N-methyl-2-pyrrolidone → 3-((Trimethylsilyl)ethynyl)pyridin-2-amine

HRID 1927207Notes

Reaction equation

HRID 1927207 reaction equation
CN1C(=O)CCC1.[NH2:8][C:9]1[C:14](Br)=[CH:13][CH:12]=[CH:11][N:10]=1.[CH3:16][Si:17]([C:20]#[CH:21])([CH3:19])[CH3:18].C(N(CC)C(C)C)(C)C>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.[Cu]I.O>[CH3:16][Si:17]([C:20]#[C:21][C:14]1[C:9]([NH2:8])=[N:10][CH:11]=[CH:12][CH:13]=1)([CH3:19])[CH3:18]

Participants

8

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 8177002-Amino-3-bromopyridine

Product 1

HCID 574756663-((Trimethylsilyl)ethynyl)pyridin-2-amineYield 93.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

To a NMP (120 mL) solution of 2-amino-3-bromopyridine (5.72 g, 33.1 mmol) were added trimethylsilylacetylene (9.36 mL, 66.2 mmol), tetrakis(triphenylphosphine)palladium(0) (1.91 g, 1.66 mmol), copper(I) iodide (630 mg, 3.31 mmol), and N,N-diisopropylethylamine (11.5 mL, 66.2 mmol) at room temperature, which was stirred for 6 hours at 70° C. under a nitrogen atmosphere. Water was added at 0° C. to the reaction solution, and then extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine, after which it was dried over anhydrous magnesium sulfate and filtered, and then the filtrate was concentrated under a reduced pressure. The residue was purified by silica gel chromatography (heptane:ethyl acetate=2:1) to obtain the titled compound (5.9 g).

Workup

  1. extractionextraction
  2. washThe organic layer was washed with water and saturated brine
  3. dry with materialafter which it was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under a reduced pressure
  6. customThe residue was purified by silica gel chromatography (heptane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-7d75dc9a37e44be78013664810ad4147
Source dataset
uspto-grants-2012_05
Patent number
US08183264B2

Reaction notes

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