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

HRID 719949Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 719949
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]

Komponenten

7

Edukt 3

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

Produkt 1

HCID 99824062(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-methoxy-prop-1-ynyl)-pyrazin-2-yl]-propionamideAusbeute 69,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-2650fab7a013464589b1ca47815143f0
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07132425B2

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