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 405018ノート

反応式

HRID 405018 の反応式
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]

参加物

5

反応物 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

生成物 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 acid収率 72.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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)−.

後処理

  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)

出典と根拠

ORDレコード
ord-d7ffd9227bdd45059977a2022ae53560
出典データセット
uspto-grants-2014_06
特許番号
US08748412B2

反応ノート

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