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

HRID 640077Notes

Reaction equation

HRID 640077 reaction equation
I[C:2]1[C:3]([NH2:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:9][Si:10]([C:13]#[CH:14])([CH3:12])[CH3:11].C(N(CC)C(C)C)(C)C.CN1CCCC1=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.O>[CH3:9][Si:10]([C:13]#[C:14][C:2]1[C:3]([NH2:8])=[N:4][CH:5]=[CH:6][CH:7]=1)([CH3:12])[CH3:11]

Participants

8

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 27631512-Amino-3-iodopyridine

Product 1

HCID 574756663-((Trimethylsilyl)ethynyl)pyridin-2-amineYield 80.7%

Reagents, catalysts & solvents 3

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

Procedure

To a mixture of 3-iodopyridin-2-ylamine (40.2 g, 183 mmol) described in Manufacturing Example 1-2-1, trimethylsilylacetylene (51.7 mL, 366 mmol), copper (I) iodide (3.49 g, 18.3 mmol), N,N-diisopropylethylamine (63.7 mL, 366 mmol) and N-methylpyrrolidinone (200 mL) was added tetrakis(triphenylphosphine)palladium (0) (10.6 g, 9.15 mmol) under nitrogen atmosphere, which was stirred for 3 hours and 10 minutes at room temperature. Water was added to the reaction solution, which was then extracted with ethyl acetate 4 times. The solvent was concentrated under a reduced pressure. The residue was purified by NH silica gel chromatography (heptane:ethyl acetate=4:1). The resulting solution was concentrated under a reduced pressure, and the residue was purified by silica gel chromatography (heptane:ethyl acetate=2:1 then 1:1) to obtain the title compound (28.1 g, 80.7%).

Workup

  1. extractionwas then extracted with ethyl acetate 4 times
  2. concentrationThe solvent was concentrated under a reduced pressure
  3. customThe residue was purified by NH silica gel chromatography (heptane:ethyl acetate=4:1)
  4. concentrationThe resulting solution was concentrated under a reduced pressure
  5. customthe residue was purified by silica gel chromatography (heptane

Sources & evidence

ORD record
ord-8064194eb9d84f189f221d9d05b499e0
Source dataset
uspto-grants-2010_04
Patent number
US07691882B2

Reaction notes

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