Lithium Chloride → N-(4-(4-bromo-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazol-2-yl)pyridin-2-yl)acetamide

HRID 2282302Notes

Reaction equation

HRID 2282302 reaction equation
Br[C:2]1[S:3][C:4]([C:8]2[N:9]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:10]=[CH:11][N:12]=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([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[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:9]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:10]=[CH:11][N:12]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 580947602,4-dibromo-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazoleHCID 59529632N-(4-(trimethylstannyl)pyridin-2-yl)acetamide

Product 1

HCID 58095120N-(4-(4-bromo-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazol-2-yl)pyridin-2-yl)acetamideYield 66.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2,4-dibromo-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazole (13.62 g, 31.01 mmol), N-[4-(trimethylstannyl)pyridin-2-yl]acetamide (11.1 g, 37.2 mmol), tetrakis(triphenylphosphine)palladium(0) (1.792 g, 1.550 mmol), copper(I) iodide (1.772 g, 9.302 mmol) and lithium chloride (3.944 g, 93.02 mmol) in 1,4-dioxane (569 mL) was degassed with argon. The mixture was sonicated for 20 min and then heated at 120° C. for 5 hrs. Solvent was evaporated and the crude reaction mixture was purified by ISCO chromatography, eluted with MeOH in DCM, 0-3%. Product was obtained as an orange solid (10.13 g, 66.0%). LCMS: (AA) ES+, 494, 496. NMR (300 MHz, d1-chloroform) δ: 8.65 (s, 1H) 8.44 (br, 1H) 8.34 (d, 1H) 7.60 (dd, 1H) 7.30 (d, 2H) 5.30 (s, 2H) 3.40 (t, 2H) 2.25 (s, 3H) 0.86 (t, 2H) −0.05 (s, 9H).

Workup

  1. customwas degassed with argon
  2. customThe mixture was sonicated for 20 min
  3. customSolvent was evaporated
  4. customthe crude reaction mixture
  5. customwas purified by ISCO chromatography
  6. washeluted with MeOH in DCM, 0-3%

Sources & evidence

ORD record
ord-7a8f2e55826648469ab468386546a8e2
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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