tert-Butanol → HCID 22024608, compound

HRID 501036Notes

Reaction equation

HRID 501036 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]3[N:11]([C:15](C(O)=O)=[C:16]([S:18][CH3:19])[N:17]=3)[N:12]=[CH:13][CH:14]=2)=[C:5]([CH3:23])[CH:4]=1.C(O)(C)(C)C.C([N:31](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>C1(C)C=CC=CC=1.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]3[N:11]([C:15]([NH2:31])=[C:16]([S:18][CH3:19])[N:17]=3)[N:12]=[CH:13][CH:14]=2)=[C:5]([CH3:23])[CH:4]=1

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 22024340HCID 22024340, compound

Product 1

HCID 22024608HCID 22024608, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

The resulting 8-(4-methoxy-2-methylphenyl)-2-(methylsulfanyl)imidazo[1,2-b]pyridazine-3-carboxylic acid was dissolved in toluene (10 mL), then tert-butyl alcohol (10 mL), triethylamine (0.49 mL) and diphenylphosphorylazide (0.38 mL) were added thereto, and the mixture was heated at 100° C. for 4 hours. After completion of the reaction, water was added thereto, which was extracted with ethyl acetate, washed with water, dried over anhydrous magnesium sulfate, and evaporated. The resulting Boc compound was dissolved in ethyl acetate (10 mL) without purification, then a 4N hydrochloric acid-ethyl acetate solution (15 mL) was added thereto, and the mixture was stirred at room temperature for 3 hours. Under ice-cooling, a 5N aqueous sodium hydroxide solution was added thereto, which was neutralized and extracted with ethyl acetate. The material was washed with water, dried over anhydrous magnesium sulfate, and evaporated. The resulting residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:2) to give the title compound (73 mg) as a brown oil.

Workup

  1. additionwas added
  2. extractionwhich was extracted with ethyl acetate
  3. washwashed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customevaporated
  6. dissolutionThe resulting Boc compound was dissolved in ethyl acetate (10 mL) without purification
  7. additiona 4N hydrochloric acid-ethyl acetate solution (15 mL) was added
  8. temperatureUnder ice-cooling
  9. additiona 5N aqueous sodium hydroxide solution was added
  10. extractionextracted with ethyl acetate
  11. washThe material was washed with water
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customevaporated
  14. customThe resulting residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:2)

Sources & evidence

ORD record
ord-95931c8f4c73419d933820fce5c6caa0
Source dataset
uspto-grants-2010_08
Patent number
US07772249B2

Reaction notes

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