Triethylamine → [2-Chloro-5-(3,3-diethoxy-prop-1-ynyl)-pyrimidin-4-yl]-(1-ethyl-propyl)-amine

HRID 2189283Notes

Reaction equation

HRID 2189283 reaction equation
Br[C:2]1[C:3]([NH:9][CH:10]([CH2:13][CH3:14])[CH2:11][CH3:12])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH2:15]([O:17][CH:18]([O:21][CH2:22][CH3:23])[C:19]#[CH:20])[CH3:16].CCN(CC)CC>CN(C=O)C.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:8][C:5]1[N:4]=[C:3]([NH:9][CH:10]([CH2:13][CH3:14])[CH2:11][CH3:12])[C:2]([C:20]#[C:19][CH:18]([O:21][CH2:22][CH3:23])[O:17][CH2:15][CH3:16])=[CH:7][N:6]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 662853,3-DiethoxypropyneHCID 580158915-bromo-2-chloro-N-(pentan-3-yl)pyrimidin-4-amine

Product 1

HCID 58015829[2-Chloro-5-(3,3-diethoxy-prop-1-ynyl)-pyrimidin-4-yl]-(1-ethyl-propyl)-amineYield 37.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

To a mixture of (5-Bromo-2-chloro-pyrimidin-4-yl)-(1-ethyl-propyl)-amine (420 mg, 1.5 mmol) and propiolaldehyde diethyl acetal (0.32 mL, 2.25 mmol) in DMF (6 mL) is added PdCl2(PPh3)2 (105 mg, 0.15 mmol) and CuI (28 mg, 0.15 mmol), followed by Et3N (0.42 mL, 3 mmol). The mixture is degassed and heated at 55° C. for 16 h. Then the mixture is cooled down to room temperature, diluted with EtOAc, washed with water and brine. The organic layer is dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product is purified by column chromatography (SiO2, EtOAc:Heptane=5:95 to 40:60) to give 182 mg of the title compound as a light brown oil.

Workup

  1. customThe mixture is degassed
  2. temperatureThen the mixture is cooled down to room temperature
  3. additiondiluted with EtOAc
  4. washwashed with water and brine
  5. dry with materialThe organic layer is dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product is purified by column chromatography (SiO2, EtOAc:Heptane=5:95 to 40:60)

Sources & evidence

ORD record
ord-fa114cb528b84c98bb42002586611d0e
Source dataset
uspto-grants-2012_12
Patent number
US08324225B2

Reaction notes

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