Triethylamine → 1-ethyl-5-pyrrolidin-1-yl-3-trimethylsilanylethynyl-1H-[1,2,4]triazole

HRID 1054977Notes

Reaction equation

HRID 1054977 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][CH3:13])[N:3]=1.[C:14]([Si:16]([CH3:19])([CH3:18])[CH3:17])#[CH:15].C(N(CC)CC)C>O1CCCC1.[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>[CH2:12]([N:4]1[C:5]([N:7]2[CH2:11][CH2:10][CH2:9][CH2:8]2)=[N:6][C:2]([C:15]#[C:14][Si:16]([CH3:19])([CH3:18])[CH3:17])=[N:3]1)[CH3:13]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 66111Trimethylsilylacetylene2×HCID 900181923-bromo-1-ethyl-5-(pyrrolidin-1-yl)-1H-1,2,4-triazole

Product 1

HCID 900256441-ethyl-5-pyrrolidin-1-yl-3-trimethylsilanylethynyl-1H-[1,2,4]triazoleYield 47.5%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalyst2×HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418476HCID 178418476, compoundCatalyst2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-bromo-1-ethyl-5-(pyrrolidin-1-yl)-1H-1,2,4-triazole (240 mg, 979 μmol, Eq: 1.00), ethynyltrimethylsilane (192 mg, 275 μl, 1.96 mmol, Eq: 2) and triethylamine (149 mg, 205 μl, 1.47 mmol, Eq: 1.5) in tetrahydrofuran (3.65 ml) was purged for 5 minutes with nitrogen. Then copper (I) iodide (1.86 mg, 9.79 μmol, Eq: 0.01), bis(triphenylphosphine)palladium(II) chloride (6.87 mg, 9.79 μmol, Eq: 0.01) and triphenylphosphine (2.57 mg, 9.79 μmol, Eq: 0.01) were added, the vessel was capped and heated to 120° C. for 1 day. Once more copper (I) iodide (1.86 mg, 9.79 μmol, Eq: 0.01), triphenylphosphine (2.57 mg, 9.79 μmol, Eq: 0.01), bis(triphenylphosphine)palladium(II) chloride (6.87 mg, 9.79 μmol, Eq: 0.01) and ethynyltrimethylsilane (192 mg, 275 μl, 1.96 mmol, Eq: 2) were added, the vial was purged with argon, capped again and stirred for one more day at 120° C. The crude material was applied on silica gel and purified by flash chromatography over a 20 g silica gel column using heptane/ethyl acetate 10-30% as eluent affording 1-ethyl-5-pyrrolidin-1-yl-3-trimethylsilanylethynyl-1H-[1,2,4]triazole (122 mg, 47.5%) as an orange oil. MS: m/z=263.4 (M+H+)

Workup

  1. customwas purged for 5 minutes with nitrogen
  2. customthe vessel was capped
  3. customthe vial was purged with argon
  4. customcapped again
  5. custompurified by flash chromatography over a 20 g silica gel column

Sources & evidence

ORD record
ord-08e4f151ec864d52980b69b344630bf0
Source dataset
uspto-grants-2016_07
Patent number
US09394311B2

Reaction notes

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