Ethanolamine → 6-{[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-pyridazine-3-carboxylic acid (2-hydroxy-ethyl)-amide

HRID 548882Notes

Reaction equation

HRID 548882 reaction equation
C[Al](C)C.[CH2:5]([CH2:7][NH2:8])[OH:6].C([O:11][C:12]([C:14]1[N:15]=[N:16][C:17]([NH:20][CH2:21][C:22]2[C:23]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)=[N:24][O:25][C:26]=2[CH3:27])=[CH:18][CH:19]=1)=O)C.C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>O1CCOCC1>[OH:6][CH2:5][CH2:7][NH:8][C:12]([C:14]1[N:15]=[N:16][C:17]([NH:20][CH2:21][C:22]2[C:23]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)=[N:24][O:25][C:26]=2[CH3:27])=[CH:18][CH:19]=1)=[O:11]

Participants

6

Reactant 4

HCID 700EthanolamineHCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 671578636-{[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-pyridazine-3-carboxylic acid ethyl ester

Product 1

HCID 671583436-{[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-pyridazine-3-carboxylic acid (2-hydroxy-ethyl)-amideYield 20.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of trimethylaluminium (2 M in toluene, 500 μL, 1.0 mmol) was added dropwise (exothermic) to a solution of ethanolamine (61 mg, 60 μL, 1.0 mmol) in dioxane (6 mL) and the resulting mixture was stirred at room temperature for 1 h. Then a solution of 6-{[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethyl]-amino}-pyridazine-3-carboxylic acid ethyl ester (89 mg, 0.25 mmol) in dioxane (3 mL) was added. The resulting mixture was then heated at 85-95° C. for 4 h and then cooled to room temperature and then poured into a sodium potassium tartrate solution and extracted with ethyl acetate which was then washed with brine, dried over sodium sulfate and evaporated. Purification by chromatography (SiO2, dichloromethane:methanol=100:0 to 9:1) afforded the title compound (19 mg, 20%) which was obtained as a light yellow foam. MS: m/e=372.3 [M+H]+.

Workup

  1. temperatureThe resulting mixture was then heated at 85-95° C. for 4 h
  2. temperaturecooled to room temperature
  3. extractionextracted with ethyl acetate which
  4. washwas then washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customPurification by chromatography (SiO2, dichloromethane:methanol=100:0 to 9:1)

Sources & evidence

ORD record
ord-2f614d7166ad4b509745a8967427953b
Source dataset
uspto-grants-2011_05
Patent number
US07943619B2

Reaction notes

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