tert-Butyl 4-carbamothioylpiperazine-1-carboxylate → 4-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-2-(piperazin-1-yl)thiazole

HRID 1930027Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1930027
Br[CH:2]([C:13]1[CH:14]=[CH:15][C:16]2[N:17]([C:19]([CH:22]([CH3:24])[CH3:23])=[N:20][N:21]=2)[N:18]=1)[C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[F:12])=O.[C:25]([N:28]1[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]1)(=[S:27])[NH2:26]>CCO>[F:12][C:6]1[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]=1[C:3]1[N:26]=[C:25]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[S:27][C:2]=1[C:13]1[CH:14]=[CH:15][C:16]2[N:17]([C:19]([CH:22]([CH3:24])[CH3:23])=[N:20][N:21]=2)[N:18]=1

Komponenten

4

Edukt 2

HCID 12093220tert-Butyl 4-carbamothioylpiperazine-1-carboxylateHCID 579298612-Bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone

Produkt 1

HCID 579299074-(2,4-Difluorophenyl)-5-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-2-(piperazin-1-yl)thiazoleAusbeute 10 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Versuchsvorschrift

A mixture of 2-bromo-1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (0.61 g, 1.5 mmol; Preparation #A.2) and tert-butyl 4-carbamothioylpiperazine-1-carboxylate (Beta Pharma Inc, 0.341 g, 1.39 mmol) in EtOH (3 mL) was heated to reflux overnight. After cooling to ambient temperature, the crude mixture was partitioned between DCM and 1N aqueous HCl. The aqueous layer was basified with saturated aqueous Na2CO3 and extracted with DCM. The organics were dried over MgSO4, filtered, concentrated under reduced pressure, and purified by silica gel chromatography using DCM/MeOH (linear gradient, 100:0 to 90:10) to give the title compound (0.061 g, 10%): LC/MS (Table 1, Method a) Rt=2.31 min; MS m/z: 442.8 (M+H)+.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureto reflux overnight
  3. customthe crude mixture was partitioned between DCM and 1N aqueous HCl
  4. extractionextracted with DCM
  5. dry with materialThe organics were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. custompurified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-98f1b5fe6d5f4c929f8174b44a61e009
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08188083B2

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