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

HRID 2402052Notes

Reaction equation

HRID 2402052 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%

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 (13.6 g, 31.0 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 (1.77 g, 9.30 mmol) and lithium chloride (3.94 g, 93.0 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 h. The solvent was evaporated and the crude reaction mixture was purified by ISCO chromatography (0 to 3% MeOH in DCM). Product was obtained as an orange solid (10.1 g, 66.0%). LCMS: (AA) ES+, 494, 496. 1H NMR (300 MHz, CDCl3) 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. customThe solvent was evaporated
  4. customthe crude reaction mixture
  5. customwas purified by ISCO chromatography (0 to 3% MeOH in DCM)

Sources & evidence

ORD record
ord-14e7c00ad03944018b02788834e0569e
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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