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

HRID 430666ノート

反応式

HRID 430666 の反応式
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

参加物

5

反応物 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

生成物 1

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

反応条件

温度
7.5 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-bcbc7737d6224e01bc305d2ccbe7d23e
出典データセット
uspto-grants-2001_11
特許番号
US06323197B1

反応ノート

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