Dichloromethane methanol → Tert-butyl 4-(5-(1-phenylethyl)pyrimidin-2-yl)piperazine-1-carboxylate

HRID 1498833Notes

Reaction equation

HRID 1498833 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[Br-].[C:22]1([CH:28]([Zn+])[CH3:29])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C1(C(C2C=NC(N3CCNCC3)=NC=2)C)C=CC=CC=1.CO.ClCCl>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:22]1([CH:28]([C:2]2[CH:3]=[N:4][C:5]([N:8]3[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]3)=[N:6][CH:7]=2)[CH3:29])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 21226129Dichloromethane methanolHCID 21914476tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylateHCID 1180226145-(1-Phenylethyl)-2-(piperazin-1-yl)pyrimidineHCID 178462437HCID 178462437, compound

Product 1

HCID 118022835Tert-butyl 4-(5-(1-phenylethyl)pyrimidin-2-yl)piperazine-1-carboxylateYield 23%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

To a solution of tert-butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate (4.1 g, 12.0 mmol) and tetrakis(triphenylphosphine)palladium (708 mg, 1.0 mmol) in THF (80 mL, dry) was added dropwise a solution of (1-phenylethyl)zinc(II) bromide in THF (20 mL, 1 M, 20 mmol) under nitrogen atmosphere, and the mixture was stirred at 70° C. overnight. The reaction mixture was cooled to RT and filtered through a pad of Celite. The filtration was concentrated and purified by silica gel chromatography to give tert-butyl 4-(5-(1-phenylethyl)pyrimidin-2-yl)piperazine-1-carboxylate (1.0 g, yield 23%) as a white solid (ethyl acetate/petroleum ether=1/5 as elute) and 5-(1-phenylethyl)-2-(piperazin-1-yl)pyrimidine (2.4 g, 75%) as a yellow oil (methanol/dichloromethane=1/20 as elute). MS (ES+) C16H20N4 requires: 268. found: 269 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. filtrationfiltered through a pad of Celite
  3. filtrationThe filtration
  4. concentrationwas concentrated
  5. custompurified by silica gel chromatography
  6. customto give

Sources & evidence

ORD record
ord-8c43f5014e754d1e87d145eb16874357
Source dataset
uspto-grants-2015_12
Patent number
US09200002B2

Reaction notes

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