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

HRID 517540Notes

Reaction equation

HRID 517540 reaction equation
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

Participants

7

Reactant 4

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

Product 1

HCID 86711481Ethyl 4-methyl-5-(3-(4-methylpiperazin-1-yl)benzyl)thiazole-2-carboxylateYield 75.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

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]+.

Workup

  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)

Sources & evidence

ORD record
ord-9d61ffea345d46baaee30779355c8b5e
Source dataset
uspto-grants-2015_08
Patent number
US09115120B2

Reaction notes

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