Triethylamine → 1-(4-methoxy-benzyl)-5-pyrrolidin-1-yl-3-trimethylsilanylethynyl-1H-[1,2,4]triazole

HRID 1054946Notes

Reaction equation

HRID 1054946 reaction equation
Br[C:2]1[N:6]=[C:5]([N:7]2[CH2:11][CH2:10][CH2:9][CH2:8]2)[N:4]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[N:3]=1.[C:21]([Si:23]([CH3:26])([CH3:25])[CH3:24])#[CH:22].C(N(CC)CC)C>O1CCCC1.[Cu]I.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][N:4]2[C:5]([N:7]3[CH2:11][CH2:10][CH2:9][CH2:8]3)=[N:6][C:2]([C:22]#[C:21][Si:23]([CH3:26])([CH3:25])[CH3:24])=[N:3]2)=[CH:14][CH:15]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 900169503-bromo-1-(4-methoxy-benzyl)-5-pyrrolidin-1-yl-1H-[1,2,4]triazole

Product 1

HCID 900165621-(4-methoxy-benzyl)-5-pyrrolidin-1-yl-3-trimethylsilanylethynyl-1H-[1,2,4]triazoleYield 45.9%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 3-bromo-1-(4-methoxybenzyl)-5-(pyrrolidin-1-yl)-1H-1,2,4-triazole (197 mg, 584 μmol, Eq: 1.00), ethynyltrimethylsilane (115 mg, 164 μl, 1.17 mmol, Eq: 2) and triethylamine (88.7 mg, 122 μl, 876 μmol, Eq: 1.5) in tetrahydrofuran (3 ml) was purged for 5 minutes with nitrogen. Then copper (I) iodide (1.11 mg, 5.84 μmol, Eq: 0.01), bis(triphenylphosphine) palladium(II) chloride (4.1 mg, 5.84 μmol, Eq: 0.01) and triphenylphosphine (1.53 mg, 5.84 μmol, Eq: 0.01) were added, the vessel was capped and heated to 75° C. for 18 hours. The crude material was applied on silicagel and purified by flash chromatography over a 20 g silicagel column using heptane/ethyl acetate 10-30% as eluent affording 1-(4-methoxy-benzyl)-5-pyrrolidin-1-yl-3-trimethylsilanylethynyl-1H-[1,2,4]triazole (95 mg/45.9%) as an orange oil. MS: m/e=355.4 (M+H+)

Workup

  1. customwas purged for 5 minutes with nitrogen
  2. customthe vessel was capped
  3. custompurified by flash chromatography over a 20 g silicagel column

Sources & evidence

ORD record
ord-140f27199723490e9e77c6eee6537d5f
Source dataset
uspto-grants-2016_07
Patent number
US09394311B2

Reaction notes

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