(S)-2-(2-Methoxyethyl)piperazine → (S)-6,7-Difluoro-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene

HRID 131452

반응식

HRID 131452 반응식
Cl.[F:2][C:3]1[C:4]([F:19])=[CH:5][C:6]2[N:15]=[C:14]([NH2:16])[C:13]3[CH:12]=[C:11]([CH3:17])[S:10][C:9]=3[NH:8][C:7]=2[CH:18]=1.[CH3:20][O:21][CH2:22][CH2:23][C@H:24]1[CH2:29]N[CH2:27][CH2:26][NH:25]1>CS(C)=O.C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[F:2][C:3]1[C:4]([F:19])=[CH:5][C:6]2[N:15]=[C:14]([N:16]3[CH2:27][CH2:26][NH:25][C@@H:24]([CH2:23][CH2:22][O:21][CH3:20])[CH2:29]3)[C:13]3[CH:12]=[C:11]([CH3:17])[S:10][C:9]=3[NH:8][C:7]=2[CH:18]=1

참가 물질

6

반응물 2

HCID 55287560(S)-2-(2-Methoxyethyl)piperazineHCID 1363885776,7-Difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride

생성물 1

HCID 135434034(S)-6,7-Difluoro-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene수율 38%

시약·촉매·용매 3

HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 22340214Dimethylsulfoxide toluene용매

반응 조건

온도
130 °C

실험 절차

Dissolve 6,7-difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride (1.7 g, 5.66 mmol) and (S)-2-(2-methoxy-ethyl)-piperazine (2.45 g, 17.0 mmol) in dimethylsulfoxide/toluene (1:2)(21 ml), stir under nitrogen and heat in an oil bath at 130° C. for 43 hours. Cool to ambient temperature. Dilute the mixture with one volume water and two volumes ethyl acetate, separate layers and extract the aqueous layer with ethyl acetate. Basify the aqueous layer with ammonium hydroxide and extract with ethyl acetate. Combine all ethyl acetate extracts and wash with water and brine. Dry the organic phase (Na2SO4), filter and concentrate under reduced pressure. Purify by silica gel chromatography (eluent: 0-10% 2N ammonia in methanol/dichloromethane) to give the title compound (840 mg, 38%): Mass Spectrum (ESMS) 393 (M+1); 391 (M−1).

후처리

  1. temperatureCool to ambient temperature
  2. customseparate layers
  3. extractionextract the aqueous layer with ethyl acetate
  4. extractionextract with ethyl acetate
  5. washwash with water and brine
  6. dry with materialDry the organic phase (Na2SO4)
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. customPurify by silica gel chromatography (eluent: 0-10% 2N ammonia in methanol/dichloromethane)

출처 및 근거

ORD 기록
ord-bfd5740c595d4999a47808bba67d417e
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07384934B2

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