Diisopropylethylamine → (S)-2-[4-(6,7-Difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-yl)-piperazin-2-yl]-ethanol

HRID 131454

Reaktionsgleichung

Reaktionsgleichung von HRID 131454
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.C(N(CC)C(C)C)(C)C.[NH:29]1[CH2:34][CH2:33]N[CH2:31][C@@H:30]1[CH2:35][CH2:36][OH:37]>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[CH2:33][CH2:34][NH:29][C@@H:30]([CH2:35][CH2:36][OH:37])[CH2:31]3)[C:13]3[CH:12]=[C:11]([CH3:17])[S:10][C:9]=3[NH:8][C:7]=2[CH:18]=1

Komponenten

7

Edukt 3

HCID 81531DiisopropylethylamineHCID 1519380(S)-2-(Piperazin-2-yl)ethanolHCID 1363885776,7-Difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride

Produkt 1

HCID 135401139(S)-2-[4-(6,7-Difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-yl)-piperazin-2-yl]-ethanolAusbeute 41,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 22340214Dimethylsulfoxide tolueneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

Dissolve 6,7-difluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride (1.51, 4.99 mmol), N,N-diisopropylethylamine (0.91 mL, 5.24 mmol) and (S)-2-piperazin-2-yl-ethanol (1.3 g, 9.99 mmol) in dimethylsulfoxide/toluene (1:2)(18 ml), stir under nitrogen and heat in an oil bath at 120° C. for 72 hours. Dilute the mixture with water (20 mL) and ethyl acetate (40 mL), separate layers and extract the aqueous 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: 0-13% 2N ammonia in methanol/dichloromethane) to give 780 mg of impure product. Purify by silica gel chromatography (eluent: 85% dichloromethane/10% acetonitrile/0%2N ammonia in methanol to 80% dichloromethane/10% acetonitrile/10% 2N ammonia in methanol) to give the title compound (516 mg, 27%): Mass Spectrum (ESMS) 379 (M+1); 377 (M−1).

Aufarbeitung

  1. customseparate layers
  2. extractionextract the aqueous with ethyl acetate
  3. washwash with water and brine
  4. dry with materialDry the organic phase (Na2SO4)
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure
  7. customPurify by silica gel chromatography (eluent: 0-13% 2N ammonia in methanol/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-056780a3f2694141babfa2992ca66ad9
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07384934B2

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