Iodine → 2-[4-(2-Methoxyethoxy)phenyl]-6-butylimidazo[1,2-b]pyridazine

HRID 2356251Notes

Reaction equation

HRID 2356251 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]3[CH:19]=[CH:18][C:17](Cl)=[N:16][N:15]3[CH:21]=2)=[CH:8][CH:7]=1.[CH2:22]([Mg]Br)[CH2:23][CH2:24][CH3:25].BrCCCC.[Mg].II.[Cl-].[NH4+]>O1CCCC1.Cl[Ni]Cl>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]3[CH:19]=[CH:18][C:17]([CH2:22][CH2:23][CH2:24][CH3:25])=[N:16][N:15]3[CH:21]=2)=[CH:8][CH:7]=1

Participants

9

Reactant 6

HCID 807IodineHCID 8002Butyl bromideHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 866002492-[4-(2-Methoxyethoxy)phenyl]-6-chloroimidazo[1,2-b]pyridazineHCID 178418682HCID 178418682, compound

Product 1

HCID 114046012-[4-(2-Methoxyethoxy)phenyl]-6-butylimidazo[1,2-b]pyridazine

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-[4-(2-methoxyethoxy)phenyl]-6-chloroimidazo[1,2-b]pyridazine (304 mg, 1 mmol) in tetrahydrofuran (7 mL) was added with stirring to a solution of butylmagnesium bromide (10 mmol) (prepared from 1-bromobutane (1.37 g, 10 mmol) and magnesium turnings (0.27 g, 11 mmol) and a crystal of iodine in tetrahydrofuran (8 mL)) under an atmosphere of nitrogen. [1,3-Bis(diphenyl-phosphino)propane] dichloronickel(II) (81 mg, 0.15 mmol) was added and the resulting mixture was stirred at room temperature overnight. Saturated, aqueous ammonium chloride solution was added and the resulting mixture extracted with ether (100 mL). The organic layer was washed with brine (80 mL), dried and evaporated. The residue was radially chromatographed on silica gel. Elution with 1-3% methanol in dichloromethane provided Compound 82 (8 mg) as a brown solid. 1H n.m.r. (CDCl3) δ 0.97, t, J=7.3 Hz, 3H; 1.32-1.52, m, 2H; 1.64-1.84, m, 2H; 2.83, t, J=7.5 Hz, 2H; 3.47, s, 3H; 3.72-3.82, m, 2H; 4.12-4.22, m, 2H; 6.92-7.06, m, 3H; 7.86-7.94, m, 3H; 8.10, s, 1H. Mass spectrum (APCI+) m/z 326 (M+H, 100%).

Workup

  1. extractionthe resulting mixture extracted with ether (100 mL)
  2. washThe organic layer was washed with brine (80 mL)
  3. customdried
  4. customevaporated
  5. customThe residue was radially chromatographed on silica gel
  6. washElution with 1-3% methanol in dichloromethane provided Compound 82 (8 mg) as a brown solid

Sources & evidence

ORD record
ord-ff252ea0e9e74398b49a2c9b3f005d36
Source dataset
uspto-grants-2010_07
Patent number
US07759349B2

Reaction notes

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