Triethylamine → 5,5-Dimethyl-2-(5-phenylethynyl-pyridin-2-yl)-pyrazolidin-3-one

HRID 240483Notes

Reaction equation

HRID 240483 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12](=[O:13])[CH2:11][C:10]([CH3:15])([CH3:14])[NH:9]2)=[N:6][CH:7]=1.[C:16]1([C:22]#[CH:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(N(CC)CC)C>C1COCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:14][C:10]1([CH3:15])[NH:9][N:8]([C:5]2[CH:4]=[CH:3][C:2]([C:23]#[C:22][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:7][N:6]=2)[C:12](=[O:13])[CH2:11]1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 10821PhenylacetyleneHCID 709266822-(5-Bromo-pyridin-2-yl)-5,5-dimethyl-pyrazolidin-3-one

Product 1

HCID 665769585,5-Dimethyl-2-(5-phenylethynyl-pyridin-2-yl)-pyrazolidin-3-oneYield 45.5%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Bis-(triphenylphosphine)-palladium(II)dichloride (27 mg, 39 μmol, 0.05 equiv.) was dissolved in 2 ml THF. (210 mg, 770 μmol) 2-(5-Bromo-pyridin-2-yl)-5,5-dimethyl-pyrazolidin-3-one (Example 1, step 2) and phenylacetylene (130 mg, 1.24 mmol, 1.6 equiv.) were added at room temperature. Triethylamine (325 μl, 2.33 mmol, 3 equiv.), triphenylphosphine (6 mg, 23.3 μmol, 0.03 equiv.) and copper(I)iodide (4 mg, 23.3 μmol, 0.03 equiv.) were added and the mixture was stirred for 16 hours at 65° C. The reaction mixture was cooled and extracted with saturated NaHCO3 solution and two times with a small volume of dichloromethane. The crude product was purified by flash chromatography by directly loading the dichloromethane layers onto a silica gel column eluting with an ethyl acetate:heptane gradient 0:100 to 100:0. The desired 5,5-dimethyl-2-(5-phenylethynyl-pyridin-2-yl)-pyrazolidin-3-one (102 mg, 45% yield) was obtained as a white solid, MS: m/e=292.1 (M+H+).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with saturated NaHCO3 solution and two times with a small volume of dichloromethane
  3. customThe crude product was purified by flash chromatography
  4. washeluting with an ethyl acetate

Sources & evidence

ORD record
ord-b12d3ddda32941acbb3bc94d5efaef12
Source dataset
uspto-grants-2014_02
Patent number
US08648088B2

Reaction notes

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