Triethylamine → HCID 90051808, compound

HRID 2284815Notes

Reaction equation

HRID 2284815 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH3:11])[C:5](I)=[C:4]([CH3:13])[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].C(N(CC)CC)C.[Cl-].[NH4+]>CN(C)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.C(OCC)(=O)C>[Cl:1][C:2]1[N:3]=[C:4]([CH3:13])[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])=[C:6]([NH:8][CH2:9][CH2:10][CH3:11])[N:7]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 11769822N-(4-Pentynyl)phthalimideHCID 90051810HCID 90051810, compound

Product 1

HCID 90051808HCID 90051808, compoundYield 68.6%

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
45 °C

Procedure

To a solution of 2-chloro-5-iodo-6-methyl-N-propylpyrimidin-4-amine (T2, 150 mg) in N,N-dimethylformamide (3 mL), N-(4-pentynyl)phthalimide (133 mg), bis(triphenylphosphine)palladium(II) dichloride (34 mg), copper(I) iodide (18 mg) and triethylamine (334 μL) were added at room temperature, and the mixture was stirred at 45° C. for 1 hour under a nitrogen atmosphere. The reaction mixture was cooled to room temperature, and then saturated aqueous ammonium chloride and ethyl acetate were added to the reaction mixture. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, washed with 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 (eluent, 90 to 70% hexane in ethyl acetate) to obtain 2-(5-(2-chloro-4-methyl-6-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (T3, 131 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washwashed with saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (eluent, 90 to 70% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-2437c5d3eec644fdbf80e2fb4b3ca1dd
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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