Triethylamine → 2-((1-ethyl-5-(pyrrolidin-1-yl)-1H-1,2,4-triazol-3-yl)ethynyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine

HRID 1054982Notes

Reaction equation

HRID 1054982 reaction equation
[CH2:1]([N:3]1[C:7]([N:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)=[N:6][C:5]([C:13]#[CH:14])=[N:4]1)[CH3:2].Br[C:16]1[N:26]=[C:19]2[C:20]([CH3:25])=[N:21][CH:22]=[C:23]([CH3:24])[N:18]2[N:17]=1.C(N(CC)CC)C>O1CCOCC1.[Cu]I.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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([N:3]1[C:7]([N:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)=[N:6][C:5]([C:13]#[C:14][C:16]2[N:26]=[C:19]3[C:20]([CH3:25])=[N:21][CH:22]=[C:23]([CH3:24])[N:18]3[N:17]=2)=[N:4]1)[CH3:2]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 900168721-ethyl-3-ethynyl-5-pyrrolidin-1-yl-1H-[1,2,4]triazoleHCID 900257482-Bromo-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine

Product 1

HCID 727050902-((1-ethyl-5-(pyrrolidin-1-yl)-1H-1,2,4-triazol-3-yl)ethynyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazineYield 37.2%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 1-ethyl-3-ethynyl-5-(pyrrolidin-1-yl)-1H-1,2,4-triazole (79 mg, 415 μmol, Eq: 1.00), 2-bromo-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine (104 mg, 457 μmol, Eq: 1.1) and triethylamine (63.0 mg, 86.8 μl, 623 μmol, Eq: 1.5) in dioxane (2.11 ml) was purged with argon, then copper (I) iodide (1.58 mg, 8.31 μmol, Eq: 0.02), bis(triphenylphosphine)palladium(II) chloride (5.83 mg, 8.31 μmol, Eq: 0.02) and triphenylphosphine (2.18 mg, 8.31 μmol, Eq: 0.02) were added, the vessel was capped and heated for 18 hours to 110° C. The crude material was applied on silica gel and purified by flash chromatography over a 20 g silica gel column using ethyl acetate 100% as eluent affording 2-((1-ethyl-5-(pyrrolidin-1-yl)-1H-1,2,4-triazol-3-yl)ethynyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine (52 mg, 37.2%) as an orange oil. MS: m/z=337.4 (M+H+)

Workup

  1. customwas purged with argon
  2. customthe vessel was capped
  3. temperatureheated for 18 hours to 110° C
  4. custompurified by flash chromatography over a 20 g silica gel column

Sources & evidence

ORD record
ord-8cc4632c9cbc4ad994686a2d96f0394a
Source dataset
uspto-grants-2016_07
Patent number
US09394311B2

Reaction notes

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