Triethylamine → 4-[6-Chloro-4-(4-methoxy-benzyl)-3-oxo-3,4-dihydro-pyrazin-2-ylethynyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1184688Notes

Reaction equation

HRID 1184688 reaction equation
Cl[C:2]1[C:3](=[O:18])[N:4]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[CH:5]=[C:6]([Cl:8])[N:7]=1.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([C:32]#[CH:33])[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C(N(CC)CC)C>CN(C)C=O>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH:29]([C:32]#[C:33][C:2]2[C:3](=[O:18])[N:4]([CH2:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=3)[CH:5]=[C:6]([Cl:8])[N:7]=2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 154984631-(4-methoxybenzyl)-3,5-dichloropyrazine-2(1H)-oneHCID 15550481tert-Butyl 4-ethynylpiperidine-1-carboxylate

Product 1

HCID 679732584-[6-Chloro-4-(4-methoxy-benzyl)-3-oxo-3,4-dihydro-pyrazin-2-ylethynyl]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3,5-dichloro-1-(4-methoxy-benzyl)-1H-pyrazin-2-one (285 mg; for preparation see Tetrahedron Letters 2010, 51, 1739) and 4-ethynyl-piperidine-1-carboxylic acid tert-butyl ester (272 mg), triethylamine (2 mL) and N,N-dimethylformamide (2 mL) in a microwave oven suited vessel charged with a stir bar is sparged with argon for 10 min. Copper (I) iodide (8 mg) and Pd(PPh3)2Cl2 (10 mg) are added and the vessel is capped. The resulting mixture is stirred under microwave irradiation at 80° C. for 15 min. After cooling the mixture to room temperature, ethyl acetate is added. The organic phase is washed with 2 N aqueous citric acid, water, and brine, dried (MgSO4) and the solvent is evaporated. The residue is chromatographed on silica gel (ethyl acetate/cyclohexane 40:60) to give the title compound. Yield: 440 mg (96% of theory); LC (method 2): tR=1.47 min; Mass spectrum (ESI+): m/z=458 [M+H]+.

Workup

  1. additioncharged with a stir bar
  2. customis sparged with argon for 10 min
  3. additionCopper (I) iodide (8 mg) and Pd(PPh3)2Cl2 (10 mg) are added
  4. customthe vessel is capped
  5. temperatureAfter cooling the mixture to room temperature
  6. additionethyl acetate is added
  7. washThe organic phase is washed with 2 N aqueous citric acid, water, and brine
  8. dry with materialdried (MgSO4)
  9. customthe solvent is evaporated
  10. customThe residue is chromatographed on silica gel (ethyl acetate/cyclohexane 40:60)

Sources & evidence

ORD record
ord-e56c0a0090404f2491dd9347d6d4404b
Source dataset
uspto-grants-2014_03
Patent number
US08669271B2

Reaction notes

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