Stannous Chloride → 5-(4-fluorophenyl)-8-methyl-11H-1,3-dioxolo[4,5-h]imidazo[1,2-c][2,3]benzodiazepine

HRID 430666Notes

Reaction equation

HRID 430666 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]4[O:21][CH2:20][O:19][C:17]4=[CH:18][C:13]=3[CH2:12][C:11]3=[N:22][CH:23]=[C:24]([CH3:25])[N:10]3[N:9]=2)=[CH:4][CH:3]=1.N([O-])=O.[Na+].[Sn](Cl)Cl.CCCC[N+](CCCC)(CCCC)CCCC.[FH:50].F.[F-]>>[F:50][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]4[O:21][CH2:20][O:19][C:17]4=[CH:18][C:13]=3[CH2:12][C:11]3=[N:22][CH:23]=[C:24]([CH3:25])[N:10]3[N:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 24479Stannous ChlorideHCID 11748636N,N,N-Tributylbutan-1-aminium fluoride--hydrogen fluoride (1/1/2)HCID 181831705-(4-aminophenyl)-8-methyl-11H-1,3-dioxolo[4,5-h]imidazo[1,2-c][2,3]benzodiazepineHCID 23668193Sodium Nitrite

Product 1

HCID 181831775-(4-fluorophenyl)-8-methyl-11H-1,3-dioxolo[4,5-h]imidazo[1,2-c][2,3]benzodiazepineYield 52.5%

Conditions

Temperature
7.5 °C

Procedure

First 200 mg of 5-(4-aminophenyl)-8-methyl-11H-1,3-dioxolo[4,5-h]imidazo[1,2-c][2,3]benzodiazepine is added to a solution of 6 ml of hydrogen fluoride-pyridine complex (1:1) under argon, and then 51 mg of sodium nitrite is added at 0-5° C. After stirring at 5-10° C. for 40 minutes, 117 mg of tin(II) chloride and 190 mg of tetrabutylammonium dihydrogen trifluoride are added to the preparation. It is then heated for 3 hours to a bath temperature of 100° C. After cooling, it is added to ice water and extracted three times with ethyl acetate and three times with methylene chloride. The collected organic phase is dried, filtered, concentrated by evaporation and chromatographed on silica gel first with methylene chloride:ethanol=10:1, then a second time with acetone:ethyl acetate=3:1 and then a third time with methylene chloride:ethanol=95:5. 106 mg of 5-(4-fluorophenyl)-8-methyl-11H-1,3-dioxolo[4,5-h]imidazo[1,2-c][2,3]benzodiazepine with a melting point of 190° C. is obtained.

Workup

  1. temperatureIt is then heated for 3 hours to a bath temperature of 100° C
  2. temperatureAfter cooling
  3. extractionextracted three times with ethyl acetate and three times with methylene chloride
  4. customThe collected organic phase is dried
  5. filtrationfiltered
  6. concentrationconcentrated by evaporation
  7. customchromatographed on silica gel first with methylene chloride

Sources & evidence

ORD record
ord-bcbc7737d6224e01bc305d2ccbe7d23e
Source dataset
uspto-grants-2001_11
Patent number
US06323197B1

Reaction notes

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