Hexane → 8-(1-Ethyl-propyl)-2,6-dimethyl-3-(3-methyl-thieno[3,2-b]pyridin-2-yl)-imidazo[1,2-b]pyridazine

HRID 226063Notes

Reaction equation

HRID 226063 reaction equation
[CH3:1][C:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[S:4][CH:3]=1.[Li]CCCC.CCCCCC.[CH2:22]([CH:24]([C:27]1[C:28]2[N:29]([C:34](I)=[C:35]([CH3:37])[N:36]=2)[N:30]=[C:31]([CH3:33])[CH:32]=1)[CH2:25][CH3:26])[CH3:23]>C1COCC1.[Cl-].[Cl-].[Zn+2]>[CH2:22]([CH:24]([C:27]1[C:28]2[N:29]([C:34]([C:3]3[S:4][C:5]4[C:6](=[N:7][CH:8]=[CH:9][CH:10]=4)[C:2]=3[CH3:1])=[C:35]([CH3:37])[N:36]=2)[N:30]=[C:31]([CH3:33])[CH:32]=1)[CH2:25][CH3:26])[CH3:23]

Participants

7

Reactant 4

HCID 8058HexaneHCID 577526103-Methylthieno[3,2-b]pyridineHCID 577526818-(1-Ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418339Butyllithium

Product 1

HCID 577526518-(1-Ethyl-propyl)-2,6-dimethyl-3-(3-methyl-thieno[3,2-b]pyridin-2-yl)-imidazo[1,2-b]pyridazineYield 35%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

190 mg of 3-Methyl-thieno[3,2-b]pyridine (1.28 mmol) is dissolved in 3.0 ml of dry THF and cooled to −78° C. 0.62 ml of n-BuLi 2.5M in hexane (1.54 mmol) is added at −78° C. and stirred at −78° C. for 10 min and room temperature for 10 min. The reaction vessel is cooled to −78° C. again and 3.3 ml of 0.5 M ZnCl2 in THF (1.66 mmol) is added at −78C and stirred at room temperature for 15 min. 343 mg of 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (1.0 mmol) and 41 mg of PdCl2(pddf) (0.05 mmol) are added and the tube is capped. The tube is heated at 80° C. for overnight. The reaction is quenched by NH4Claq. and extracted by CH2Cl2, dried over Na2SO4 and evaporated. The crude product is applied onto a silica-gel chromatography column (Hexane:AcOEt:2 M NH3 in MeOH=10:3:1) to give 127 mg of the title compound. Yield 35%. mass spectrum (m/e): 365 (M+1); 1H-NMR (CDCl3): 8.79 (dd, 1H, J=4.8 Hz, 1.4 Hz), 8.21 (dd, 1H, J=7.9 Hz, 1.4 Hz), 7.33 (dd, 1H, J=7.9 Hz, 4.8 Hz), 6.76 (s, 1H), 3.38 (m, 1H), 2.55 (s, 6H), 2.47 (s, 3H), 1.89 (m, 4H), 0.92 (t, 6H, J=7.5 Hz) ppm.

Workup

  1. temperatureThe reaction vessel is cooled to −78° C. again
  2. stirringstirred at room temperature for 15 min
  3. customthe tube is capped
  4. temperatureThe tube is heated at 80° C. for overnight
  5. customThe reaction is quenched by NH4Claq
  6. extractionand extracted by CH2Cl2
  7. dry with materialdried over Na2SO4
  8. customevaporated

Sources & evidence

ORD record
ord-20e5affdfb3341a7985ff97d5b49fa93
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Reaction notes

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