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

HRID 1942081Notes

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.Cl.[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[N:35]1[CH2:40][CH2:39][NH:38][CH2:37][C:36]1=[O:41]>CN1C(=O)CCC1>[F:24][C:14]1[C:13]([CH:11]([C:8]2[N:6]3[N:7]=[C:2]([N:38]4[CH2:39][CH2:40][N:35]([C:30]5[CH:31]=[CH:32][CH:33]=[CH:34][N:29]=5)[C:36](=[O:41])[CH2:37]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, 1.450 mmol), 1-(pyridin-2-yl)piperazin-2-one dihydrochloride salt (109 mg, 0.435 mmol) were suspended in NMP (483 μL). The RM was stirred at 180° C. for 16 h. The mixture was purified by preparative UPLC with acetonitrile and water (+0.1% TFA) The fractions were collected and acetonitrile was removed. It was taken up with MeOH and passed through an SPE cartridge of PL-HCO3 MP from polymer lab. The solvent was removed and a brown solid was obtained (tR 1.0 min (conditions 4), MH+=486).

Workup

customThe mixture was purified by preparative UPLC with acetonitrile and water (+0.1% TFA) The fractions
customwere collected
customacetonitrile was removed
customThe solvent was removed
customa brown solid was obtained (tR 1.0 min (conditions 4), MH+=486)

Sources & evidence

ORD record: ord-64b0bf7dba6d4985ade70a966b2ea49a
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08389526B2

Reaction notes

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