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
The product of Step 3 (0.831 g, 2.00 mmol) was dissolved in anhydrous anisole (16 ml) and then methanesulfonic acid (3.84 g, 40 mmol) was added in one portion. The reaction mixture was heated to 40° C. for 30 minutes with stirring, then cooled to 0° C. in an ice bath and made basic (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 concentrated to give the crude product. Purification on silica gel, eluting with 10% methyl alcohol in chloroform, providing the title compound as an XXXX (0.463 g, 82%). 1H NMR (CDCl3, 300 MHz): δ 7.32-7.23 (m, 3 H), 4.12 (d, 1 H, J=1.1 Hz), 3.27 (s, 3 H), 2.30 (d, 3 H, J=1.5 Hz) ppm.
Workup
- temperaturecooled 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
- concentrationconcentrated
- customto give the crude product
- customPurification on silica gel
- washeluting with 10% methyl alcohol in chloroform
Sources & evidence
- ORD record
- ord-1b16da4397874987840b76606626bd9b
- Source dataset
- uspto-grants-2008_04
- Patent number
- US07354914B2
Reaction notes
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