Triethylamine → 2-Methanesulfonyl-5-phenylethynyl-pyrimidine

HRID 629233Notes

Reaction equation

HRID 629233 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[N:6][CH:7]=1.[C:12]1([C:18]#[CH:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=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>[CH3:11][S:8]([C:5]1[N:4]=[CH:3][C:2]([C:19]#[C:18][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:7][N:6]=1)(=[O:10])=[O:9]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 10821PhenylacetyleneHCID 3192865-Bromo-2-(methylsulphonyl)pyrimidine

Product 1

HCID 575167582-Methanesulfonyl-5-phenylethynyl-pyrimidineYield 57%

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 (1.48 g, 2.11 mmol, 0.05 equiv.) was dissolved in 200 ml THF. (10 g, 42.2 mmol) 5-Bromo-2-(methylsulfonyl)pyrimidine and phenylacetylene (9.26 ml, 84.4 mmol, 2 equiv.) were added at room temperature. Triethylamine (17.6 ml, 127 mmol, 3 equiv.), triphenylphosphine (330 mg, 1.3 mmol, 0.03 equiv.) and copper(I)iodide (80 mg, 420 μmol, 0.01 equiv.) were added and the mixture was stirred for 4 hours at 65° C. The reaction mixture was cooled and extracted with saturated NaHCO3 solution and two times with EtOAc. The organic layers were extracted with water, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography on a silica gel column and eluting with an ethyl acetate:heptane gradient 0:100 to 100:0. The desired 2-methanesulfonyl-5-phenylethynyl-pyrimidine (6.2 g, 57% yield) was obtained as a yellow solid, MS: m/e=259.1 (M+H+).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with saturated NaHCO3 solution and two times with EtOAc
  3. extractionThe organic layers were extracted with water
  4. dry with materialdried over sodium sulfate
  5. customevaporated to dryness
  6. customThe crude product was purified by flash chromatography on a silica gel column
  7. washeluting with an ethyl acetate

Sources & evidence

ORD record
ord-79fe3216a536445d83918091d347e2d4
Source dataset
uspto-grants-2016_04
Patent number
US09315498B2

Reaction notes

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