Trimethylsilylacetylene → HCID 67228299, compound

HRID 1515577Notes

Reaction equation

HRID 1515577 reaction equation
[CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].[CH3:7][O:8][C:9](=[O:18])[C:10]1[CH:15]=[C:14](I)[C:13]([NH2:17])=[N:12][CH:11]=1.C(N(C(C)C)CC)(C)C>CN(C)C=O.[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>[CH3:7][O:8][C:9](=[O:18])[C:10]1[CH:15]=[C:14]([C:6]#[C:5][Si:2]([CH3:4])([CH3:3])[CH3:1])[C:13]([NH2:17])=[N:12][CH:11]=1

Participants

7

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 15350913Methyl 6-amino-5-iodopyridine-3-carboxylate

Product 1

HCID 67228299HCID 67228299, compoundYield 72.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

Trimethylsilyl acetylene (10.5 mL, 79.1 mmol) was added to a solution of 6-amino-5-iodo-nicotinic acid methyl ester (11 g, 39.6 mmol), copper (I) iodide (754 mg, 4.0 mmol), tetrakis(triphenylphosphine)palladium(0) (2.3 g, 2.0 mmol) and diisopropylethylamine (21 mL, 118.7 mmol) in N,N-dimethyl formamide (80 mL) at 0° C. After addition, the reaction mixture was allowed to warm up to 25° C. and stirred for 2 h. The mixture was extracted with ethyl acetate, washed with brine and dried over sodium sulfate. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (QingDao silica gel, 200-300 mesh, 5% dichloromethane/hexanes to 60% dichloromethane/hexanes) to afford 6-amino-5-trimethylsilanylethynyl-nicotinic acid methyl ester (7.1 g, 72%) as a light yellow solid: 1H NMR (400 MHz, CDCl3) δ ppm 0.28 (s, 9H), 3.88 (s, 3H), 5.58 (br. s., 2H), 8.14 (d, J=2.2 Hz, 1H), 8.66 (d, J=2.2 Hz, 1H).

Workup

  1. additionAfter addition
  2. extractionThe mixture was extracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was evaporated in vacuo
  6. customthe residue was purified by flash column chromatography (QingDao silica gel, 200-300 mesh, 5% dichloromethane/hexanes to 60% dichloromethane/hexanes)

Sources & evidence

ORD record
ord-4d5b80517c3349688324e2c8d6dad401
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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