Water → HCID 90051762, compound

HRID 2284733Notes

Reaction equation

HRID 2284733 reaction equation
I[C:2]1[C:3]([NH:17][CH2:18][CH2:19][CH3:20])=[N:4][C:5]([NH:8][C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[CH2:21]([OH:26])[CH2:22][CH2:23][C:24]#[CH:25].C(OCC)(=O)C.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.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:26][CH2:21][CH2:22][CH2:23][C:24]#[C:25][C:2]1[C:3]([NH:17][CH2:18][CH2:19][CH3:20])=[N:4][C:5]([NH:8][C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)=[N:6][CH:7]=1

Participants

10

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 793464-Pentyn-1-olHCID 90051761HCID 90051761, compound

Product 1

HCID 90051762HCID 90051762, compoundYield 76.3%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a suspension of 4-((5-iodo-4-(propylamino)pyrimidin-2-yl)amino)benzonitrile (F25, 289 mg), bis(triphenylphosphine)palladium(II) dichloride (53 mg) and copper(I) iodide (28 mg) in N,N-dimethylformamide (4 mL), triethylamine (322 μL), 4-pentyn-1-ol (304 mg), and tetrakis(triphenylphosphine)palladium(0) (88 mg) were added at room temperature, and the mixture was stirred at the same temperature for 3 hours. To the reaction mixture, ethyl acetate and water were added, and the insoluble matter was removed by filtration through Cerite. The organic layer was separated, washed successively with water, saturated aqueous ammonium chloride 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 (eluent, 90 to 0% hexane in ethyl acetate) to obtain 4-((5-(5-hydroxy-1-pentyn-1-yl)-4-(propylamino)pyrimidin-2-yl)amino)benzonitrile (G11, 195 mg).

Workup

  1. additionwere added at room temperature
  2. customthe insoluble matter was removed by filtration through Cerite
  3. customThe organic layer was separated
  4. washwashed successively with water, saturated aqueous ammonium chloride and 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 0% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-9d9f941a6f734e25aea2cf8ad6a6f527
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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