Sodium hydride → 6-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylic acid ethyl ester

HRID 548890Notes

Reaction equation

HRID 548890 reaction equation
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][OH:14].[H-].[Na+].[CH2:17]([O:19][C:20]([C:22]1[N:26]2[N:27]=[C:28](Cl)[CH:29]=[CH:30][C:25]2=[N:24][N:23]=1)=[O:21])[CH3:18]>CN(C=O)C>[CH2:17]([O:19][C:20]([C:22]1[N:26]2[N:27]=[C:28]([O:14][CH2:13][C:3]3[C:4]([C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)=[N:5][O:6][C:2]=3[CH3:1])[CH:29]=[CH:30][C:25]2=[N:24][N:23]=1)=[O:21])[CH3:18]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2776149(5-Methyl-3-phenyl-1,2-oxazol-4-yl)methanolHCID 11287584Ethyl 6-chloro-(1,2,4)triazolo(4,3-b)pyridazine-3-carboxylate

Product 1

HCID 426303736-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylic acid ethyl esterYield 16.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (5-methyl-3-phenyl-isoxazol-4-yl)-methanol (60 mg, 0.32 mmol) in DMF (2 mL) was added sodium hydride (55% dispersion in mineral oil, 15 mg, 0.35 mmol). The mixture was stirred at room temperature overnight. After addition of a solution of 6-chloro-1,2,4-triazolo[4,3-b]pyridazine-3-carboxylic acid ethyl ester (79 mg, 0.35 mmol) in DMF (2 mL) the mixture was stirred at room temperature overnight. Then the mixture was evaporated, extracted (ethyl acetate/water) and the organic phase was dried with sodium sulfate and concentrated. Purification by preparative HPLC on reversed phase eluting with acetonitrile/water [0.1% aq NH3 (25%)] afforded the title compound (20 mg, 14%) as a white solid. MS: m/e=380.0 [M+H]+.

Workup

  1. stirringwas stirred at room temperature overnight
  2. customThen the mixture was evaporated
  3. extractionextracted (ethyl acetate/water)
  4. dry with materialthe organic phase was dried with sodium sulfate
  5. concentrationconcentrated
  6. customPurification by preparative HPLC on reversed phase
  7. washeluting with acetonitrile/water [0.1% aq NH3 (25%)]

Sources & evidence

ORD record
ord-fc1729bf87524ff4ace16bb100a9084e
Source dataset
uspto-grants-2011_05
Patent number
US07943619B2

Reaction notes

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