Sodium Iodide → 1-(2,2,4,6,7-Pentamethyl-2,3-dihydro-1-benzofuran-5-yl)-4-(1,3,5-trimethyl-1H-pyrazole-4-yl)piperazine

HRID 1850498Notes

Reaction equation

HRID 1850498 reaction equation
Cl[CH2:2][CH2:3][N:4]([CH2:19][CH2:20]Cl)[C:5]1[C:6]([CH3:18])=[C:7]([CH3:17])[C:8]2[O:12][C:11]([CH3:14])([CH3:13])[CH2:10][C:9]=2[C:15]=1[CH3:16].[CH3:22][N:23]1[C:27]([CH3:28])=[C:26]([NH2:29])[C:25]([CH3:30])=[N:24]1.C(=O)([O-])O.[Na+].[I-].[Na+]>C(OCC)(=O)C.CN1CCCC1=O>[CH3:13][C:11]1([CH3:14])[CH2:10][C:9]2[C:15]([CH3:16])=[C:5]([N:4]3[CH2:19][CH2:20][N:29]([C:26]4[C:25]([CH3:30])=[N:24][N:23]([CH3:22])[C:27]=4[CH3:28])[CH2:2][CH2:3]3)[C:6]([CH3:18])=[C:7]([CH3:17])[C:8]=2[O:12]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 1616031,3,5-trimethyl-1H-pyrazol-4-amineHCID 516892Sodium BicarbonateHCID 66760837N,N-bis(2-chloroethyl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-amine

Product 1

HCID 594850091-(2,2,4,6,7-Pentamethyl-2,3-dihydro-1-benzofuran-5-yl)-4-(1,3,5-trimethyl-1H-pyrazole-4-yl)piperazineYield 42%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

To 1-methyl-2-pyrrolidone (5.0 mL) solution of N,N-bis(2-chloroethyl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-amine (660 mg, 2.0 mmol) synthesized in Reference example 146, 1,3,5-trimethyl-1H-pyrazole-4-amine (300 mg, 2.4 mmol), sodium hydrogen carbonate (400 mg, 4.8 mmol) and sodium iodide (300 mg, 2.0 mmol) were added, and stirred at 120° C. for 16 hours. The reaction solution was diluted with ethyl acetate, washed with water and saturated brine, and dried over sodium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate 9:1). The resulting solids were recrystallized from ethanol-water to obtain the title compound 320 mg (yield 42%). Melting point was 162 to 164° C. (ethanol-water).

Workup

  1. additionwere added
  2. washwashed with water and saturated brine
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was removed by distillation under reduced pressure
  5. customthe resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate 9:1)
  6. customThe resulting solids were recrystallized from ethanol-water

Sources & evidence

ORD record
ord-8cf4ffe50cfa492fb2b6897936f74fa3
Source dataset
uspto-grants-2015_02
Patent number
US08957069B2

Reaction notes

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