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Pyrimidine, 2,4-dichloro-5-methyl- → 1-(2-((2-Chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxamide

HRID 592433
Notes
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Reaction equation

HRID 592433 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1([C:12]([NH2:14])=[O:13])[CH2:11][CH2:10]1)#[CH:2].[Cl:15][C:16]1[N:21]=[C:20](Cl)[C:19]([CH3:23])=[CH:18][N:17]=1>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:15][C:16]1[N:21]=[C:20]([C:2]#[C:1][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[C:9]2([C:12]([NH2:14])=[O:13])[CH2:11][CH2:10]2)[C:19]([CH3:23])=[CH:18][N:17]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 2

HCID 74508Pyrimidine, 2,4-dichloro-5-methyl-HCID 867122761-(2-Ethynylphenyl)cyclopropanecarboxamide

Product 1

HCID 867123141-(2-((2-Chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxamide

Reagents, catalysts & solvents 3

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

Conditions

Temperature
70 °C

Procedure

A mixture of 1-(2-ethynylphenyl)cyclopropanecarboxamide K6 (2.29 g, 12.4 mmol), 2,4-dichloro-5-methylpyrimidine (2.62 g, 16.1 mmol), CuI (0.047 g, 0.25 mmol) and PdCl2(PPh3)2 (0.087 g, 0.12 mmol) in dioxane (25 mL) was bubbled with N2 for 10 minutes. Et3N (10 mL) was added and the mixture was stirred under nitrogen at 70° C. for 1 hour. The reaction mixture was cooled and adsorbed onto silica. Purification by column chromatography (Biotage Isolera, 120 g SiO2, 0-10% MeOH in CHCl3) gave the title compound A39 as a yellow oil (1.85 g, 48%). LCMS-D: rt 3.24 min; m/z 312 [M+H]+.

Workup

  1. customwas bubbled with N2 for 10 minutes
  2. additionEt3N (10 mL) was added
  3. temperatureThe reaction mixture was cooled
  4. customPurification by column chromatography (Biotage Isolera, 120 g SiO2, 0-10% MeOH in CHCl3)

Sources & evidence

ORD record
ord-a3d6234abfbe40be84b48befb5e708ff
Source dataset
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09238644B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes