Water → 2-(5-(2-Chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione

HRID 2284770Notes

Reaction equation

HRID 2284770 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH3:11])[C:5](I)=[CH:4][N:3]=1.[CH2:13]([N:18]1[C:22](=[O:23])[C:21]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:20]2[C:19]1=[O:28])[CH2:14][CH2:15][C:16]#[CH:17].O.C(OCC)(=O)C>CN(C)C=O.C(N(CC)CC)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:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH3:11])[C:5]([C:17]#[C:16][CH2:15][CH2:14][CH2:13][N:18]2[C:19](=[O:28])[C:20]3[C:21](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]2=[O:23])=[CH:4][N:3]=1

Participants

9

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 11769822N-(4-Pentynyl)phthalimideHCID 900517702-chloro-5-iodo-N-propylpyrimidin-4-amine

Product 1

HCID 900521562-(5-(2-Chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dioneYield 107.2%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-chloro-5-iodo-N-propylpyrimidin-4-amine (F1, 1.45 g), N-(4-pentynyl)phthalimide (2.08 g), bis(triphenylphosphine)palladium(II) dichloride (171 mg) and copper(I) iodide (47 mg) in N,N-dimethylformamide (15 mL), triethylamine (3.4 mL) was added at room temperature, and the mixture was stirred at 60° C. for 1 hour and 15 minutes. The reaction mixture was cooled to room temperature, and then water and ethyl acetate were added to the reaction mixture. The organic layer was separated, washed successively with saturated aqueous sodium hydrogencarbonate, water and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (eluent, 70 to 40% hexane in ethyl acetate) to obtain 2-(5-(2-chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (K1, 2.00 g).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe organic layer was separated
  3. washwashed successively with saturated aqueous sodium hydrogencarbonate, water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (eluent, 70 to 40% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-590d4d1aafe146fab82e79a7c6009be2
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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