Sodium Hydroxide → (6-(5-Cyclopropylisoxazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methanamine

HRID 1513833Notes

Reaction equation

HRID 1513833 reaction equation
[OH:1]/[N:2]=[CH:3]/[C:4]1[CH:5]=[CH:6][C:7]2[N:8]([C:10]([CH2:13][NH:14]C(=O)OC(C)(C)C)=[N:11][N:12]=2)[N:9]=1.[CH:22]([C:24]1[CH:25]=[CH:26][C:27]2N(C(CNC(=O)OC(C)(C)C)=NN=2)N=1)=O.Cl.NO.[OH-].[Na+]>C1COCC1>[CH:25]1([C:24]2[O:1][N:2]=[C:3]([C:4]3[CH:5]=[CH:6][C:7]4[N:8]([C:10]([CH2:13][NH2:14])=[N:11][N:12]=4)[N:9]=3)[CH:22]=2)[CH2:26][CH2:27]1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 57691111Tert-butyl (6-formyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamateHCID 135987477tert-butyl N-[[6-[(E)-hydroxyiminomethyl]-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl]carbamate

Product 1

HCID 57691172(6-(5-Cyclopropylisoxazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methanamineYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(E)-tert-butyl (6-((hydroxyimino)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate. Tert-butyl (6-formyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (400 mg, 1.44 mmol) and hydroxylamine hydrochloride (200 mg, 2.86 mmol) were combined in a flask with 25 mL of THF and 25 mL of 1 N NaOH solution. Stirred at rt for 1 h. Then added dichloromethane (50 mL) and extracted the aqueous layer 3 times with DCM (50 mL), dried over Na2SO4 and concentrated. Purified the oxime via MPLC (DCM/MeOH+1% NH4OH) to give title compound (200 mg, 47% yield) as a tan solid.

Workup

  1. extractionThen added dichloromethane (50 mL) and extracted the aqueous layer 3 times with DCM (50 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customPurified the oxime via MPLC (DCM/MeOH+1% NH4OH)

Sources & evidence

ORD record
ord-63b25f0ce20542938d194afb0cc7d474
Source dataset
uspto-grants-2012_07
Patent number
US08217177B2

Reaction notes

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