Hydrochloric Acid → HCID 57752696, compound

HRID 226094Notes

Reaction equation

HRID 226094 reaction equation
[CH3:1][O:2][C:3]1[C:8]2[C:9]([CH3:12])=[CH:10][O:11][C:7]=2[CH:6]=[CH:5][CH:4]=1.C([Li])CCC.[CH2:18]([CH:20]([C:23]1[C:24]2[N:25]([C:30](I)=[C:31]([CH3:33])[N:32]=2)[N:26]=[C:27]([CH3:29])[CH:28]=1)[CH2:21][CH3:22])[CH3:19].Cl>[Cl-].[Zn+2].[Cl-].C1COCC1>[CH3:1][O:2][C:3]1[C:8]2[C:9]([CH3:12])=[C:10]([C:30]3[N:25]4[N:26]=[C:27]([CH3:29])[CH:28]=[C:23]([CH:20]([CH2:18][CH3:19])[CH2:21][CH3:22])[C:24]4=[N:32][C:31]=3[CH3:33])[O:11][C:7]=2[CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 577526818-(1-Ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 66842179HCID 66842179, compoundHCID 178418339Butyllithium

Product 1

HCID 57752696HCID 57752696, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

4-Methoxy-3-methyl-benzofuran (240 mg, 1.50 mmol) added to THF (6 ml) and cooled to −72° C. n-Butyl lithium (1.0 ml, 1.60 mmol) added and stirred for 5 minutes, warmed to ambient temperature for 10 minutes and cooled again to −72° C. Zinc chloride (0.5 N in THF, 3.2 ml, 1.6 mmol) added, stirred for 5 minutes then warmed to ambient temperature and stirred for 10 minutes. 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (240 mg, 0.69 mmol) and PdCl2(dppf)-CH2Cl2 complex (Aldrich, 64 mg, 0.08 mmol) are added. The mixture is heated to 60° C. for 4 hrs, cooled to ambient temperature, added to HCl (1N) and extracted twice with EtOAc. The combined organic extracts are dried over Na2SO4, filtered and concentrated. The crude product is purified by chromatography using a hexane-ethyl acetate gradient (100% hexane to 30% ethyl acetate in hexane) to give the title compound (54 mg, 21% yield). ES-MS (m/z): calc'd for C23H27N3O2: 377.5. found 378.1 (M+H)+1H NMR (400 mHz, CDCl3): δ 7.27 (t, 1H), 7.18 (d, 1H), 6.74 (s, 1H), 6.70 (d, 1H), 3.99 (s, 3H), 3.39 (bs, 1H), 2.55 (s, 3H), 2.54 (s, 3H), 2.41 (s, 3H), 1.87 (m, 4H), 0.91 (t, 6H) ppm.

Workup

  1. additionadded
  2. temperaturecooled again to −72° C
  3. stirringstirred for 5 minutes
  4. temperaturethen warmed to ambient temperature
  5. stirringstirred for 10 minutes
  6. temperatureThe mixture is heated to 60° C. for 4 hrs
  7. temperaturecooled to ambient temperature
  8. extractionextracted twice with EtOAc
  9. dry with materialThe combined organic extracts are dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product is purified by chromatography

Sources & evidence

ORD record
ord-c1180d61fd7c4c0f8bf31cd5dc780ff5
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Reaction notes

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