Ammonium Chloride → Tert-butyl (6-(1-hydroxyethyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate
Reaction equation
[CH:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:7]([C:9]([CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[N:10][N:11]=2)[N:8]=1)=[O:2].[CH3:21][Mg]Br.[NH4+].[Cl-]>C1COCC1>[OH:2][CH:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:7]([C:9]([CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[N:10][N:11]=2)[N:8]=1)[CH3:21]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
In a 10 mL round bottom flask under N2 was dissolved tert-butyl (6-formyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (200 mg, 721 μmol) in 3 mL of THF then cooled at −78° C. and treated with methylmagnesium bromide (721 μl, 2164 μmol). After 30 minutes, the reaction mixture was warmed to 0° C. over 1 h. After 1 h the reaction mixture based on LC-MS was neutralized with NH4Cl (sat.). The aqueous phase was extracted 3× with DCM then the organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude tert-butyl (6-(1-hydroxyethyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (202 mg, 95.5% yield) was used without further purification in the next step. MS m/z=294.4 [M+1]+. Calc'd for C13H19N5O3: 293.3.
Workup
- temperaturethe reaction mixture was warmed to 0° C. over 1 h
- waitAfter 1 h the reaction mixture based on LC-MS
- extractionThe aqueous phase was extracted 3× with DCM
- dry with materialthe organic layer was dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-2f2218fcf6084a0b8841b28c596236e4
- Source dataset
- uspto-grants-2013_09
- Patent number
- US08524900B2
Reaction notes
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