Triethylamine → 2-Chloro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyrimidine

HRID 1913907Notes

Reaction equation

HRID 1913907 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.[CH3:9][C:10]1[S:11][CH:12]=[C:13]([C:15]#[CH:16])[N:14]=1.C(N(CC)CC)C>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.[Cu]I>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:16]#[C:15][C:13]2[N:14]=[C:10]([CH3:9])[S:11][CH:12]=2)=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 6066655-Bromo-2-chloropyrimidineHCID 116223344-Ethynyl-2-methylthiazole

Product 1

HCID 578230292-Chloro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyrimidine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
60 °C

Procedure

2-Chloro-5-bromopyrimidine (5.0 g, 26 mmol), 2-methyl-4-ethynyl-1,3-thiazole (3.2 g, 26 mmol), tetrakis(triphenylphosphine)palladium(0) (0.6 g, 0.5 mmol), copper(I) iodide (0.1 g, 0.5 mmol) and triethylamine (13 g, 130 mmol) were added to deoxygenated toluene (50 mL) at room temperature. The reaction was then warmed to 60° C. Stirring continued for 2.5 hrs and the reaction contents were then poured in to a separatory funnel and partitioned with EtOAc (100 mL) and water (100 mL). The organic layer was then washed with water twice (250 mL each). The organic layer were dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was chromatographed on SiO2, eluting with 1:1 EtOAc:hexanes to afford 2-chloro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyrimidine as a tan solid. 1H-NMR (CDCl3, 300 MHz) δ 8.78 (s, 2H), 7.52 (s, 1H), 2.78 (s, 3H).

Workup

  1. customto deoxygenated toluene (50 mL) at room temperature
  2. customthe reaction contents
  3. additionwere then poured in to a separatory funnel
  4. custompartitioned with EtOAc (100 mL) and water (100 mL)
  5. washThe organic layer was then washed with water twice (250 mL each)
  6. dry with materialThe organic layer were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was chromatographed on SiO2
  10. washeluting with 1:1 EtOAc

Sources & evidence

ORD record
ord-7ce55ea1985e4b3ea87fe218fe521335
Source dataset
uspto-grants-2013_12
Patent number
US08609852B2

Reaction notes

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