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

HRID 2284749Notes

Reaction equation

HRID 2284749 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)[C:5](I)=[CH:4][N:3]=1.[CH2:14]([N:19]1[C:23](=[O:24])[C:22]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:21]2[C:20]1=[O:29])[CH2:15][CH2:16][C:17]#[CH:18].O>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]([N:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)[C:5]([C:18]#[C:17][CH2:16][CH2:15][CH2:14][N:19]2[C:20](=[O:29])[C:21]3[C:22](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]2=[O:24])=[CH:4][N:3]=1

Participants

8

Reactant 3

HCID 962WaterHCID 11769822N-(4-Pentynyl)phthalimideHCID 900517752-Chloro-5-iodo-4-(pyrrolidin-1-yl)pyrimidine

Product 1

HCID 900517842-(5-(2-Chloro-4-(pyrrolidin-1-yl)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dioneYield 63.9%

Reagents, catalysts & solvents 4

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

Procedure

To a suspension of bis(triphenylphosphine)palladium(II) dichloride (1.02 g) and copper(I) iodide (558 mg) in N,N-dimethylformamide (90 mL), triethylamine (10.2 mL), 2-chloro-5-iodo-4-(pyrrolidin-1-yl)pyrimidine (H1, 4.49 g), and N-(4-pentynyl)phthalimide (4.65 g) were added at room temperature under a nitrogen atmosphere, and the mixture was stirred at the same temperature for 4 hours. To the reaction mixture, water was added. The solid matter was taken by filtration, washed with water, then dried under reduced pressure, and purified by silica gel column chromatography. The obtained solid matter was washed with ethyl acetate, and then dried under reduced pressure to obtain 2-(5-(2-chloro-4-(pyrrolidin-1-yl)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (H2, 3.66 g).

Workup

  1. additionwere added at room temperature under a nitrogen atmosphere
  2. filtrationThe solid matter was taken by filtration
  3. washwashed with water
  4. customdried under reduced pressure
  5. custompurified by silica gel column chromatography
  6. washThe obtained solid matter was washed with ethyl acetate
  7. customdried under reduced pressure

Sources & evidence

ORD record
ord-f585d670720b4b03922a3bd450b8ad71
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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