3-Methoxypropyne → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-methoxy-prop-1-ynyl)-pyrazin-2-yl]-propionamide

HRID 719949ノート

反応式

HRID 719949 の反応式
Br[C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9](=[O:28])[C@@H:10]([C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[C:19]([Cl:27])[CH:18]=2)[CH2:11][CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[N:6][CH:7]=1.C(N(CC)C(C)C)(C)C.[CH3:38][O:39][CH2:40][C:41]#[CH:42]>C1(C)C=CC=CC=1.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:27][C:19]1[CH:18]=[C:17]([C@@H:10]([CH2:11][CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[C:9]([NH:8][C:5]2[CH:4]=[N:3][C:2]([C:42]#[C:41][CH2:40][O:39][CH3:38])=[CH:7][N:6]=2)=[O:28])[CH:22]=[CH:21][C:20]=1[S:23]([CH3:26])(=[O:25])=[O:24]

参加物

7

反応物 3

HCID 693933-MethoxypropyneHCID 81531DiisopropylethylamineHCID 86593779N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

生成物 1

HCID 99824062(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-methoxy-prop-1-ynyl)-pyrazin-2-yl]-propionamide収率 69.5%

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 1140Toluene溶媒

反応条件

温度
25 °C

実験手順

A suspension of N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (prepared as in Example 6, 486 mg, 1.0 mmol) in toluene (8 mL) was treated with N,N-diisopropylethylamine (2 mL), 3-methoxypropyne (350 mg, 10.0 mmol), dichlorobis(triphenylphosphine)palladium(II) (40 mg), and copper(I) iodide (20 mg). The mixture was stirred at 25° C. overnight, and an oily black precipitate was obtained. The top clear solution was decanted, and the oily precipitate was rinsed with toluene (5 mL). The residue was dissolved in methylene chloride and extracted with methylene chloride and a 0.2N aqueous hydrochloric acid solution. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (1/3 to 1/2 ethyl acetate/hexane) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-methoxy-prop-1-ynyl)-pyrazin-2-yl]-propionamide (330 mg, 69.5%) as a fluffy solid: (ES)+-HRMS m/e calcd for C23H26ClN3O4S (M+H)+ 476.1406, found 476.1405.

後処理

  1. customan oily black precipitate was obtained
  2. customThe top clear solution was decanted
  3. washthe oily precipitate was rinsed with toluene (5 mL)
  4. dissolutionThe residue was dissolved in methylene chloride
  5. extractionextracted with methylene chloride
  6. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-2650fab7a013464589b1ca47815143f0
出典データセット
uspto-grants-2006_11
特許番号
US07132425B2

反応ノート

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