Cesium carbonate → HCID 86711918, compound

HRID 1475224Notes

Reaction equation

HRID 1475224 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[CH2:5][N:6]1[C:10]([CH3:11])=[N:9][C:8]([C:12]#[N:13])=[N:7]1.[CH3:17][N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]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]>[CH3:11][C:10]1[N:6]([CH2:5][C:4]2[CH:14]=[CH:15][CH:16]=[C:2]([N:21]3[CH2:22][CH2:23][N:18]([CH3:17])[CH2:19][CH2:20]3)[CH:3]=2)[N:7]=[C:8]([C:12]#[N:13])[N:9]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86711917HCID 86711917, compound

Product 1

HCID 86711918HCID 86711918, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-(3-bromobenzyl)-5-methyl-1H-1,2,4-triazole-3-carbonitrile (198 mg, 0.71 mmol), 1-methylpiperazine (159 μL, 1.4 mmol), Cs2CO3 (466 mg, 1.4 mmol), dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (34 mg, 0.07 mmol) and tris(dibenzylideneacetone)dipalladium(0) (65.4 mg, 0.07 mmol) in toluene (3.5 mL) was degassed (freeze-pump-thaw, under N2). The reaction mixture was stirred at 100° C. overnight before being quenched with H2O (5 mL), taken up in EtOAc (15 mL), washed with H2O (3×10 mL), brine (2×10 mL), dried with Na2SO4 and concentrated under reduced pressure. The crude product was purified on a Biotage pre-packed silica gel column with a gradient of 0% to 10% MeOH:DCM to afford 5-methyl-1-(3-(4-methylpiperazin-1-yl)benzyl)-1H-1,2,4-triazole-3-carbonitrile (120 mg, 57%) as a white solid. MS (ES+) C16H20N6 requires: 296 found: 297 [M+H]+.

Workup

  1. customwas degassed (freeze-pump-thaw, under N2)
  2. custombefore being quenched with H2O (5 mL)
  3. washwashed with H2O (3×10 mL), brine (2×10 mL)
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified on a Biotage pre-packed silica gel column with a gradient of 0% to 10% MeOH

Sources & evidence

ORD record
ord-218148b0809a4e9a88a7e61a5b0b8376
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

Loading…