Trimethylsilylacetylene → 2-Amino-3-cyano-4-methyl-5-(trimethylsilylethynyl)pyridine

HRID 1734185Notes

Reaction equation

HRID 1734185 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH3:10])[C:5](I)=[CH:4][N:3]=1.[CH3:12][Si:13]([C:16]#[CH:17])([CH3:15])[CH3:14]>C(#N)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>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH3:10])[C:5]([C:17]#[C:16][Si:13]([CH3:15])([CH3:14])[CH3:12])=[CH:4][N:3]=1

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 113912652-Amino-5-iodo-4-methylnicotinonitrile

Product 1

HCID 197071982-Amino-3-cyano-4-methyl-5-(trimethylsilylethynyl)pyridine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

In another variation in the method to the 2,4-diamino-5,6-disubstituted-5-deazapteridines described above, 2-amino-3-cyano-5-iodo-4-methylpyridine is reacted with trimethylsilylacetylene in the presence of copper(I) iodide and bis(triphenylphosphine)palladium(II) chloride under basic conditions in acetonitrile, affording 2-amino-3-cyano-4-methyl-5-(trimethylsilylethynyl)pyridine. The 5-(trimethylsilylethynyl)pyridine is in turn treated with potassium carbonate in methanol, yielding the corresponding 2-amino-3-cyano-4-methyl-5-ethynylpyridine. The 5-ethynylpyridine is then reacted with an appropriately substituted halide, for example, 4-trifluoromethyl-phenyl iodide, again in the presence of copper(I)iodide and bis(triphenylphosphine)palladium(II) chloride under basic conditions in acetonitrile, yielding a 2-amino-3-cyano-4-methyl-5-(substituted-ethynyl)pyridine, for example, 2-amino-3-cyano-4-methyl-5-[(4-trifluoromethylphenyl)ethynyl]-pyridine. The so-prepared pyridine is then cyclized and hydrohalogenated with chloroformamidine hydrochloride in diglyme, affording the corresponding 2,4-diamino-5-methyl-6-[1-chloro-2-substituted-ethenyl]-5-deazapteridine, for example, 2,4-diamino-5-methyl-6-[1-chloro-2-(4-trifluoromethylphenyl)ethenyl]-5-deazapteridine. Cyclizations with an appropriately substituted 2-amino-3-cyanopyridine and chloroformamidine hydrochloride in diglyme are taught by N. V. Harris et al (J. Med. Chem. 1990, 33, 434-444). Example 10 provides a detailed description of how this reaction is conducted.

Sources & evidence

ORD record
ord-b1fac2e072fb4efcb1afe03f711f5384
Source dataset
uspto-grants-1996_07
Patent number
US05532370

Reaction notes

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