1-{3-[8-(1-Ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl]-2-methyl-imidazo[1,2-a]pyridin-8-yl}-ethanone → 2-{3-[8-(1-Ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl]-2-methyl-imidazo[1,2-a]pyridin-8-yl}-propan-2-ol

HRID 226051Notes

Reaction equation

HRID 226051 reaction equation
[CH3:1][Mg+].[Br-].[CH2:4]([CH:6]([C:9]1[C:10]2[N:11]([C:16]([C:20]3[N:24]4[CH:25]=[CH:26][CH:27]=[C:28]([C:29](=[O:31])[CH3:30])[C:23]4=[N:22][C:21]=3[CH3:32])=[C:17]([CH3:19])[N:18]=2)[N:12]=[C:13]([CH3:15])[CH:14]=1)[CH2:7][CH3:8])[CH3:5]>C1COCC1>[CH2:4]([CH:6]([C:9]1[C:10]2[N:11]([C:16]([C:20]3[N:24]4[CH:25]=[CH:26][CH:27]=[C:28]([C:29]([OH:31])([CH3:1])[CH3:30])[C:23]4=[N:22][C:21]=3[CH3:32])=[C:17]([CH3:19])[N:18]=2)[N:12]=[C:13]([CH3:15])[CH:14]=1)[CH2:7][CH3:8])[CH3:5]

Participants

4

Reactant 2

HCID 577526751-{3-[8-(1-Ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl]-2-methyl-imidazo[1,2-a]pyridin-8-yl}-ethanoneHCID 178418689HCID 178418689, compound

Product 1

HCID 577526202-{3-[8-(1-Ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl]-2-methyl-imidazo[1,2-a]pyridin-8-yl}-propan-2-olYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of CeCl3 (0.37 g, 2.22 mmol) in THF (10 mL) is stirred at RT for 2 h. It is then cooled to 0° C., and treated with 3.0 M CH3MgBr (0.74 mL, 2.22 mmol). The mixture is stirred at 0° C. for 2 h. A solution of 1-{3-[8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl]-2-methyl-imidazo[1,2-a]pyridin-8-yl}-ethanone (0.57 g, 1.48 mmol) in THF (5 mL) is added to the mixture at 0° C. The reaction is stirred at 0° C. for 30 min and at RT for 2 h. It is finally quenched with sat. NH4Cl (10 mL), diluted with H2O (50 mL); extracted with EtOAc (3×100 mL). The combined organic layers is dried with Na2SO4, filtered and concentrated. Purification of the crude material by silica gel chromatography gives the title compound (0.36 g, 0.90 mmol, 61%). 1H NMR (CDCl3): δ 0.92 (t, J=7.5 Hz, 3H), 0.93 (t, J=7.5 Hz, 3H), 1.80 (s, 6H), 1.80-1.95 (m, 4H), 2.41 (s, 3H), 2.42 (s, 3H), 2.45 (s, 3H), 3.31-3.41 (m, 1H), 6.67-6.74 (m, 1H), 6.73 (s, 1H), 6.92 (bs, 1H), 7.09 (bs, 1H), 7.41 (d, J=5.6 Hz, 1H) ppm. ES-MS (m/z): calcd for C24H31N5O (M+H)+: 406.6. found: 406.3.

Workup

  1. temperatureIt is then cooled to 0° C.
  2. stirringThe mixture is stirred at 0° C. for 2 h
  3. stirringThe reaction is stirred at 0° C. for 30 min and at RT for 2 h
  4. customIt is finally quenched with sat. NH4Cl (10 mL)
  5. additiondiluted with H2O (50 mL)
  6. extractionextracted with EtOAc (3×100 mL)
  7. dry with materialThe combined organic layers is dried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification of the crude material by silica gel chromatography

Sources & evidence

ORD record
ord-f9f09b57bf304cc4be560fa77b291d8e
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Reaction notes

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