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

HRID 1359583노트

반응식

HRID 1359583 반응식
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

참가 물질

5

반응물 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

생성물 1

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

반응 조건

온도
7.5 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-f3f38f0e420c4ed6b747220d55e097fb
출처 데이터셋
uspto-grants-2003_07
특허 번호
US06600036B2

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