1-Methylpyrrole → HCID 57932973, compound

HRID 1432661Notes

Reaction equation

HRID 1432661 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[CH:3]1.[Li]C(C)(C)C.[CH2:12]([CH:14]([C:17]1[C:18]2[N:19]([C:24](I)=[C:25]([CH3:27])[N:26]=2)[N:20]=[C:21]([CH3:23])[CH:22]=1)[CH2:15][CH3:16])[CH3:13].[NH4+].[Cl-]>[Cl-].[Cl-].[Zn+2].C1COCC1>[CH2:12]([CH:14]([C:17]1[C:18]2[N:19]([C:24]([C:3]3[N:2]([CH3:1])[CH:6]=[CH:5][CH:4]=3)=[C:25]([CH3:27])[N:26]=2)[N:20]=[C:21]([CH3:23])[CH:22]=1)[CH2:15][CH3:16])[CH3:13]

Participants

7

Reactant 4

HCID 73041-MethylpyrroleHCID 25517Ammonium ChlorideHCID 577526818-(1-Ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418306HCID 178418306, compound

Product 1

HCID 57932973HCID 57932973, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A THF solution (10 mL) of N-methylpyrrole (Aldrich, 800 μL, 9.0 mmol) is cooled to −78° C. under N2 then treated with tert-BuLi (1.7 M in pentane, 5.3 mL, 9.0 mmol). The solution is warmed to room temperature for 30 minutes then cooled to −78° C. and treated with ZnCl2 (Aldrich, 0.5 M in THF, 18 mL, 9.0 mmol). The resulting mixture is warmed to room temperature and treated with a THF slurry (5 mL) containing 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (1.02 gm, 3.0 mmol) and PdCl2(dppf)-CH2Cl2 complex (Aldrich, 140 mg, 0.17 mmol). The mixture is heated to 60° C. overnight, then poured into sat'd aq NH4Cl (50 mL) and extracted with diethyl ether (75 mL). The organic extract is ished with aq. brine, dried over Na2SO4, filtered, and concentrated. The crude product is purified by chromatography using hexane-ethyl acetate gradient (100% hexane to 20% ethyl acetate in hexane) to elute the title compound (407.5 mg, 46% yield) as an oil.

Workup

  1. temperaturethen cooled to −78° C.
  2. temperatureThe resulting mixture is warmed to room temperature
  3. temperatureThe mixture is heated to 60° C. overnight
  4. extractionextracted with diethyl ether (75 mL)
  5. extractionThe organic extract
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product is purified by chromatography

Sources & evidence

ORD record
ord-30be00466af742178707e4d0d6e2f675
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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