Lithium Chloride → N-{4-[5-(1-benzyl-1H-imidazol-2-yl)-3-cyano-4-(2,4-dichlorophenyl)-2-thienyl]pyridin-2-yl}acetamide

HRID 2282128Notes

Reaction equation

HRID 2282128 reaction equation
[CH2:1]([N:8]1[CH:12]=[CH:11][N:10]=[C:9]1[C:13]1[S:17][C:16](Br)=[C:15]([C:19]#[N:20])[C:14]=1[C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=1[Cl:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Sn](C)(C)[C:31]1[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38](=[O:40])[CH3:39])[CH:32]=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>[CH2:1]([N:8]1[CH:12]=[CH:11][N:10]=[C:9]1[C:13]1[S:17][C:16]([C:31]2[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38](=[O:40])[CH3:39])[CH:32]=2)=[C:15]([C:19]#[N:20])[C:14]=1[C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=1[Cl:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 59529632N-(4-(trimethylstannyl)pyridin-2-yl)acetamideHCID 668562415-(1-benzyl-1H-imidazol-2-yl)-2-bromo-4-(2,4-dichlorophenyl)thiophene-3-carbonitrile

Product 1

HCID 46866367N-{4-[5-(1-benzyl-1H-imidazol-2-yl)-3-cyano-4-(2,4-dichlorophenyl)-2-thienyl]pyridin-2-yl}acetamideYield 60%

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
90 °C

Procedure

5-(1-benzyl-1H-imidazol-2-yl)-2-bromo-4-(2,4-dichlorophenyl)thiophene-3-carbonitrile (107 mg, 0.219 mmol), N-[4-(trimethylstannyl)pyridin-2-yl]acetamide (85.0 mg, 0.284 mmol), Lithium chloride (30.0 mg, 0.708 mmol), Copper(I) iodide (4.70 mg, 0.0247 mmol) and Tetrakis(triphenylphosphine)palladium(0) (24.7 mg, 0.0214 mmol) were taken up in 1,4-Dioxane (3.0 mL) under an atmosphere of argon. The mixture was heated at 90° C. for 4 hours. The solvent was evaporated and the residue was purified using ISCO chromatography on silica gel, elution with 1-2% MeOH in DCM to give the product (0.071 g, 60%). LCMS: (FA) ES+ 544, 546. 1H NMR (400 MHz, d1-chloroform) δ: 8.59 (s, 1H), 8.40 (d, J=5.27 Hz, 1H), 8.03 (s, 1H), 7.52 (dd, J=5.27 Hz, 1.76 Hz, 1H), 7.30 (d, J=2.00 Hz, 1H), 7.27-7.16 (m, 6H), 6.87 (d, 1H), 6.77-6.75 (d, J=6.27 Hz, 2H), 4.90-4.78 (m, 2H), 2.25 (s, 3H).

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified
  3. washon silica gel, elution with 1-2% MeOH in DCM

Sources & evidence

ORD record
ord-c0d127220306451283ae88edb7b2bbad
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

Loading…