Potassium Carbonate → 2-(4-(5-Bromo-2-methyl-2,3-dihydrobenzofuran-2-yl)piperidin-1-yl)-5-cyclopropylpyrimidine

HRID 1025511Notes

Reaction equation

HRID 1025511 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([CH:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)([CH3:10])[CH2:7][C:6]=2[CH:17]=1.Cl[C:19]1[N:24]=[CH:23][C:22]([CH:25]2[CH2:27][CH2:26]2)=[CH:21][N:20]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([CH:11]3[CH2:16][CH2:15][N:14]([C:19]4[N:24]=[CH:23][C:22]([CH:25]5[CH2:27][CH2:26]5)=[CH:21][N:20]=4)[CH2:13][CH2:12]3)([CH3:10])[CH2:7][C:6]=2[CH:17]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 468640872-Chloro-5-cyclopropylpyrimidineHCID 674657574-(5-Bromo-2-methyl-2,3-dihydrobenzofuran-2-yl)piperidine

Product 1

HCID 674689412-(4-(5-Bromo-2-methyl-2,3-dihydrobenzofuran-2-yl)piperidin-1-yl)-5-cyclopropylpyrimidineYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-(5-bromo-2-methyl-2,3-dihydrobenzofuran-2-yl)piperidine (0.3 g, 1.013 mmol), 2-chloro-5-cyclopropylpyrimidine (0.204 g, 1.317 mmol) and K2CO3 (0.42 g, 3.04 mmol) in DMF (5 mL) was heated in 90° C. oil bath overnight. At the conclusion of this period, the reaction mixture was cooled to room temperature, quenched with H2O (5 mL), and then extracted with EtOAc (3×5 mL). The combined organic layers were washed with H2O (3×5 mL) and brine (5 mL). The organic layer was separated, dried (Na2SO4), filtered, and concentrated to yield a residue. The residue was purified by column chromatography (silica gel, hexanes/EtOAc gradient 0 to 35% EtOAc) to afford Compound 11E as white solid (0.315 g, 31% yield). LC/MS (m/z)=414 (M+H)+.

Workup

  1. temperatureAt the conclusion of this period, the reaction mixture was cooled to room temperature
  2. customquenched with H2O (5 mL)
  3. extractionextracted with EtOAc (3×5 mL)
  4. washThe combined organic layers were washed with H2O (3×5 mL) and brine (5 mL)
  5. customThe organic layer was separated
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield a residue
  10. customThe residue was purified by column chromatography (silica gel, hexanes/EtOAc gradient 0 to 35% EtOAc)

Sources & evidence

ORD record
ord-20c0920ef20d422784b892a7d5a6b35c
Source dataset
uspto-grants-2014_05
Patent number
US08729084B2

Reaction notes

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