1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-t-butoxy-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide

HRID 18974

Reaktionsgleichung

Reaktionsgleichung von HRID 18974
[C:1]([O:5][CH2:6][CH:7]([N:11]1[CH2:15][C:14]([O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[O:23][CH3:24])=[CH:13][C:12]1=[O:25])[C:8]([OH:10])=O)([CH3:4])([CH3:3])[CH3:2].CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:47][C:48]1[CH:52]=[CH:51][N:50]([CH2:53][C:54]([CH3:57])([OH:56])[CH3:55])[N:49]=1>ClCCl>[C:1]([O:5][CH2:6][CH:7]([N:11]1[CH2:15][C:14]([O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[O:23][CH3:24])=[CH:13][C:12]1=[O:25])[C:8]([NH:47][C:48]1[CH:52]=[CH:51][N:50]([CH2:53][C:54]([OH:56])([CH3:55])[CH3:57])[N:49]=1)=[O:10])([CH3:3])([CH3:4])[CH3:2]

Komponenten

6

Edukt 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-olHCID 668946743-t-Butoxy-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid

Produkt 1

HCID 579200733-t-butoxy-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamideAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

A solution of 3-t-butoxy-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid (100 mg, 0.29 mmol) in dichloromethane (10 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (45 mg, 0.29 mmol) and 1-hydroxybenzotriazole (40 mg, 0.30 mmol). The reaction mixture was stirred at 25° C. for 2 h followed by the addition of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 50 mg, 0.32 mmol). The reaction mixture was then stirred for 18 h at 25° C., under nitrogen. The reaction mixture was diluted with dichloromethane, washed with 2N aqueous hydrochloric acid, saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over magnesium sulfate. The organic layer was concentrated, and the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 100% ethyl acetate/hexanes) to afford 3-t-butoxy-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide (45 mg, 32%) as an off-white solid: LR-ES-MS m/z calculated for C25H34N4O6 [M]+ 486, observed [M+H]+ 487; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.05 (s, 6H) 1.12 (s, 9H) 3.64-3.78 (m, 2H) 3.81 (s, 3H) 3.89 (s, 2H) 4.15 (d, J=18.4 Hz, 1H) 4.45 (d, J=18.4 Hz, 1H) 4.67 (s, 1H) 4.73 (s, 1H) 4.80 (dd, J=7.1, 4.7 Hz, 1H) 6.43 (d, J=2.2 Hz, 1H) 6.94-7.09 (m, 1H) 7.13-7.39 (m, 3H) 7.53 (d, J=2.2 Hz, 1H) 10.64 (s, 1H).

Aufarbeitung

  1. stirringThe reaction mixture was then stirred for 18 h at 25° C., under nitrogen
  2. washwashed with 2N aqueous hydrochloric acid, saturated sodium bicarbonate solution
  3. dry with materiala saturated sodium chloride solution and dried over magnesium sulfate
  4. concentrationThe organic layer was concentrated
  5. customthe crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 100% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-ec6d24b8ddb04eeead884ea569df34ad
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741327B2

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