Acetyl chloride → (R)-3-(4-(5-(4-((tert-butoxycarbonyl)amino)phenyl)-1,2,4-oxadiazol-3-yl)-3-fluorophenyl)-2-(5-(4-isopropylphenyl)furan-2-carboxamido)propanoic acid

HRID 405029ノート

反応式

HRID 405029 の反応式
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:19][N:18]=[C:17]([C:20]3[CH:25]=[CH:24][C:23]([CH2:26][C@@H:27]([NH:32][C:33]([C:35]4[O:36][C:37]([C:40]5[CH:45]=[CH:44][C:43]([CH:46]([CH3:48])[CH3:47])=[CH:42][CH:41]=5)=[CH:38][CH:39]=4)=[O:34])[C:28]([O:30]C)=[O:29])=[CH:22][C:21]=3[F:49])[N:16]=2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].S(Cl)(Cl)=O.C(C1C=CC(C2C=COC=2C(O)=O)=CC=1)(C)C.C(Cl)(=O)C.C(OC(=O)C(N)CC1C=CC(C2N=C(C3C=CC(NC(OC(C)(C)C)=O)=CC=3)ON=2)=C(F)C=1)C>>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[O:19][N:18]=[C:17]([C:20]3[CH:25]=[CH:24][C:23]([CH2:26][C@@H:27]([NH:32][C:33]([C:35]4[O:36][C:37]([C:40]5[CH:45]=[CH:44][C:43]([CH:46]([CH3:47])[CH3:48])=[CH:42][CH:41]=5)=[CH:38][CH:39]=4)=[O:34])[C:28]([OH:30])=[O:29])=[CH:22][C:21]=3[F:49])[N:16]=2)=[CH:13][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 5

HCID 6367Acetyl chlorideHCID 24386Thionyl ChlorideHCID 23062428p-Isopropylphenyl-furan-2-carboxylic acidHCID 66630730Ethyl 2-amino-3-(4-(5-(4-((tert-butoxycarbonyl)amino)phenyl)-1,2,4-oxadiazol-3-yl)-3-fluorophenyl)propanoateHCID 66630782(R)-methyl 3-(4-(5-(4-((tert-butoxycarbonyl)amino)phenyl)-1,2,4-oxadiazol-3-yl)-3-fluorophenyl)-2-(5-(4-isopropylphenyl)furan-2-carboxamido)propanoate

生成物 1

HCID 66630828(R)-3-(4-(5-(4-((tert-butoxycarbonyl)amino)phenyl)-1,2,4-oxadiazol-3-yl)-3-fluorophenyl)-2-(5-(4-isopropylphenyl)furan-2-carboxamido)propanoic acid

実験手順

(R)-methyl 3-(4-(5-(4-((tert-butoxycarbonyl)amino)phenyl)-1,2,4-oxadiazol-3-yl)-3-fluorophenyl)-2-(5-(4-isopropylphenyl)furan-2-carboxamido)propanoate. Thionyl chloride (5 mL) was added to p-isopropylphenyl-furan-2-carboxylic acid (1.7 g, 7.23 mmol) and the mixture was heated under reflux for 10 min. After removal of excess thionyl chloride under vacuum, the resulting acetyl chloride was added to the mixture of 2-amino-3-{4-[5-(4-tert-butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluorophenyl}-propionic acid ethyl ester (3 g, 6.58 mmol), disopropylethylamine (1.3 g, 9.87 mmol) and the mixture was stirred for 30 min at room temperature. The mixture was partitioned between EtOAc and water. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure to give the crude product, which was chromatographed on silica gel to give the title compound as a yellow solid (2.94 g).

後処理

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 10 min
  3. customAfter removal of excess thionyl chloride under vacuum
  4. customThe mixture was partitioned between EtOAc and water
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude product, which
  9. customwas chromatographed on silica gel

出典と根拠

ORDレコード
ord-c46269b32b0d4a958d52d2aad6d08fc2
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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