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

HRID 1160004노트

반응식

HRID 1160004 반응식
[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

참가 물질

6

반응물 2

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

생성물 1

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

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 8028Tetrahydrofuran용매2회

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온도
60 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-6f3e4ed9bfd9484cbbe15b1382513896
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07812022B2

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