Potassium Fluoride → (rac)-4-{3-[1-(5,7-Difluoro-quinolin-6-yl)-ethyl]-imidazo[1,2-b]pyridazin-6-yl}-1-methyl-piperazin-2-one

HRID 1942064Notes

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH: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)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.[F-].[K+].Cl.[CH3:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][C:30]1=[O:35]>CN1C(=O)CCC1>[F:24][C:14]1[C:13]([CH:11]([C:8]2[N:6]3[N:7]=[C:2]([N:32]4[CH2:33][CH2:34][N:29]([CH3:28])[C:30](=[O:35])[CH2:31]4)[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)[CH3:12])=[C:22]([F:23])[CH:21]=[C:20]2[C:15]=1[CH:16]=[CH:17][CH:18]=[N:19]2

Participants

Conditions

Temperature: 180 °C

Procedure

(rac)-6-[1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-5,7-difluoro-quinoline (Intermediate C, 50 mg, 0.145 mmol), KF (84 mg, 1.45 mmol) and 1-methylpiperazine-2-one hydrochloride (65 mg, 0.435 mmol) were suspended in NMP (0.483 mL). The RM was stirred at 180° C. for 5 h. The mixture was filtered and the obtained filtrate was purified by reverse phase chromatography (water+0.1% TFA/acetonitrile+0.1% TFA). The collected fractions were concentrated and the residue was dissolved in MeOH, passed through an SPE cartridge of PL-HCO3 MP. The filtrate was concentrated to afford the title compound as a brownish oil (tR 3.19 min (conditions 1), MH+=423).

Workup

filtrationThe mixture was filtered
customthe obtained filtrate was purified by reverse phase chromatography (water+0.1% TFA/acetonitrile+0.1% TFA)
concentrationThe collected fractions were concentrated
dissolutionthe residue was dissolved in MeOH
concentrationwas concentrated

Sources & evidence

ORD record: ord-d70891a8dee34bf49b96d15312ef8b9d
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08389526B2

Reaction notes

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