Methanesulfonic Acid → 3-amino-8-bromo-1,5-dimethyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one

HRID 1635118Notes

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

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, 3H), 4.12 (d, 1H, J=1.1 Hz), 3.27 (s, 3H), 2.30 (d, 3H, 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-5560bfa686d54d64b61fbfe9c39d3b57
Source dataset: uspto-grants-2003_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06509333B2

Reaction notes

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