Cyclopropylacetylene → (6-(5-Cyclopropylisoxazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methanamine
Reaction equation
Cl/[C:2](=[N:21]\[OH:22])/[C:3]1[CH:4]=[CH:5][C:6]2[N:7]([C:9]([CH2:12][NH:13]C(=O)OC(C)(C)C)=[N:10][N:11]=2)[N:8]=1.[C:23]([CH:25]1[CH2:27][CH2:26]1)#[CH:24].C(=O)([O-])O.[K+]>CCOC(C)=O>[CH:25]1([C:23]2[O:22][N:21]=[C:2]([C:3]3[CH:4]=[CH:5][C:6]4[N:7]([C:9]([CH2:12][NH2:13])=[N:10][N:11]=4)[N:8]=3)[CH:24]=2)[CH2:27][CH2:26]1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 60 °C
Procedure
Dissolved (Z)-tert-butyl (6-(chloro(hydroxyimino)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (110 mg, 337 μmol), ethynylcyclopropane (28 μl, 337 μmol), and potassium hydrogencarbonate (67.4 mg, 673 μmol) in 0.3 mL of EtOAc and heated to 60° C. for 12 h to afford the protected intermediate. The solvent was removed by rotary evaporation and the residue was redissolved in dicholoromethane (5 mL) and TFA (2 mL) and stirred for 30 min at room temperature. The solvent was then removed and the residue was redissolved in MeOH. Solid K2CO3 was added and the mixture was stirred for 1 h to free base the title compound. Purified the amine via MPLC (DCM/MeOH+1% NH4OH) to afford the title compound (20 mg, 23% yield).
Workup
- customto afford the protected intermediate
- customThe solvent was removed by rotary evaporation
- dissolutionthe residue was redissolved in dicholoromethane (5 mL) and TFA (2 mL)
- customThe solvent was then removed
- dissolutionthe residue was redissolved in MeOH
- additionSolid K2CO3 was added
- stirringthe mixture was stirred for 1 h to free base the title compound
- customPurified the amine via MPLC (DCM/MeOH+1% NH4OH)
Sources & evidence
- ORD record
- ord-5d8719afbeec4ea88326ddbc578e4955
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09066954B2
Reaction notes
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