tert-Butanol → Tert-butyl [6-(3-{[3-(trifluoromethyl)benzoyl]amino}phenoxy)imidazo[1,2-b]pyridazin-2-yl]carbamate

HRID 2391189Notes

Reaction equation

HRID 2391189 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([CH:28]=[CH:29][CH:30]=1)[C:6]([NH:8][C:9]1[CH:10]=[C:11]([CH:25]=[CH:26][CH:27]=1)[O:12][C:13]1[CH:14]=[CH:15][C:16]2[N:17]([CH:19]=[C:20](C(O)=O)[N:21]=2)[N:18]=1)=[O:7].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:40])C=CC=CC=1.C([N:52]([CH2:55]C)CC)C.[C:57]([OH:61])([CH3:60])([CH3:59])[CH3:58]>C(OCC)(=O)C>[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([CH:28]=[CH:29][CH:30]=1)[C:6]([NH:8][C:9]1[CH:10]=[C:11]([CH:25]=[CH:26][CH:27]=1)[O:12][C:13]1[CH:14]=[CH:15][C:16]2[N:17]([CH:19]=[C:20]([NH:52][C:55](=[O:40])[O:61][C:57]([CH3:60])([CH3:59])[CH3:58])[N:21]=2)[N:18]=1)=[O:7]

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 573875936-(3-{[3-(Trifluoromethyl)benzoyl]amino}phenoxy)imidazo[1,2-b]pyridazine-2-carboxylic acid

Product 1

HCID 57387816Tert-butyl [6-(3-{[3-(trifluoromethyl)benzoyl]amino}phenoxy)imidazo[1,2-b]pyridazin-2-yl]carbamateYield 39%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 6-(3-{[3-(trifluoromethyl)benzoyl]amino}phenoxy)imidazo[1,2-b]pyridazine-2-carboxylic acid (111 mg, 0.25 mmol), diphenylphosphoryl azide (103 mg, 0.375 mmol), triethylamine (51 mg, 0.5 mmol) and tert-butanol (5.0 mL) was stirred at room temperature for 5 min, heated to 100° C. and stirred overnight. After allowing the reaction mixture to cool to room temperature, ethyl acetate was added to the mixture, and the mixture was washed with saturated aqueous sodium hydrogencarbonate solution, dried over anhydrous magnesium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/19→ethyl acetate alone) to give the title compound (79 mg, 39%) as a white solid.

Workup

  1. temperatureheated to 100° C.
  2. stirringstirred overnight
  3. temperatureto cool to room temperature
  4. washthe mixture was washed with saturated aqueous sodium hydrogencarbonate solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltrated
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/19→ethyl acetate alone)

Sources & evidence

ORD record
ord-24fb434191e44aa7b02b517b37e6f555
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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