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

HRID 588539Notes

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-6b468a095f8246e5954feb2ecb2ecc04
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227975B2

Reaction notes

Loading…