p-Bromobenzenesulfonyl chloride → 10-[(4-Bromophenyl)sulfonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine

HRID 2244259Notes

Reaction equation

HRID 2244259 reaction equation
[CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[NH:7][CH2:6][C:5]=12.C(N(CC)C(C)C)(C)C.[Br:24][C:25]1[CH:30]=[CH:29][C:28]([S:31](Cl)(=[O:33])=[O:32])=[CH:27][CH:26]=1>ClCCl>[Br:24][C:25]1[CH:30]=[CH:29][C:28]([S:31]([N:7]2[C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=3[CH2:10][N:4]3[CH:3]=[CH:2][CH:1]=[C:5]3[CH2:6]2)(=[O:33])=[O:32])=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 7396p-Bromobenzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 1554704810,11-Dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine

Product 1

HCID 6868787110-[(4-Bromophenyl)sulfonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepineYield 109.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (10 g, 0.0543 mol) and N,N-diisopropylethylamine (14.2 mL, 0.0814 mol) in dry dichloromethane (200 mL) at 0° C. under nitrogen was added dropwise a solution of 4-bromobenzenesulfonyl chloride (10.4 g, 0.0407 mol) in dry dichloromethane (80 mL) over 10 minutes. The ice bath was removed and the reaction mixture stirred at room temperature for 18 hours. The reaction mixture was then washed with 1 M hydrochloric acid (2×250 mL), 0.5 M sodium hydroxide (250 mL) and water (250 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo to afford a purple syrup (17.91 g). Purification by flash chromatography using a solvent gradient of 5 to 10% ethyl acetate in hexane afforded a tan solid (3.21 g) that was recrystallized from ethyl acetate/hexane to afford the title compound (2.55 g, 16%) as a tan crystalline solid, m.p. 128-129° C.

Workup

  1. customThe ice bath was removed
  2. washThe reaction mixture was then washed with 1 M hydrochloric acid (2×250 mL), 0.5 M sodium hydroxide (250 mL) and water (250 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-39cd27c420a144268851fa22c3f8ffa8
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

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