1-(2-Ethynylphenyl)cyclopropanecarboxamide → 1-(2-((2-((6-Methoxypyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxamide

HRID 592479Notes

Reaction equation

HRID 592479 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[C:16]1[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]2[CH:28]=[N:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=2)[N:17]=1>CN(C=O)C.[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>[CH3:34][O:33][C:30]1[N:29]=[CH:28][C:27]([NH:26][C:18]2[N:17]=[C:16]([C:2]#[C:1][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[C:9]3([C:12]([NH2:14])=[O:13])[CH2:11][CH2:10]3)[C:21]([C:22]([F:25])([F:23])[F:24])=[CH:20][N:19]=2)=[CH:32][CH:31]=1

Participants

6

Reactant 2

HCID 867122761-(2-Ethynylphenyl)cyclopropanecarboxamideHCID 867123404-Chloro-N-(6-methoxypyridin-3-yl)-5-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 867123441-(2-((2-((6-Methoxypyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-(2-ethynylphenyl)cyclopropanecarboxamide K6 (0.120 g, 0.648 mmol), 4-chloro-N-(6-methoxypyridin-3-yl)-5-(trifluoromethyl)pyrimidin-2-amine A68 (0.197 g, 0.648 mmol), CuI (0.012 g, 0.065 mmol), t-Bu3PHBF4 (0.019 g, 0.065 mmol) and PdCl2(PPh3)2 (0.023 g, 0.032 mmol) in DMF (3 mL) was bubbled with N2 for 5 minutes. Et3N (1 mL) was added and the reaction mixture was stirred in the microwave at 120° C. for 15 minutes. The volatiles were removed in vacuo and the black residue was adsorbed onto silica. Purification by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) gave the title compound A73 as a yellow solid (0.229 g, 78%). LCMS-D: rt 3.47 min; m/z 454 [M+H]+.

Workup

  1. customwas bubbled with N2 for 5 minutes
  2. additionEt3N (1 mL) was added
  3. customThe volatiles were removed in vacuo
  4. customPurification by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-d42f716e13ea45f4a81b1f140bb527ec
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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