Oxalyl chloride → (S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-N-pyrazin-2-yl-propionamide

HRID 18956

Reaktionsgleichung

Reaktionsgleichung von HRID 18956
[CH:1]1([CH2:6][C@H:7]([N:11]2[CH2:15][C:14]([O:16][CH3:17])=[CH:13][C:12]2=[O:18])[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[N:25]1[CH:30]=[CH:29][N:28]=[CH:27][C:26]=1[NH2:31].C(N(CC)C(C)C)(C)C>C1C=CC=CC=1.CN(C)C=O.ClCCl>[CH:1]1([CH2:6][C@H:7]([N:11]2[CH2:15][C:14]([O:16][CH3:17])=[CH:13][C:12]2=[O:18])[C:8]([NH:31][C:26]2[CH:27]=[N:28][CH:29]=[CH:30][N:25]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Komponenten

8

Edukt 4

HCID 65578Oxalyl chlorideHCID 78747AminopyrazineHCID 81531DiisopropylethylamineHCID 66894643(S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid

Produkt 1

HCID 44253056(S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-N-pyrazin-2-yl-propionamideAusbeute 3,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideKatalysatorHCID 241BenzeneLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

A solution of (S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid (prepared as in Example 1, 106 mg, 0.41 mmol) in benzene (10 mL) was treated with oxalyl chloride (55 mg, 0.43 mmol), and N,N-dimethylformamide (1 drop). Effervescence was observed. The reaction mixture was stirred for 2 h at 25° C., under nitrogen. The reaction mixture was concentrated, and dissolved in dichloromethane (10 mL) and treated with pyrazin-2-ylamine (42 mg, 0.43 mmol), and N,N-diisopropylethylamine (161 mg, 1.23 mmol). The reaction mixture was stirred at 25° C., under nitrogen for 18 h. The reaction mixture was diluted with dichloromethane, washed with 2N aqueous hydrochloric acid, saturated sodium chloride solution and dried. The organic layer was concentrated, and the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 4 g; 0% to 10% methanol/dichloromethane) to afford (S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-N-pyrazin-2-yl-propionamide (5 mg, 3%) as a white solid: LR-ES-MS m/z calculated for C17H22N4O3 [M]+ 330, observed [M+H]+ 331; 1H NMR (400 MHz, CDCl3) δ ppm 1.13-1.23 (m, 2H) 1.48-1.98 (m, 8H) 1.98-2.09 (m, 1H) 3.82 (s, 3H) 3.94 (d, J=17.5 Hz, 1H) 4.03 (d, J=17.5 Hz, 1H) 4.83 (dd, J=9.1, 6.5 Hz, 1H) 5.15 (s, 1H) 8.28 (dd, J=2.6, 1.5 Hz, 1H) 8.33 (d, J=2.6 Hz, 1H) 9.09 (s, 1H) 9.47 (d, J=1.5 Hz, 1H).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. dissolutiondissolved in dichloromethane (10 mL)
  3. stirringThe reaction mixture was stirred at 25° C., under nitrogen for 18 h
  4. washwashed with 2N aqueous hydrochloric acid, saturated sodium chloride solution
  5. customdried
  6. concentrationThe organic layer was concentrated
  7. customthe crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 4 g; 0% to 10% methanol/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-29abd0e6fe244451bdfbfb51f1437968
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741327B2

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