Methanesulfonic Acid → 3-amino-8-bromo-1,5-dimethyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one
Reaction equation
[Br:1][C:2]1[CH:26]=[CH:25][C:5]2[C:6]([CH3:24])=[N:7][CH:8]([NH:13]C(=O)OCC3C=CC=CC=3)[C:9](=[O:12])[N:10]([CH3:11])[C:4]=2[CH:3]=1.CS(O)(=O)=O.[OH-].[NH4+]>C1(OC)C=CC=CC=1>[NH2:13][CH:8]1[N:7]=[C:6]([CH3:24])[C:5]2[CH:25]=[CH:26][C:2]([Br:1])=[CH:3][C:4]=2[N:10]([CH3:11])[C:9]1=[O:12]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 40 °C
Procedure
162c (0.831 g, 2.00 mmol) was dissolved in anhydrous anisole (16 ml) and then methane sulfonic acid (3.84 g, 40 mmol) was added in one portion, and then the reaction was heated to 40° C. for 30 minutes with stirring. The reaction was cooled to 0° C. in an ice bath then basified to pH=10 with concentrated ammonium hydroxide. The aqueous solution was then extracted with chloroform (3×50 ml) and the organic layers combined, dried over magnesium sulfate, filtered and the filtrate concentrated to give a residue. The residue was purified to silica gel column chromatography eluting with 10% methyl alcohol in chloroform to give the title compound 162d (0.463 g, 82%). 1H NMR (CDCl3, 300 MHz): δ 7.32-7.23 (m, 3H), 4.12 (d, 1H, J=1.1 Hz), 3.27 (s, 3H), 2.30 (d, 3H, J=1.5 Hz) ppm.
Workup
- temperatureThe reaction was cooled to 0° C. in an ice bath
- extractionThe aqueous solution was then extracted with chloroform (3×50 ml)
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationthe filtrate concentrated
- customto give a residue
- customThe residue was purified to silica gel column chromatography
- washeluting with 10% methyl alcohol in chloroform
Sources & evidence
- ORD record
- ord-63417533397f45b598c1235c8fe46f69
- Source dataset
- uspto-grants-2003_01
- Patent number
- US06503902B2
Reaction notes
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