Lithium Chloride → Ethyl 5-[2-(acetylamino)pyridin-4-yl]-4-cyano-3-iodothiophene-2-carboxylate

HRID 2401972Notes

Reaction equation

HRID 2401972 reaction equation
[C:1]([C:3]1[C:4]([I:14])=[C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[S:6][C:7]=1I)#[N:2].C[Sn](C)(C)[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24](=[O:26])[CH3:25])[CH:18]=1.[Cl-].[Li+]>O1CCOCC1.[Cu]I.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>[C:24]([NH:23][C:19]1[CH:18]=[C:17]([C:7]2[S:6][C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:4]([I:14])[C:3]=2[C:1]#[N:2])[CH:22]=[CH:21][N:20]=1)(=[O:26])[CH3:25]

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 59529632N-(4-(trimethylstannyl)pyridin-2-yl)acetamideHCID 66748000Ethyl 4-cyano-3,5-diiodothiophene-2-carboxylate

Product 1

HCID 66747307Ethyl 5-[2-(acetylamino)pyridin-4-yl]-4-cyano-3-iodothiophene-2-carboxylateYield 65%

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
110 °C

Procedure

To a solution of ethyl 4-cyano-3,5-diiodothiophene-2-carboxylate (0.473 g, 1.09 mmol) and N-[4-(trimethylstannyl)pyridin-2-yl]acetamide (0.392 g, 1.31 mmol) in dioxane (10.2 mL) was added lithium chloride (0.139 g, 3.28 mmol), copper(I) iodide (0.0624 g, 0.328 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.0947 g, 0.0819 mmol). The reaction flask was evacuated and backfilled with argon, then the solution was heated at 110° C. for 2 hours. The mixture was cooled to room temperature and a mixture of dichloromethane and methanol was added until almost all solids had dissolved. The suspension was filtered through celite and the filtrate was evaporated. Column chromatography was performed to yield the title compound (0.312 g, 65%). LCMS: (FA) ES+ 442. 1H NMR (400 MHz, d6-DMSO) δ: 8.54-8.49 (m, 2H), 8.31 (s, 1H), 4.38-4.32 (m, 2H), 2.13 (s, 3H), 1.36-1.29 (m, 3H).

Workup

  1. customThe reaction flask was evacuated
  2. temperatureThe mixture was cooled to room temperature
  3. additiona mixture of dichloromethane and methanol
  4. additionwas added until almost all solids
  5. dissolutionhad dissolved
  6. filtrationThe suspension was filtered through celite
  7. customthe filtrate was evaporated

Sources & evidence

ORD record
ord-71d69a61b54742efac7b8b09db7d0aa4
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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