Triethylamine → HCID 86712625, compound

HRID 1778956Notes

Reaction equation

HRID 1778956 reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC.[C:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH2:35][C:36]([O:38][CH3:39])=[O:37])#[CH:28].[Cl:40][C:41]1[N:46]=[C:45](Cl)[C:44]([CH3:48])=[CH:43][N:42]=1>CN(C=O)C.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:40][C:41]1[N:46]=[C:45]([C:28]#[C:27][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH2:35][C:36]([O:38][CH3:39])=[O:37])[C:44]([CH3:48])=[CH:43][N:42]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 74508Pyrimidine, 2,4-dichloro-5-methyl-HCID 45789861Methyl 2-(2-ethynylphenyl)acetate

Product 1

HCID 86712625HCID 86712625, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

PPh3 (31 mg, 0.12 mmol), PdCl2(PPh3)2 (84 mg, 0.12 mmol), Et3N (0.67 mL, 4.8 mmol) and methyl 2-(2-ethynylphenyl)acetate (K1) (0.25 g, 1.4 mmol) were added to a solution of 2,4-dichloro-5-methylpyrimidine (0.20 g, 1.2 mmol) in anhydrous DMF (5.0 mL). The solution was degassed with nitrogen for 10 minutes before the addition of CuI (23 mg, 0.12 mmol). The resulting mixture was heated under microwave irradiation at 120° C. for 15 minutes then diluted with EtOAc (30 mL) and filtered through Celite. The filtrate was evaporated under reduced pressure and the resulting residue adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-35% EtOAc in petroleum benzine 40-60° C.) to give the title compound K7 as a yellow solid (0.28 g, 78%); 1H NMR (400 MHz, CDCl3) δ 8.49 (s, 1H), 7.66 (d, J=7.7 Hz, 1H), 7.46-7.40 (m, 1H), 7.39-7.31 (m, 2H), 3.93 (s, 2H), 3.71 (s, 3H), 2.45 (s, 3H). LCMS-A: rt 5.993 min; m/z 301 [M+H]+.

Workup

  1. filtrationfiltered through Celite
  2. customThe filtrate was evaporated under reduced pressure
  3. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-35% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-1e44b94527d44e2a810bbf86e9d20850
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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