Lithium Chloride → Ethyl 2-(2-acetamidopyridin-4-yl)-4-bromothiazole-5-carboxylate

HRID 2402106Notes

Reaction equation

HRID 2402106 reaction equation
Br[C:2]1[S:3][C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:5]([Br:7])[N:6]=1.C[Sn](C)(C)[C:15]1[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22](=[O:24])[CH3:23])[CH:16]=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>[C:22]([NH:21][C:17]1[CH:16]=[C:15]([C:2]2[S:3][C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:5]([Br:7])[N:6]=2)[CH:20]=[CH:19][N:18]=1)(=[O:24])[CH3:23]

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 59529632N-(4-(trimethylstannyl)pyridin-2-yl)acetamideHCID 66747450Ethyl 2,4-dibromothiazole-5-carboxylate

Product 1

HCID 66747706Ethyl 2-(2-acetamidopyridin-4-yl)-4-bromothiazole-5-carboxylateYield 53%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of ethyl 2,4-dibromothiazole-5-carboxylate (0.500 g, 1.59 mmol), N-(4-(trimethylstannyl)pyridin-2-yl)acetamide (0.569 g, 1.90 mmol), tetrakis(triphenylphosphine)palladium(0) (91.7 mg, 0.0794 mmol), copper(I) iodide (90.7 mg, 0.476 mmol), and lithium chloride (202 mg, 4.76 mmol) in dioxane (29.1 mL) was degassed with nitrogen and heated at reflux for 1 hr. The reaction was cooled and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/hexane=0/100→50/50) to give 312 mg of the title compound. (44% yield). LC/MS (FA) ES+ 370, 372. 1H NMR (400 MHz, CDCl3) δ: 8.71 (s, 1H), 8.39 (d, 1H, J=5.2 Hz), 8.25 (bs, 1H), 7.68 (dd, 1H, J=5.2, 1.6 Hz), 4.41 (q, 2H, J=7.2 Hz), 2.26 (s, 3H), 1.41 (t, 3H, J=7.2 Hz).

Workup

  1. customwas degassed with nitrogen
  2. temperatureheated
  3. temperatureat reflux for 1 hr
  4. temperatureThe reaction was cooled
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (ethyl acetate/hexane=0/100→50/50)

Sources & evidence

ORD record
ord-efd2d47bec5b4c8faf957a14531124c1
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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