Triethylamine → 2-(2-((2-Chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)acetamide

HRID 1778954Notes

Reaction equation

HRID 1778954 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([NH2:12])=[O:11])#[CH:2].[Cl:13][C:14]1[N:19]=[C:18](Cl)[C:17]([CH3:21])=[CH:16][N:15]=1.CCN(CC)CC>O1CCOCC1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:13][C:14]1[N:19]=[C:18]([C:2]#[C:1][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[CH2:9][C:10]([NH2:12])=[O:11])[C:17]([CH3:21])=[CH:16][N:15]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 74508Pyrimidine, 2,4-dichloro-5-methyl-HCID 533429972-(2-Ethynylphenyl)acetamide

Product 1

HCID 867126232-(2-((2-Chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)acetamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-(2-ethynylphenyl)acetamide (I8) (5.40 g, 33.9 mmol), 2,4-dichloro-5-methylpyrimidine (6.63 g, 40.7 mmol) and CuI (0.129 g, 0.678 mmol) in 1,4-dioxane (180 mL) and Et3N (14.2 mL, 101 mmol) was placed under nitrogen. PdCl2(PPh3)2 (0.238 g, 0.339 mmol) was added and the resulting mixture was stirred at 70° C. for 20 minutes, then adsorbed onto silica gel and purified by column chromatography (CombiFlash Rf, 120 g SiO2 Cartridge, 0-5% MeOH in DCM) to give the title compound I9 as a yellow solid (5.01 g, 51%); 1H NMR (300 MHz, d6-DMSO) δ 8.75 (s, 1H), 7.67 (d, J=7.5 Hz, 1H), 7.35-7.52 (m, 4H), 6.97 (brs, 1H), 3.71 (s, 2H), 2.42 (s, 3H). LCMS-B: rt 5.689 min; m/z 286 [M+H]+.

Workup

  1. custompurified by column chromatography (CombiFlash Rf, 120 g SiO2 Cartridge, 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-a3dc32652cb44cf899ad67c36ff88d35
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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