Lithium Chloride → N-{4-[4-bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]pyridin-2-yl}acetamide

HRID 2282308Notes

Reaction equation

HRID 2282308 reaction equation
Br[C:2]1[S:3][C:4]([C:8]2[N:12]=[CH:11][N:10]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:9]=2)=[C:5]([Br:7])[N:6]=1.C[Sn](C)(C)[C:23]1[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30](=[O:32])[CH3:31])[CH:24]=1.[Cl-].[Li+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Cu]I>[Br:7][C:5]1[N:6]=[C:2]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30](=[O:32])[CH3:31])[CH:24]=2)[S:3][C:4]=1[C:8]1[N:12]=[CH:11][N:10]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:9]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 580950363-(2,4-dibromo-1,3-thiazol-5-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazoleHCID 59529632N-(4-(trimethylstannyl)pyridin-2-yl)acetamide

Product 1

HCID 58095236N-{4-[4-bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]pyridin-2-yl}acetamideYield 13%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

The mixture of 3-(2,4-dibromo-1,3-thiazol-5-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazole (1.10 g, 2.50 mmol), N-[4-(trimethylstannyl)pyridin-2-yl]acetamide (0.896 g, 3.00 mmol), tetrakis(triphenylphosphine)palladium (0) (0.155 g, 0.125 mmol), copper(I) iodide (0.143 g, 0.750 mmol) and lithium chloride (0.318 g, 7.50 mmol) in dry 1,4-Dioxane (100 mL) was sonicated for 2 min, degassed and backfilled with nitrogen for 5 times. The mixture was heated under nitrogen atmosphere to reflux for 90 min, cooled to room temperature, filtered thought celite and washed with dioxane/DCM. The filtrate was evaporated under reduced pressure to give a crude residue, which was purified using chromatography on a silica column using MeOH/DCM (0/100 to 5/95) to give a product, which was further purified on a silica column using MeOH/EtOAc/hexane (0/0/100 to 5/45/50) to give pure product (0.150 g, 13%). LCMS: (FA) ES+ 495, 497. 1H NMR (400 MHz, d1-chloroform) 8.72 (s, 1H), 8.37 (m, 1H), 8.33 (s, 1H), 8.26 (s, 1H), 7.68 (m, 1H), 5.57 (s, 2H), 3.73 (t, J=8.28 Hz, 2H), 2.25 (s, 3H), 0.97 (t, J=8.28 Hz, 2H), 0.00 (s, 9H).

Workup

  1. customwas sonicated for 2 min
  2. customdegassed
  3. temperatureThe mixture was heated under nitrogen atmosphere
  4. temperatureto reflux for 90 min
  5. filtrationfiltered
  6. washwashed with dioxane/DCM
  7. customThe filtrate was evaporated under reduced pressure
  8. customto give a crude residue, which
  9. customwas purified
  10. customto give a product, which
  11. customwas further purified on a silica column

Sources & evidence

ORD record
ord-e88f564a28a4424ebe1d44decb1301d5
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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