Water → 3-chloro-6-(4-piperidyl)-11H-benzo[b][1,4]benzodiazepine

HRID 2109896Notes

Reaction equation

HRID 2109896 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11](Cl)[C:10]3[CH:13]=[CH:14][CH:15]=[CH:16][C:9]=3[CH:8]=[N:7][C:6]=2[CH:17]=1.B(Br)(Br)Br.CC[N:24]([CH2:27][CH3:28])[CH2:25][CH3:26].O.[CH2:30]1COCC1>C(Cl)Cl.[I-].C(C1CCN([Zn+])CC1)(OCC1C=CC=CC=1)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3[CH:13]=[CH:14][CH:15]=[CH:16][C:9]=3[C:8]([CH:30]3[CH2:26][CH2:25][NH:24][CH2:27][CH2:28]3)=[N:7][C:6]=2[CH:17]=1

Participants

10

Reactant 5

HCID 962WaterHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 25134Boron tribromideHCID 574854318,5-Dichloro-5H-dibenzo[b,e][1,4]diazepine

Product 1

HCID 1356206833-chloro-6-(4-piperidyl)-11H-benzo[b][1,4]benzodiazepine

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 178525046HCID 178525046, compoundCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

4-CBZ-piperidylzinc iodide (generated from of 4-CBZ-piperidyl iodide (345 mg, 1.0 mmol) using zinc metal and dibromoethane) (0.8 mmol) was added at 50° C. to a solution of 8,5-dichloro-5H-dibenzo[b,e][1,4]diazepine (160FE64) (106 mg, 0.4 mmol) and PdCl2(PPh3)2 (18 mg, 0.04 mmol) in dry THF (2 ml). The reaction was shaken for 16 h and then quenched by the addition of aqueous saturated NH4Cl-solution. The resulting mixture was extracted twice with ether and the combined ethereal phases were washed with brine and dried (Na2SO4). Filtration followed by concentration at reduced pressure of the organic phase gave a crude product. BBr3 (100 μl) added at −30° C. was added to the crude product dissolved in CH2Cl2 (1 ml). The reaction temperature was then slowly increased to 0° C. TLC indicated complete conversion of the starting material and Et3N, H2O and EtOAc were sequentially added to the reaction mixture. The organic phase was washed with brine and dried (Na2SO4). Filtration followed by concentration at reduced pressure gave a crude product, which was purified by HPLC to give 2.3 mg of the title compound (160FE67A). MS (ESI) 312 (MH+). Purity for MH+ (UV/MS) 99/96.

Workup

  1. customquenched by the addition of aqueous saturated NH4Cl-solution
  2. extractionThe resulting mixture was extracted twice with ether
  3. washthe combined ethereal phases were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationFiltration
  6. concentrationfollowed by concentration at reduced pressure of the organic phase
  7. customgave a crude product
  8. additionwere sequentially added to the reaction mixture
  9. washThe organic phase was washed with brine
  10. dry with materialdried (Na2SO4)
  11. filtrationFiltration
  12. concentrationfollowed by concentration at reduced pressure
  13. customgave a crude product, which
  14. customwas purified by HPLC

Sources & evidence

ORD record
ord-c3be6b0593e24585b0132fa1b39da681
Source dataset
uspto-grants-2009_04
Patent number
US07517871B2

Reaction notes

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