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 405018Notes

Reaction equation

HRID 405018 reaction equation
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]

Participants

5

Reactant 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

Product 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 acidYield 72.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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)−.

Workup

  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)

Sources & evidence

ORD record
ord-d7ffd9227bdd45059977a2022ae53560
Source dataset
uspto-grants-2014_06
Patent number
US08748412B2

Reaction notes

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