2,4-Dichloropyrimidine → N-[5-[(2-Chloro-4-pyrimidinyl)ethynyl]-2-(methyloxy)phenyl]-2,2,2-trifluoroacetamide

HRID 1160004ノート

反応式

HRID 1160004 の反応式
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[C:9]([C:11]1[CH:12]=[CH:13][C:14]([O:24][CH3:25])=[C:15]([NH:17][C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])[CH:16]=1)#[CH:10]>C1COCC1.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.[Cu]I>[Cl:1][C:2]1[N:7]=[C:6]([C:10]#[C:9][C:11]2[CH:12]=[CH:13][C:14]([O:24][CH3:25])=[C:15]([NH:17][C:18](=[O:23])[C:19]([F:20])([F:21])[F:22])[CH:16]=2)[CH:5]=[CH:4][N:3]=1

参加物

6

反応物 2

HCID 775312,4-DichloropyrimidineHCID 59511434N-[5-ethynyl-2-(methyloxy)phenyl]-2,2,2-trifluoroacetamide

生成物 1

HCID 59511410N-[5-[(2-Chloro-4-pyrimidinyl)ethynyl]-2-(methyloxy)phenyl]-2,2,2-trifluoroacetamide収率 83.1%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
60 °C

実験手順

To an oven-dried flask under N2 was added 2,4-dichloropyrimidine (860 mg, 5.76 mmol), anhydrous degassed THF (100 mL), dichlorobis(triphenylphosphine)palladium(II) (81 mg, 0.12 mmol), copper(I) iodide (13 mg, 0.07 mmol), and TEA (1.26 g, 0.013 mol). After heating the reaction at 60° C. for 30 min, N-[5-ethynyl-2-(methyloxy)phenyl]-2,2,2-trifluoroacetamide (560 mg, 2.30 mmol, obtained from composite batches) was added dropwise as a solution in THF (10 mL) and the resulting mixture was allowed to heat overnight at 60° C. The crude reaction mixture was adsorbed to silica gel and purified by column chromatography (0-10% EtOAc in hexanes) to afford the desired product (0.68 g, 42%) as an off white solid. ESIMS (M+H)+=356.

後処理

  1. temperatureAfter heating
  2. customthe reaction at 60° C. for 30 min
  3. customThe crude reaction mixture
  4. custompurified by column chromatography (0-10% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-6f3e4ed9bfd9484cbbe15b1382513896
出典データセット
uspto-grants-2010_10
特許番号
US07812022B2

反応ノート

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