Piperidine → 1-Methyl-4-(5-((trimethylsilyl)ethynyl)pyridin-2-yl)piperazine

HRID 2383580Notes

Reaction equation

HRID 2383580 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.N1CCCCC1.[CH3:21][Si:22]([C:25]#[CH:26])([CH3:24])[CH3:23].CCN(CC)CC>CCOCC.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>[CH3:14][N:11]1[CH2:12][CH2:13][N:8]([C:5]2[CH:4]=[CH:3][C:2]([C:26]#[C:25][Si:22]([CH3:24])([CH3:23])[CH3:21])=[CH:7][N:6]=2)[CH2:9][CH2:10]1

Participants

8

Reactant 4

HCID 8082PiperidineHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 164142065-Bromo-2-(4-methylpiperazin-1-yl)pyridine

Product 1

HCID 667304181-Methyl-4-(5-((trimethylsilyl)ethynyl)pyridin-2-yl)piperazineYield 61%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1-(5-bromopyridin-2-yl)-4-methylpiperazine (501.7 mg, 1.96 mmol), PdCl2(PPh3)2 (51.1 mg, 0.073 mmol) and copper(I) iodide (39.9 mg, 0.21 mmol) was flushed with argon for 10 min prior to addition of piperidine (1.25 mL, 12.7 mmol) and trimethylsilylacetylene (1.40 mL, 9.9 mmol). The resulting mixture was heated at 90° C. in a sealed vial for 3 d. The reaction mixture was cooled to room temperature and the volatiles were removed in vacuo. Chromatography on Biotage (silica, SNAP-25 g, 5-15% MeOH in DCM) yielded an impure product. A second chromatography on Biotage (silica, SNAP-25 g, 0-3% Et3N in Et2O) gave 1-methyl-4-(5-((trimethylsilyl)ethynyl)pyridin-2-yl)piperazine (325.7 mg, 61%). 1H NMR (400 MHz, CDCl3) δ ppm 8.29 (d, J=1.3 Hz, 1H), 7.53 (dd, J=8.9, 2.4 Hz, 1H), 6.55 (d, J=8.8 Hz, 1H), 3.67-3.52 (m, 4H), 2.57-2.44 (m, 4H), 2.35 (s, 3H); MS ESI [M+H]+ 274.0, calcd for [C15H23N3Si+H]+ 274.2.

Workup

  1. customwas flushed with argon for 10 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customthe volatiles were removed in vacuo
  4. customChromatography on Biotage (silica, SNAP-25 g, 5-15% MeOH in DCM) yielded an impure product

Sources & evidence

ORD record
ord-4e2ad0ac293642deb1fa17d18890ba47
Source dataset
uspto-grants-2012_09
Patent number
US08263596B2

Reaction notes

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