Water → 3-(2,4-dimethyl-2H-pyrazol-3-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 1432695Notes

Reaction equation

HRID 1432695 reaction equation
[Li]CCCC.[CH3:6][N:7]1[CH:11]=[C:10]([CH3:12])[CH:9]=[N:8]1.[CH2:13]([CH:15]([C:18]1[C:19]2[N:20]([C:25](I)=[C:26]([CH3:28])[N:27]=2)[N:21]=[C:22]([CH3:24])[CH:23]=1)[CH2:16][CH3:17])[CH3:14].O>C1COCC1.[Cl-].[Zn+2].[Cl-]>[CH3:6][N:7]1[C:11]([C:25]2[N:20]3[N:21]=[C:22]([CH3:24])[CH:23]=[C:18]([CH:15]([CH2:13][CH3:14])[CH2:16][CH3:17])[C:19]3=[N:27][C:26]=2[CH3:28])=[C:10]([CH3:12])[CH:9]=[N:8]1

Participants

7

Reactant 4

HCID 962WaterHCID 1368361,4-DimethylpyrazoleHCID 577526818-(1-Ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418339Butyllithium

Product 1

HCID 579330113-(2,4-dimethyl-2H-pyrazol-3-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineYield 0.7%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-72 °C

Procedure

n-BuLi (1.3 ml, 2.09 mmol) is stirred in THF (4 ml), under N2, and cooled to −72° C. 1,4-dimethyl-1H-pyrazole (170 mg, 2.04 mmol, in THF, 1 ml) is added slowly, stirred for 5 min. then allowed to warm to ambient temp. and stirred for 45 min. The mixture is cooled to −72° C. and a zinc chloride solution (4.3 ml, 2.14 mmol, 0.5 M in toluene) added, warmed to ambient temp. and treated with 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine and PdCl2(dppf)-CH2Cl2 complex (Aldrich, 40 mg, 0.05 mmol). The mixture is heated to 65° C. overnight, cooled to ambient temp., added to water and extracted twice with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product is purified by chromatography using a hexane-ethyl acetate gradient (100% hexane to 50% ethyl acetate in hexane) to elute the product. The title compound is obtained (0.7% yield). ES-MS (m/z): calc'd for C18H25N5: 311.4; found 312.2 (M+H)+. 1H NMR (400 mHz, CDCl3): δ 7.51 (s, 1H), 6.75 (s, 1H), 3.72 (s, 3H), 3.33 (m, 1H), 2.53 (s, 3H), 2.43 (s, 3H), 2.00 (s, 3H), 1.87 (m, 4H), 0.92 (m, 6H).

Workup

  1. temperatureto warm to ambient temp.
  2. stirringstirred for 45 min
  3. temperatureThe mixture is cooled to −72° C.
  4. temperaturewarmed to ambient temp.
  5. temperatureThe mixture is heated to 65° C. overnight
  6. temperaturecooled to ambient temp.
  7. extractionextracted twice with EtOAc
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product is purified by chromatography
  13. washto elute the product

Sources & evidence

ORD record
ord-0e6b7cabb1a546be85892bbb481723d0
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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