Cesium carbonate → Ethyl 4-methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxylate

HRID 517540Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 517540
Br[C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[S:10][C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:8][C:7]=1[CH3:16].[CH3:20][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:16][C:7]1[N:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[S:10][C:6]=1[CH2:5][C:4]1[CH:17]=[CH:18][CH:19]=[C:2]([N:24]2[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]2)[CH:3]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86711480Ethyl 5-(3-bromobenzyl)-4-methylthiazole-2-carboxylate

Produkt 1

HCID 86711481Ethyl 4-methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxylateAusbeute 75,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Versuchsvorschrift

A mixture of ethyl 5-(3-bromobenzyl)-4-methylthiazole-2-carboxylate (340 mg, 1.0 mmol), 1-methylpiperazine (0.2 mL, 2 mmol) and Cs2CO3 (652 mg, 2 mmol) in toluene (5 mL) was degassed (argon bubbling for 5 min), tris(dibenzylideneacetone)dipalladium(0) (46 mg, 0.05 mmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (48 mg, 0.1 mmol) were quickly added. The reaction mixture was refluxed overnight, cooled to RT, then quenched with H2O and extracted with EtOAc (3×30 mL). The organic layers were washed with H2O (30 mL) and brine (10 mL), dried over Na2SO4, filtered, and concentrated to afford the crude product, which was purified by silica gel column chromatography (DCM:MeOH=20:1) to give ethyl 4-methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxylate as a yellow solid (270 mg, 75%). MS (ES+) C19H25N3O2S requires: 359, found: 360[M+H]+.

Aufarbeitung

  1. additionwere quickly added
  2. temperatureThe reaction mixture was refluxed overnight
  3. customquenched with H2O
  4. extractionextracted with EtOAc (3×30 mL)
  5. washThe organic layers were washed with H2O (30 mL) and brine (10 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford the crude product, which
  10. customwas purified by silica gel column chromatography (DCM:MeOH=20:1)

Quellen und Nachweise

ORD-Eintrag
ord-9d61ffea345d46baaee30779355c8b5e
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115120B2

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