Hydrochloric Acid → 8-Chloro-5-methyl-11-(piperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine

NaH (12 mg, 0.29 mmol, 60% in mineral oil) was added to a mixture of 8,5-dichloro-5H-dibenzo[b,e][1,4]diazepine (160FE64) (50 mg, 0.19 mmol) in toluene (1.5 mL) and DMF (0.5 mL). MeI (24 μL, 0.38 mmol) was then added. The resulting mixture was stirred for 1 h then quenched by addition of saturated aqueous NaHCO3-solution (2 mL). The mixture was extracted with diethyl ether, and the combined organic phases were dried (Na2SO4) and concentrated. The residue was taken up in toluene (2.0 mL), piperazine (98 mg, 1.1 mmol) was added, and the resulting mixture was stirred at 100° C. for 1 h. Aqueous HCl (1 mL, 2M) and EtOAc (2 mL) was then added to the mixture. The phases were separated and the aqueous phase was extracted with EtOAc (2 mL) and then aqueous NaOH (2 mL, 2 M) was added. The basic aqueous phase was extracted with EtOAc (3×2 mL) and the combined organic phases were dried (Na2SO4) and concentrated. The residue was dissolved in DMF and purified on HPLC to give 34 mg of the title compound (189JO25A). MS (ESI) 327 (MH+). Purity for MH+ (UV/MS) 100/100.

1. customthen quenched by addition of saturated aqueous NaHCO3-solution (2 mL)
2. extractionThe mixture was extracted with diethyl ether
3. dry with materialthe combined organic phases were dried (Na2SO4)
4. concentrationconcentrated
5. stirringthe resulting mixture was stirred at 100° C. for 1 h
6. customThe phases were separated
7. extractionthe aqueous phase was extracted with EtOAc (2 mL)
8. additionaqueous NaOH (2 mL, 2 M) was added
9. extractionThe basic aqueous phase was extracted with EtOAc (3×2 mL)
10. dry with materialthe combined organic phases were dried (Na2SO4)
11. concentrationconcentrated
12. dissolutionThe residue was dissolved in DMF
13. custompurified on HPLC

ORD record

ord-18139bd642ec4ed5ba9a4136975baf1e

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07550454B2