Lithium Chloride → HCID 58094981, compound

HRID 2402458Notes

Reaction equation

HRID 2402458 reaction equation
[CH2:1]([N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[C:9]1[S:10][C:11](I)=[CH:12][C:13]=1[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[Cl:21])[CH:2]=[CH2:3].C[Sn](C)(C)[C:25]1[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32](=[O:34])[CH3:33])[CH:26]=1.[Li+].[Cl-]>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>[CH2:1]([N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[C:9]1[S:10][C:11]([C:25]2[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32](=[O:34])[CH3:33])[CH:26]=2)=[CH:12][C:13]=1[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[Cl:21])[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 58094757HCID 58094757, compoundHCID 59529632N-(4-(trimethylstannyl)pyridin-2-yl)acetamide

Product 1

HCID 58094981HCID 58094981, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

1-allyl-2-[3-(2,4-dichlorophenyl)-5-iodo-2-thienyl]-1H-imidazole (4) (2.00 g, 4.34 mmol), N-[4-(trimethylstannyl)pyridin-2-yl]acetamide (2.59 g, 8.67 mmol), tetrakis(triphenylphosphine)palladium (0.25 g, 0.22 mmol), CuI (0.25 g, 1.30 mmol), and LiCl (0.55 g, 13.0 mmol) were weighed into a round bottom flask, equipped with reflux condenser, and the flask was purged with Argon. To this mixture was added 1,4-dioxane (100 mL) and the resulting suspension was stirred for 5 hrs at 90° C. The reaction was cooled to room temperature and concentrated in vacuo. To the solid residue was added EtOAc and DCM then the suspension was filtered through a Celite pad. The filtrate was concentrated in vacuo and the residue was purified by column chromatography (SiO2, elution with 45% CH3CN: 50 DCM: 5% MeOH) to give crude product which was further purified by column chromatography (SiO2, elution with 4-7% MeOH in DCM) to provide 1.03 g of product (51%). LC/MS (FA) ES+ 471. 1H NMR (400 MHz, d6-DMSO) δ: 10.6 (s, 1H), 8.39 (s, 1H), 8.36 (d, J=5.3 Hz, 1H), 7.86 (s, 1H), 7.73 (d, J=2.3 Hz, 1H), 7.49 (dd, J=1.8, 5.3 Hz, 1H), 7.42 (dd, J=2.2, 8.3 Hz, 1H), 7.19-7.23 (m, 2H), 7.03 (d, J=1.1 Hz, 1H), 5.54-5.65 (m, 1H), 5.02-5.07 (m, 1H), 4.79-4.86 (m, 1H), 4.28-4.32 (m, 2H), 2.12 (s, 3H).

Workup

  1. customequipped
  2. temperaturewith reflux condenser
  3. customthe flask was purged with Argon
  4. additionTo this mixture was added 1,4-dioxane (100 mL)
  5. temperatureThe reaction was cooled to room temperature
  6. concentrationconcentrated in vacuo
  7. additionTo the solid residue was added EtOAc and DCM
  8. filtrationthe suspension was filtered through a Celite pad
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by column chromatography (SiO2, elution with 45% CH3CN: 50 DCM: 5% MeOH)
  11. customto give crude product which
  12. customwas further purified by column chromatography (SiO2, elution with 4-7% MeOH in DCM)

Sources & evidence

ORD record
ord-f7ac34f4159f497e828eca8b803c18b6
Source dataset
uspto-grants-2014_08
Patent number
US08796314B2

Reaction notes

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