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Triethylamine → 4-[2-Cyclopropyl-1-(4-fluoro-phenyl)-1H-imidazol-4-ylethynyl]-2-methyl-pyridine

HRID 860155
ノート
印刷プレビュー

反応式

HRID 860155 の反応式
[CH:1]1([C:4]2[N:5]([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)[CH:6]=[C:7](I)[N:8]=2)[CH2:3][CH2:2]1.[CH3:17][C:18]1[CH:23]=[C:22]([C:24]#[C:25][Si](C)(C)C)[CH:21]=[CH:20][N:19]=1.C(N(CC)CC)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:1]1([C:4]2[N:5]([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)[CH:6]=[C:7]([C:25]#[C:24][C:22]3[CH:21]=[CH:20][N:19]=[C:18]([CH3:17])[CH:23]=3)[N:8]=2)[CH2:3][CH2:2]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

10

反応物 4

HCID 8471TriethylamineHCID 2724141Tetrabutylammonium FluorideHCID 219853962-Methyl-4-((trimethylsilyl)ethynyl)pyridineHCID 691201812-Cyclopropyl-1-(4-fluoro-phenyl)-4-iodo-1H-imidazole

生成物 1

HCID 100415194-[2-Cyclopropyl-1-(4-fluoro-phenyl)-1H-imidazol-4-ylethynyl]-2-methyl-pyridine収率 59%

試薬・触媒・溶媒 5

HCID 11776Triphenylphosphine触媒
HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒
HCID 6102075Dichlorobis(triphenylphosphine)palladium触媒
HCID 962Water溶媒
HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
40 °C

実験手順

2-Cyclopropyl-1-(4-fluoro-phenyl)-4-iodo-1H-imidazole (V-1) (150 mg, 0.46 mmol) and 2-methyl-4-trimethylsilanylethynyl-pyridine (113 mg, 0.59 mmol) were dissolved in 4 mL dry THF. This mixture was evacuated and backfilled with argon several times to remove oxygen from the solution. In a second reaction vessel triphenylphosphine (4 mg, 0.01 mmol), bis(triphenylphosphine)-palladium(II)chloride (16 mg, 0.02 mmol), copper(I)iodide (1 mg, 0.01 mmol) and triethyl amine (0.10 mL, 0.69 mmol) were dissolved in 2 mL dry THF. This mixture was also evacuated and backfilled with argon several times to remove oxygen from the solution. This mixture was heated to 40° C. and the solution of 2-cyclopropyl-1-(4-fluoro-phenyl)-4-iodo-1H-imidazole and 2-methyl-4-trimethylsilanylethynyl-pyridine was added dropwise. The reaction mixture was heated to 60° C. and tetrabutylammonium fluoride solution (1M in THF, 0.72 mL, 0.69 mmol) was added dropwise during 5 min. The reaction was than stirred at 40° C. for 2 hours. The mixture was taken up in 20 mL water and extracted three times with ethyl acetate (20 mL each). The combined organic extracts were dried with magnesium sulfate, filtered and evaporated. The crude product was purified by chromatography on silica gel (n-heptane/ethyl acetate 1:4) to obtain the desired title compound as a colorless solid (85 mg, 59%),

後処理

  1. customThis mixture was evacuated
  2. customto remove oxygen from the solution
  3. customThis mixture was also evacuated
  4. customto remove oxygen from the solution
  5. additionthe solution of 2-cyclopropyl-1-(4-fluoro-phenyl)-4-iodo-1H-imidazole and 2-methyl-4-trimethylsilanylethynyl-pyridine was added dropwise
  6. temperatureThe reaction mixture was heated to 60° C.
  7. extractionextracted three times with ethyl acetate (20 mL each)
  8. dry with materialThe combined organic extracts were dried with magnesium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was purified by chromatography on silica gel (n-heptane/ethyl acetate 1:4)

出典と根拠

ORDレコード
ord-79504f27139041e1a1d29206bcbe4bcb
出典データセット
uspto-grants-2006_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07153874B2

反応ノート

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