5-Bromopyrimidine → HCID 69589426, compound

HRID 2181154Notes

Reaction equation

HRID 2181154 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]#[CH:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:16]1[CH:17]=[N:18][CH:19]=[N:20][CH:21]=1>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([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Cu]I>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]#[C:14][C:16]1[CH:17]=[N:18][CH:19]=[N:20][CH:21]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 783445-BromopyrimidineHCID 11030701(S)-N-Boc-2-ethynylpyrrolidine

Product 1

HCID 69589426HCID 69589426, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

Triethylamine (10 mL) was degassed by bubbling argon over a period of 30 min. (S)-N-tert-Butoxycarbonyl-2-ethynylpyrrolidine (0.300 g, 5.12 mmol), tetrakis(triphenylphosphine)palladium (0.180 g, 0.1 mmol), palladium(II) acetate (0.0346 g, 0.10 mmol), copper (I) iodide (6.25 mg, 0.033 mmol) and 5-bromo-pyrimidine (0.4867 g, 3.07 mmol) were added. The mixture was heated at 110° C. for 9 h, then cooled to room temperature and concentrated by rotary evaporation. The residue was dissolved in chloroform (50 mL) and the organic phase washed with water (25 mL), saturated aqueous NaHCO3 solution (3×20 mL) and water (25 mL), then dried (MgSO4), filtered and concentrated by rotary evaporation. The crude product was purified by column chromatography, eluting with ethyl acetate/hexane (1/1, v/v). Selected fractions containing the product were concentrated via rotary evaporation to give 0.310 g (74%) of a yellow oil.

Workup

  1. customTriethylamine (10 mL) was degassed
  2. additionwere added
  3. temperaturecooled to room temperature
  4. concentrationconcentrated by rotary evaporation
  5. dissolutionThe residue was dissolved in chloroform (50 mL)
  6. washthe organic phase washed with water (25 mL), saturated aqueous NaHCO3 solution (3×20 mL) and water (25 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporation
  10. customThe crude product was purified by column chromatography
  11. washeluting with ethyl acetate/hexane (1/1
  12. additionSelected fractions containing the product
  13. concentrationwere concentrated via rotary evaporation

Sources & evidence

ORD record
ord-231e67aad3ac426281ed990026a4f6cf
Source dataset
uspto-grants-2005_05
Patent number
US06890935B2

Reaction notes

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