1-(But-3-yn-1-yl)piperidine → 2-(4-Piperidin-1-yl-but-1-ynyl)-5-piperidin-1-ylmethyl-pyridine

HRID 30463Notes

Reaction equation

HRID 30463 reaction equation
[N:1]1([CH2:7][C:8]2[CH:9]=[CH:10][C:11](OS(C(F)(F)F)(=O)=O)=[N:12][CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:22]([N:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[CH2:23][C:24]#[CH:25]>CN(C=O)C.C(Cl)Cl.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>[NH3:1].[N:26]1([CH2:22][CH2:23][C:24]#[C:25][C:11]2[CH:10]=[CH:9][C:8]([CH2:7][N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:13][N:12]=2)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

8

Reactant 2

HCID 131559861-(But-3-yn-1-yl)piperidineHCID 86074933Trifluoro-methanesulfonic acid 5-piperidin-1-ylmethyl-pyridin-2-yl ester

Product 2

HCID 222AmmoniaYield 3%HCID 115731942-(4-Piperidin-1-yl-but-1-ynyl)-5-piperidin-1-ylmethyl-pyridineYield 20.7%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of trifluoro-methanesulfonic acid 5-piperidin-1-ylmethyl-pyridin-2-yl ester (0.10 g, 0.31 mmol), 1-but-3-ynyl-piperidine (0.051 g, 0.37 mmol), and TEA (2 mL) in dry DMF (1 mL) was added dichlorobis(triphenylphosphine)-palladium(II) (0.004 g, 0.006 mmol) and copper(I) iodide (0.004 g, 0.016 mmol). The reaction mixture was heated at 80° C. for 4 h, cooled to rt, diluted with DCM (25 mL), and filtered through a pad of diatomaceous earth. The mixture was diluted with 1 N NaOH (25 mL) and extracted with DCM (3×25 mL). The organic layers were combined, dried (Na2SO4), and concentrated, and chromatography of the resulting residue (SiO2: 3-6% 2 M NH3 in MeOH/DCM) gave the title compound (0.01 g, 10%). MS (ESI): exact mass calcd. for C20H29N3, 311.2; m/z found, 312.5 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.45 (d, J=2.0, 1H), 7.62 (d, J =8.3, 1H), 7.25 (d, J=8.1, 1H), 3.47 (s, 2H), 2.74-2.70 (m, 4H), 2.62-2.59 (m, 4H), 2.37 (br s, 4H), 1.65-1.55 (m, 8H), 1.46-1.44 (m, 4H).

Workup

  1. temperaturecooled to rt
  2. filtrationfiltered through a pad of diatomaceous earth
  3. additionThe mixture was diluted with 1 N NaOH (25 mL)
  4. extractionextracted with DCM (3×25 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-09776d8ce47a4d5890b9f219d4cd8634
Source dataset
uspto-grants-2008_09
Patent number
US07423147B2

Reaction notes

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