Hydrogen Peroxide → 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene-1-carboxylic acid amide
Reaction equation
[I:1][C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[C:3]=1[C:24]#[N:25].[OH-].[Na+].OO.[O-:30]S([O-])(=S)=O.[Na+].[Na+]>CO>[I:1][C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:14][CH2:15][N:16]([CH3:19])[CH2:17][CH2:18]2)[C:3]=1[C:24]([NH2:25])=[O:30]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene-1-carbonitrile (example 221A) (220 mg, 0.5 mmole) in MeOH (3 mL) cooled at 0° C. is added dropwise a solution of 1N NaOH (1 mL) and 30% H2O2 (0.1 mL). The reaction mixture is stirred at 0° C. for 1 hour, then aqueous 1N Na2S2O3 is added. The aqueous phase is extracted with AcOEt. The organic phase is dried over MgSO4, filtered and the solvent removed under reduced pressure. The residue is purified by silica gel chromatography eluting with (CH2Cl2:MeOH:NH4OH) from (100:0:0) to (90:10:1) to give 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene-1-carboxylic acid amide melting at 85° C.
Workup
- extractionThe aqueous phase is extracted with AcOEt
- dry with materialThe organic phase is dried over MgSO4
- filtrationfiltered
- customthe solvent removed under reduced pressure
- customThe residue is purified by silica gel chromatography
- washeluting with (CH2Cl2:MeOH:NH4OH) from (100:0:0) to (90:10:1)
Sources & evidence
- ORD record
- ord-22a8d85962de4afa9514308c836385c0
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09255101B2
Reaction notes
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