 1-(6-chloroimidazo[1,2-b]pyridazin-3-yl)ethanone (intermediate M) (1.691 g, 8.64 mmol) in THF (20 mL) was added dropwise. The reaction solution was stirred for additional 2 h and quenched with NH4Cl (aq). The resulting mixture was extracted with EtOAc. The combined organic layers were washed with NH4Cl (aq), dried over Na2SO4 and concentrated in vacuo to afford the crude product which was purified by column chromatography (hexanes:EtOAc) to give the title compound in 34% yield. LCMS (method B): [MH]+=346, tR=2.14 min.

Workup

stirringThe reaction solution was stirred for additional 2 h
customquenched with NH4Cl (aq)
extractionThe resulting mixture was extracted with EtOAc
washThe combined organic layers were washed with NH4Cl (aq)
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customto afford the crude product which
customwas purified by column chromatography (hexanes:EtOAc)

Sources & evidence

ORD record: ord-864eb9c822f14f83bec195ea41e79d7e
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08410264B2

Reaction notes

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