Methanol → 4-(5-Bromopyrrolo[1,2-b]pyridazin-4-yloxy)-3-fluoroaniline

HRID 1851087Notes

Reaction equation

HRID 1851087 reaction equation
CO.[Cl-].[NH4+].[Br:5][C:6]1[CH:7]=[CH:8][N:9]2[C:14]=1[C:13]([O:15][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][C:17]=1[F:25])=[CH:12][CH:11]=[N:10]2>O1CCCC1.[Zn]>[Br:5][C:6]1[CH:7]=[CH:8][N:9]2[C:14]=1[C:13]([O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][C:17]=1[F:25])=[CH:12][CH:11]=[N:10]2

Participants

6

Reactant 3

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 58368367HCID 58368367, compound

Product 1

HCID 583683624-(5-Bromopyrrolo[1,2-b]pyridazin-4-yloxy)-3-fluoroanilineYield 93.7%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Methanol (1.2 mL), zinc powder (300 mg, 4.57=1) and ammonium chloride (130 mg, 2.47 mmol) were sequentially added to a solution of 5-bromo-4-(2-fluoro-4-nitrophenoxy)pyrrolo[1,2-b]pyridazine (67 mg, 0.19 mmol) in tetrahydrofuran (4.7 mL) and heated at 70° C. for 1.5 hours. Upon completion of the reaction, the resulting reaction mixture was cooled to room temperature and filtered by passing through a celite pad. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (1-6% ethyl acetate in dichloromethane) to give the target compound (57 mg, 0.178 mmol, 93% yield).

Workup

  1. customUpon completion of the reaction
  2. customthe resulting reaction mixture
  3. temperaturewas cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel chromatography (1-6% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-523771a08dd9416c9a9d409d3a8c2809
Source dataset
uspto-grants-2015_02
Patent number
US08957102B2

Reaction notes

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