Diisopropylethylamine → (S)-5-[3-(2-Methoxy-ethyl)-piperazin-1-yl]-8-trifluoromethyl-11H-12-thia-6,11-diaza-dibenzo[a,f]azulene

HRID 131513

반응식

HRID 131513 반응식
Cl.[F:2][C:3]([F:24])([F:23])[C:4]1[CH:22]=[CH:21][C:7]2[NH:8][C:9]3[S:10][C:11]4[CH:20]=[CH:19][CH:18]=[CH:17][C:12]=4[C:13]=3[C:14]([NH2:16])=[N:15][C:6]=2[CH:5]=1.[CH3:25][O:26][CH2:27][CH2:28][C@H:29]1[CH2:34]N[CH2:32][CH2:31][NH:30]1.C(N(C(C)C)CC)(C)C>CS(C)=O.C1(C)C=CC=CC=1.C(OCC)(=O)C.[OH-].[Na+]>[CH3:25][O:26][CH2:27][CH2:28][C@@H:29]1[NH:30][CH2:31][CH2:32][N:16]([C:14]2[C:13]3[C:12]4[CH:17]=[CH:18][CH:19]=[CH:20][C:11]=4[S:10][C:9]=3[NH:8][C:7]3[CH:21]=[CH:22][C:4]([C:3]([F:2])([F:23])[F:24])=[CH:5][C:6]=3[N:15]=2)[CH2:34]1

참가 물질

7

반응물 3

HCID 81531DiisopropylethylamineHCID 55287560(S)-2-(2-Methoxyethyl)piperazineHCID 1363885748-Trifluoromethyl-11H-12-thia-6,11-diaza-dibenzo[a,f]azulen-5-ylamine hydrochloride

생성물 1

HCID 135507279(S)-5-[3-(2-Methoxy-ethyl)-piperazin-1-yl]-8-trifluoromethyl-11H-12-thia-6,11-diaza-dibenzo[a,f]azulene수율 35.9%

시약·촉매·용매 3

HCID 8857Ethyl Acetate용매HCID 14798Sodium Hydroxide용매HCID 22340214Dimethylsulfoxide toluene용매

실험 절차

Add 8-trifluoromethyl-11H-12-thia-6,11-diaza-dibenzo[a,f]azulen-5-ylamine hydrochloride (0.75 g, 2.0 mmol) to a solution of (S)-2-(2-methoxy-ethyl)-piperazine (0.58 g, 4.1 mmol) in dimethyl sulfoxide: toluene (1:8, 0.2M). Add diisopropylethylamine (1 equiv), heat to 110° C., and stir. After 45 hours, cool to ambient temperature, and dilute with ethyl acetate and 0.1 N NaOH. Separate the aqueous layer and extract it with ethyl acetate (3×). Wash all organics with a saturated solution of sodium chloride, and then dry (sodium sulfate), filter, and concentrate them under reduced pressure. Purify the oil by flash chromatography, eluting with a gradient of a 3% solution of 2M ammonia in methanol, in dichloromethane (0-100% in dichloromethane). Reconstitute the material in ethyl acetate and wash it with a saturated solution of sodium chloride (2×) to remove residual dimethylsulfoxide. Back extract the combined aqueous layers with ethyl acetate. Dry (sodium sulfate) the organic phases, filter, and concentrate them under reduced pressure to give the title compound (0.331 g). Mass spectrum (APCI+, m/e): 461 (M+1).

후처리

  1. customSeparate the aqueous layer
  2. extractionextract it with ethyl acetate (3×)
  3. washWash all organics with a saturated solution of sodium chloride
  4. dry with materialdry (sodium sulfate)
  5. filtrationfilter
  6. concentrationconcentrate them under reduced pressure
  7. customPurify the oil by flash chromatography
  8. washeluting with a gradient of a 3% solution of 2M ammonia in methanol, in dichloromethane (0-100% in dichloromethane)
  9. washwash it with a saturated solution of sodium chloride (2×)
  10. customto remove residual dimethylsulfoxide
  11. extractionBack extract the combined aqueous layers with ethyl acetate
  12. dry with materialDry (sodium sulfate) the organic phases
  13. filtrationfilter
  14. concentrationconcentrate them under reduced pressure

출처 및 근거

ORD 기록
ord-d115a17f1cc54945b2f705fac539b7de
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07384934B2

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