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 405029노트

반응식

HRID 405029 반응식
[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]

참가 물질

6

반응물 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

생성물 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

실험 절차

(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).

후처리

  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

출처 및 근거

ORD 기록
ord-c46269b32b0d4a958d52d2aad6d08fc2
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08748412B2

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