Water → HCID 90052476, compound

HRID 2284778Notes

Reaction equation

HRID 2284778 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:5](I)=[CH:4][N:3]=1.[C:15]([C:17]1[CH:18]=[C:19]([NH:23][C:24](=[O:36])[C@@H:25]([N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH3:26])[CH:20]=[CH:21][CH:22]=1)#[CH:16].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]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:5]([C:16]#[C:15][C:17]2[CH:18]=[C:19]([NH:23][C:24](=[O:36])[C@@H:25]([N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:33])[CH3:32])[CH3:26])[CH:20]=[CH:21][CH:22]=2)=[CH:4][N:3]=1

Participants

9

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 44122610HCID 44122610, compoundHCID 90051758HCID 90051758, compound

Product 1

HCID 90052476HCID 90052476, compoundYield 94.8%

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-(2-chloro-5-iodopyrimidin-4-yl)morpholine (H11, 300 mg), (S)-tert-butyl (1-((3-ethynylphenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (G1, 558 mg), bis(triphenylphosphine)palladium(II) dichloride (32 mg) and copper(I) iodide (9 mg) in N,N-dimethylformamide (5 mL), triethylamine (640 μL) was added at room temperature, and the mixture was stirred at the same temperature for 2 hours. To the reaction mixture, water and ethyl acetate 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 basic silica gel column chromatography (eluent, 85 to 70% hexane in ethyl acetate) to obtain (S)-tert-butyl (1-((3-((2-chloro-4-morpholinopyrimidin-5-yl)ethynyl)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (L5, 437 mg).

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 basic silica gel column chromatography (eluent, 85 to 70% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-6301575b81b949f49b92b2e067b4a9f3
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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