Acetonitrile → 6-[(3-aminophenyl)ethynyl]-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine

HRID 1925948Notes

Reaction equation

HRID 1925948 reaction equation
I.I[C:3]1[N:8]=[CH:7][N:6]=[C:5]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:18]=[N:19][C:20]([CH3:23])=[CH:21][CH:22]=3)=[C:12]([CH3:24])[CH:11]=2)[C:4]=1[NH2:25].[C:26](#[N:28])[CH3:27]>C(N(CC)CC)C.C(C1C=C(C=CC=1)N)#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>[NH2:28][C:26]1[CH:24]=[C:12]([C:13]#[C:14][C:3]2[N:8]=[CH:7][N:6]=[C:5]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]4[CH:18]=[N:19][C:20]([CH3:23])=[CH:21][CH:22]=4)=[C:12]([CH3:24])[CH:11]=3)[C:4]=2[NH2:25])[CH:11]=[CH:10][CH:27]=1

Participants

7

Reactant 2

HCID 6342AcetonitrileHCID 866157476-iodo-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine hydroiodide

Product 1

HCID 675214096-[(3-aminophenyl)ethynyl]-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolventHCID 104682Benzenamine, 3-ethynyl-Solvent

Procedure

6-Iodo-N4-{3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}pyrimidine-4,5-diamine hydriodide (200 mg) was dissolved in a mixed solvent of acetonitrile (7.6 mL)/triethylamine (5.72 mL), 3-ethynylaniline (0.0574 mL), trans-dichlorobis(triphenylphosphine)palladium(II) (15.4 mg) and copper(I) iodide (5.3 mg) were sequentially added, and the mixture was stirred under a nitrogen stream at room temperature for 1.5 hrs. The reaction mixture was concentrated under reduced pressure and the residue was separated and purified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→ethyl acetate:methanol=80:20) to give the title compound (157 mg).

Workup

  1. additionwere sequentially added
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe residue was separated
  4. custompurified by silica gel column chromatography (eluent, hexane:ethyl acetate=80:20→ethyl acetate:methanol=80:20)

Sources & evidence

ORD record
ord-57b1e52f39764c569ad5330fb612658b
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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