1-Methylpiperazine → 8-fluoro-12-(4-methylpiperazin-1-yl)-6H-(1)benzothieno(2,3-b)(1,5)benzodiazepine

HRID 1281795노트

반응식

HRID 1281795 반응식
[NH2:1][C:2]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:3]=1[NH:4][C:5]1[S:9][C:8]2[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=2[C:6]=1[C:14](OCC)=O.[CH3:24][N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>C1(OC)C=CC=CC=1.[Ti](Cl)(Cl)(Cl)Cl>[F:23][C:20]1[CH:21]=[CH:22][C:2]2[N:1]=[C:14]([N:28]3[CH2:29][CH2:30][N:25]([CH3:24])[CH2:26][CH2:27]3)[C:6]3[C:7]4[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=4[S:9][C:5]=3[NH:4][C:3]=2[CH:19]=1

참가 물질

5

반응물 2

HCID 531671-MethylpiperazineHCID 18422159Ethyl 2-(2-amino-5-fluoroanilino)benzo[b]thiophene-3-carboxylate

생성물 1

HCID 99131248-fluoro-12-(4-methylpiperazin-1-yl)-6H-(1)benzothieno(2,3-b)(1,5)benzodiazepine

시약·촉매·용매 2

HCID 24193Titanium Tetrachloride촉매HCID 7519Anisole용매

실험 절차

Ethyl 2-(2-amino-5-fluoroanilino)benzo[b]thiophene-3-carboxylate (24.5 g) and 1-methylpiperazine (135 ml) were dissolved in anisole (400 ml), and titanium tetrachloride (21 ml) was added dropwise while stirring the mixture at room temperature. After the completion of the dropwise addition, the mixture was stirred at 140° C. for 17 hours. The reaction mixture was cooled to 80° C. and poured into ice water. The resultant precipitate was filtrated and the filtrate was extracted with ethyl acetate, washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/methanol) and the obtained oily substance (17 g) was dissolved in ethyl acetate (400 ml). Thereto was added a solution of maleic acid (5.9 g) in ethyl acetate (100 ml) and ethanol (20 ml). The precipitated crystals were collected by filtration and recrystallized from ethanol to give 8-fluoro-12-(4-methylpiperazin-1-yl)-6H-[I]benzothieno[2,3-b][1,5]benzodiazepine.1 maleate (10.2 g).

후처리

  1. additionAfter the completion of the dropwise addition
  2. stirringthe mixture was stirred at 140° C. for 17 hours
  3. temperatureThe reaction mixture was cooled to 80° C.
  4. filtrationThe resultant precipitate was filtrated
  5. extractionthe filtrate was extracted with ethyl acetate
  6. washwashed with saturated brine
  7. dry with materialdried over magnesium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (ethyl acetate/methanol)
  10. dissolutionthe obtained oily substance (17 g) was dissolved in ethyl acetate (400 ml)
  11. additionThereto was added a solution of maleic acid (5.9 g) in ethyl acetate (100 ml) and ethanol (20 ml)
  12. filtrationThe precipitated crystals were collected by filtration
  13. customrecrystallized from ethanol

출처 및 근거

ORD 기록
ord-f09cc590e14a49468e8e612ff06292f3
출처 데이터셋
uspto-grants-2002_09
특허 번호
US06455521B1

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