(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-(5,7-difluoro-quinolin-6-yl)-methanone → (Rac)-1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-1-(5,7-difluoro-quinolin-6-yl)-ethanol

HRID 69225Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:13]3[C:14]([F:24])=[C:15]4[C:20](=[CH:21][C:22]=3[F:23])[N:19]=[CH:18][CH:17]=[CH:16]4)=[O:12])=[CH:9][N:10]=2)[N:7]=1.[CH3:25][Mg]Br>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:13]3[C:14]([F:24])=[C:15]4[C:20](=[CH:21][C:22]=3[F:23])[N:19]=[CH:18][CH:17]=[CH:16]4)([OH:12])[CH3:25])=[CH:9][N:10]=2)[N:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-(5,7-difluoro-quinolin-6-yl)-methanone (Stage 182.3, 3.05 g, 8.41 mmol) was suspended in THF (65 mL) and the mixture was cooled down to 0° C. with an ice bath. Then the methylmagnesium bromide (1.4 M, 15.01 mL) was added slowly. The RM was stirred for 30 min and was then allowed to warm up to rt. After 2 h, it was quenched with a few mL of water. The solution was filtered. The solid residue was washed with water and the filtrate extracted with EtOAc twice. Then the organics were joined and washed with brine, dried over Na2SO4 and the solvent was removed. The crude was purified with DCM and MeOH by MPLC to give the title compound as a yellow solid (tR 0.9 min (conditions 2), MH+=361).

Workup

temperatureto warm up to rt
waitAfter 2 h
customit was quenched with a few mL of water
filtrationThe solution was filtered
washThe solid residue was washed with water
extractionthe filtrate extracted with EtOAc twice
washwashed with brine
dry with materialdried over Na2SO4
customthe solvent was removed
customThe crude was purified with DCM and MeOH by MPLC

Sources & evidence

ORD record: ord-50fbc176012a4eef83f3a892176524b5
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822468B2

Reaction notes

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