Hydrogen Bromide → 3-Amino-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one

HRID 482339Notes

Reaction equation

HRID 482339 reaction equation
C(OC([NH:11][CH:12]1[C:18](=[O:19])[NH:17][C:16]2[CH:20]=[CH:21][CH:22]=[CH:23][C:15]=2[C:14]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[N:13]1)=O)C1C=CC=CC=1.Br>C(O)(=O)C.C(OCC)C>[NH2:11][CH:12]1[C:18](=[O:19])[NH:17][C:16]2[CH:20]=[CH:21][CH:22]=[CH:23][C:15]=2[C:14]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[N:13]1

Participants

5

Reactant 2

HCID 260Hydrogen BromideHCID 2756242Benzyl (2-oxo-5-phenyl-2,3-dihydro-1h-benzo[e][1,4]diazepin-3-yl)carbamate

Product 1

HCID 42596493-Amino-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 3-[(benzyloxycarbonyl)amino]-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one (7.00 g, 18.2 mmol) in glacial acetic acid (200 mL), prepared as in Intermediate 6, is saturated with HBr gas. The reaction is warmed to 70° C. and held for 20 min. The temperature is raised to 80° C. and maintained for an additional 20 min. The resulting slurry is cooled to ambient temperature, diluted with anhydrous diethyl ether (200 ml), agitated for 0.5 hrs., filtered and washed with diethyl ether. The hydrobromide salt is dried at 60° C. under vacuum to provide the dihydrobromide salt (6.836 g, 16.5 mmol) of the title compound. The free base is obtained by partitioning the dihydrobromide (6.100 g, 14.3 mmol) between aqueous potassium carbonate (5% w/v, 50 mL) and a mixture of ethyl acetate, isopropanol and DCM. After separating the phases, the organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to a solid. The product is dried under high vacuum to provide the title compound as a crystalline solid (3.69 g, 14.3 mmol). 1H NMR (300 MHz, d6-DMSO) δ=4.21 (s, 1H); 7.15-7.60 (m, 9H); 10.66 (s, 1H). TLC: Rf =0.33 (95:5 chloroform: methanol).

Workup

  1. temperatureThe temperature is raised to 80° C.
  2. temperaturemaintained for an additional 20 min
  3. temperatureThe resulting slurry is cooled to ambient temperature
  4. filtration, filtered
  5. washwashed with diethyl ether
  6. dry with materialThe hydrobromide salt is dried at 60° C. under vacuum

Sources & evidence

ORD record
ord-e8722bef2b774236b72952e526a12964
Source dataset
uspto-grants-1998_08
Patent number
US05795887

Reaction notes

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