Morpholine → 3-{4-[5-(4-tert-Butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluoro-phenyl}-2-[(5-p-tolyl-furan-2-carbonyl)-amino]-propionic acid

HRID 405018Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 405018
C(O[C:4](=O)[CH:5](N)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2N=C(C3C=CC(NC(OC(C)(C)C)=O)=CC=3)ON=2)=[C:9](F)[CH:8]=1)C.C([O:37][C:38](=[O:85])[CH:39]([NH:67][C:68](OCC1C2C=CC=CC=2C2C1=CC=CC=2)=[O:69])[CH2:40][C:41]1[CH:46]=[CH:45][C:44]([C:47]2[N:51]=[C:50]([C:52]3[CH:57]=[CH:56][C:55]([NH:58][C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[CH:54][CH:53]=3)[O:49][N:48]=2)=[C:43]([F:66])[CH:42]=1)C.N1CC[O:89][CH2:88]C1>CN(C=O)C>[C:62]([O:61][C:59]([NH:58][C:55]1[CH:56]=[CH:57][C:52]([C:50]2[O:49][N:48]=[C:47]([C:44]3[CH:45]=[CH:46][C:41]([CH2:40][CH:39]([NH:67][C:68]([C:88]4[O:89][C:6]([C:7]5[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][CH:12]=5)=[CH:5][CH:4]=4)=[O:69])[C:38]([OH:37])=[O:85])=[CH:42][C:43]=3[F:66])[N:51]=2)=[CH:53][CH:54]=1)=[O:60])([CH3:65])([CH3:64])[CH3:63]

Komponenten

5

Edukt 3

HCID 8083MorpholineHCID 66630730Ethyl 2-amino-3-(4-(5-(4-((tert-butoxycarbonyl)amino)phenyl)-1,2,4-oxadiazol-3-yl)-3-fluorophenyl)propanoateHCID 666309633-{4-[5-(4-tert-butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluorophenyl}-2-(9H-fluoren-9-ylmethoxycarbonylamino)propionic acid ethyl ester

Produkt 1

HCID 533745103-{4-[5-(4-tert-Butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluoro-phenyl}-2-[(5-p-tolyl-furan-2-carbonyl)-amino]-propionic acidAusbeute 72,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

2-Amino-3-{4-[5-(4-tert-butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluorophenyl}propionic acid ethyl ester. To a stirring solution of 3-{4-[5-(4-tert-butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluorophenyl}-2-(9H-fluoren-9-ylmethoxycarbonylamino)propionic acid ethyl ester (8.25 g, 12 mol) in DMF (10 mL) was added morpholine (30 mL). The solution was stirred for 2 hrs at room temperature. The solution was then concentrated and extracted with EtOAc (3×100 mL). The combined organic layers were washed sequentially with brine and dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude was purified by column chromatography (PE/EtOAc, 2/1) to give the title compound (4.1 g, 72.7% yield) as a light yellow solid. 1H-NMR (400 MHz, DMSO-d6): δ 9.91 (s, 1H), 8.08 (d, J=8.8 Hz, 2H), 7.99 (t, J=8.0 Hz, 1H), 7.32 (d, J=8.8 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 4.02-4.08 (m, 2H), 3.63 (t, J=6.8 Hz, 1H), 2.85-2.99 (m, 2H), 1.50 (s, 9H), 1.13 (t, J=6.8 Hz, 3H); EI-MS (m/z): 469 (M−H)−.

Aufarbeitung

  1. concentrationThe solution was then concentrated
  2. extractionextracted with EtOAc (3×100 mL)
  3. washThe combined organic layers were washed sequentially with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude was purified by column chromatography (PE/EtOAc, 2/1)

Quellen und Nachweise

ORD-Eintrag
ord-d7ffd9227bdd45059977a2022ae53560
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08748412B2

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