Water → 2-(5-(4-(Benzyloxy)-2-((3-fluorophenyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione

HRID 2284755Notes

Reaction equation

HRID 2284755 reaction equation
[CH2:1]([O:8][C:9]1[C:14](I)=[CH:13][N:12]=[C:11]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:24]([N:29]1[C:33](=[O:34])[C:32]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:31]2[C:30]1=[O:39])[CH2:25][CH2:26][C:27]#[CH:28].C(OCC)(=O)C.O>CN(C)C=O.C(N(CC)CC)C.[Cu]I.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>[CH2:1]([O:8][C:9]1[C:14]([C:28]#[C:27][CH2:26][CH2:25][CH2:24][N:29]2[C:30](=[O:39])[C:31]3[C:32](=[CH:35][CH:36]=[CH:37][CH:38]=3)[C:33]2=[O:34])=[CH:13][N:12]=[C:11]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 11769822N-(4-Pentynyl)phthalimideHCID 900521484-(benzyloxy)-N-(3-fluorophenyl)-5-iodopyrimidin-2-amine

Product 1

HCID 1178570002-(5-(4-(Benzyloxy)-2-((3-fluorophenyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dioneYield 95.6%

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 solution of 4-(benzyloxy)-N-(3-fluorophenyl)-5-iodopyrimidin-2-amine (J2, 60 mg) and N-(4-pentynyl)phthalimide (76 mg) in N,N-dimethylformamide (500 μL), triethylamine (98 μL), copper(I) iodide (14 mg) and bis(triphenylphosphine)palladium(II) dichloride (10 mg) were added at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture, ethyl acetate and water were added. The organic layer was separated, washed successively with 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 silica gel column chromatography to obtain 2-(5-(4-(benzyloxy)-2-((3-fluorophenyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (J3, 69 mg) as pale green solid.

Workup

  1. customThe organic layer was separated
  2. washwashed successively with water and saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-099c610a71f94fc7b9f471ccfb01743a
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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