Bromine → 7-Bromo-3-methyl-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one

HRID 75262

Reaction equation

HRID 75262 reaction equation
[CH3:1][CH:2]1[C:8](=[O:9])[NH:7][C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[N:3]1.[Br:20]Br>C(O)(=O)C.S(=O)(=O)(O)O>[Br:20][C:12]1[CH:11]=[CH:10][C:6]2[NH:7][C:8](=[O:9])[CH:2]([CH3:1])[N:3]=[C:4]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:5]=2[CH:13]=1

Participants

5

Reactant 2

HCID 24408BromineHCID 110322973-Methyl-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one2×

Product 1

HCID 6255777-Bromo-3-methyl-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-oneYield 79%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 1118Sulfuric AcidSolvent

Procedure

To a stirred solution of 131 (66.5 g, 265 m mol) in glacial acetic acid (400 mL), sulfuric acid (80 mL) was added to the solution. Bromine (28 mL, 530 mmol) dissolved in acetic acid (150 mL) was added dropwise into the mixture. The reaction mixture was allowed to stir until analysis by NMR spectroscopy indicated that all of the starting material 131 had been consumed. The solution was concentrated under reduced pressure and then brought to pH 7 by addition of 1N aq NaOH solution and then extracted with EtOAc. The crude product 132 was purified by recrystallization from CH2Cl2 to afford 132 (68.66 g, 79%). mp 210-212° C.; IR (KBr, cm−1) 2931, 1692, 1603, 1563, 1475, 1445, 1375, 1259, 1235, 1130, 1090; 1H NMR (CDCl3) δ 9.36 (s, 1 H), 7.63 (dd, J=2.22, 8.58 Hz, 1 H), 7.54-7.39 (m, 6 H), 7.12 (d, J=8.61 1 H), 3.76 (q, J=6.3 Hz, 1 H), 1.76 (d, J=6.45 Hz, 3 H). MS (EI) m/e (relative intensity) 330 (M++1, 21), 329 (M+, 50), 328 (22), 327 (48), 289 (44), 288 (46), 287 (100), 286 (45), 285 (60), 205 (25), 77 (49).

Workup

  1. additionwas added dropwise into the mixture
  2. customhad been consumed
  3. concentrationThe solution was concentrated under reduced pressure
  4. additionbrought to pH 7 by addition of 1N aq NaOH solution
  5. extractionextracted with EtOAc
  6. customThe crude product 132 was purified by recrystallization from CH2Cl2

Sources & evidence

ORD record
ord-cdc748ea319c451e82f9b532bb976812
Source dataset
uspto-grants-2014_09
Patent number
US08835424B2

Linked notes

Loading…