1-Butanol → 6-(2-(3-Fluorophenyl)piperidin-1-yl)-3-nitroimidazo[1,2-b]pyridazine

HRID 2096306Notes

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([N+:11]([O-:13])=[O:12])=[CH:9][N:10]=2)[N:7]=1.[F:14][C:15]1[CH:16]=[C:17]([CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][NH:22]2)[CH:18]=[CH:19][CH:20]=1.C(N(C(C)C)C(C)C)C.C(O)CCC>O.CCOC(C)=O>[F:14][C:15]1[CH:16]=[C:17]([CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][N:22]2[C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([N+:11]([O-:13])=[O:12])=[CH:9][N:10]=3)[N:7]=2)[CH:18]=[CH:19][CH:20]=1

Participants

Conditions

Temperature: 180 °C

Procedure

To a pressure reaction tube were charged 6-chloro-3-nitroimidazo[1,2-b]pyridazine (450 mg, 2.27 mmol), 2-(3-fluorophenyl)piperidine (609 mg, 3.40 mmol, purchased from ChemBridge), and N-ethyl-N-isopropylpropan-2-amine (0.51 mL, 2.95 mmol), followed by addition of 1.0 mL n-butanol. The reaction mixture was then sealed and stirred at 180° C. for 24 hours. After completion, the reaction was cooled to ambient temperature, and diluted with water and EtOAc. The organic layer was separated, and the aqueous layer was extracted with EtOAc twice. The combined organic layers was dried over Na2SO4 and concentrated. The crude product was purified by silica column chromatography, eluting with 20 to 50% EtOAc in hexanes to yield the desired product for the next step.

Workup

customTo a pressure reaction tube
customThe reaction mixture was then sealed
temperatureAfter completion, the reaction was cooled to ambient temperature
customThe organic layer was separated
extractionthe aqueous layer was extracted with EtOAc twice
dry with materialThe combined organic layers was dried over Na2SO4
concentrationconcentrated
customThe crude product was purified by silica column chromatography
washeluting with 20 to 50% EtOAc in hexanes

Sources & evidence

ORD record: ord-2e1a11a8ad66481ebea9cc12a070e497
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08450322B2

Reaction notes

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