Triethylamine → 5-chloro-1-(4-methoxybenzyl)-3-(5-methyl-3-((trimethylsilyl)ethynyl)pyridin-2-ylamino)pyrazin-2(1H)-one

HRID 1882208Notes

Reaction equation

HRID 1882208 reaction equation
Br[C:2]1[C:3]([NH:9][C:10]2[C:11](=[O:26])[N:12]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[CH:13]=[C:14]([Cl:16])[N:15]=2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.C(N(CC)CC)C.[CH3:34][Si:35]([C:38]#[CH:39])([CH3:37])[CH3:36]>C1COCC1.[Cu](I)I.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:16][C:14]1[N:15]=[C:10]([NH:9][C:3]2[C:2]([C:39]#[C:38][Si:35]([CH3:37])([CH3:36])[CH3:34])=[CH:7][C:6]([CH3:8])=[CH:5][N:4]=2)[C:11](=[O:26])[N:12]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[CH:13]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 588801533-(3-bromo-5-methylpyridin-2-ylamino)-5-chloro-1-(4-methoxybenzyl)pyrazin-2(1H)-one

Product 1

HCID 588800755-chloro-1-(4-methoxybenzyl)-3-(5-methyl-3-((trimethylsilyl)ethynyl)pyridin-2-ylamino)pyrazin-2(1H)-oneYield 81%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

In a 1 L round bottom combined 3-(3-bromo-5-methylpyridin-2-ylamino)-5-chloro-1-(4-methoxybenzyl)pyrazin-2(1H)-one (51.90 g, 119.12 mmol), triphenylphosphine (1.56 g, 5.96 mmol), (Ph3P)PdCl2 (4.18 g, 5.96 mmol) and suspended in anhydrous THF (450 mL). Triethylamine (18.08 g, 178.68 mmol) and trimethylsilyl acetylene (35.10 g, 357.36 mmol) were added next and mixture was stirred at ambient temperature, under N2 for 10 minutes. Copper iodide (catalytic) was added last and reaction was stirred at ambient temperature. Reaction was monitored by analytical LCMS at one hour intervals and CuI was added until reaction is complete. The completed reaction was concentrated in vacuo, taken up with ethyl acetate (700 mL) and brine (300 mL) and filtered off undissolved solids before taking on to extraction. The organic layer was washed with additional brine (4×300 mL), dried with MgSO4, filtered and concentrated in vacuo. Chromatography on silica gel plug with ethyl acetate/hexanes (1/9), two attempts, afforded the desired product (43.36 g. 81% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.11 (s, 9H) 2.26 (s, 3H) 3.73 (s, 3H) 5.00 (s, 2H) 6.91 (d, J=8.59 Hz, 2H) 7.38 (d, J=8.59 Hz, 2H) 7.45 (s, 1H) 7.74 (d, J=2.27 Hz, 1H) 8.25 (d, J=2.27 Hz, 1H) 9.51 (s, 1H). ESI-MS: m/z 453.3 (M+H)+.

Workup

  1. customreaction
  2. stirringwas stirred at ambient temperature
  3. customReaction
  4. waitwas monitored by analytical LCMS at one hour
  5. customThe completed reaction
  6. concentrationwas concentrated in vacuo
  7. filtrationfiltered off undissolved solids
  8. extractionbefore taking on to extraction
  9. washThe organic layer was washed with additional brine (4×300 mL)
  10. dry with materialdried with MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2a427f34f36d4229b4c0963104e9c509
Source dataset
uspto-grants-2012_11
Patent number
US08318939B2

Reaction notes

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