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 405029Notes

Reaction equation

HRID 405029 reaction equation
[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]

Participants

6

Reactant 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

Product 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

Procedure

(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).

Workup

  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

Sources & evidence

ORD record
ord-c46269b32b0d4a958d52d2aad6d08fc2
Source dataset
uspto-grants-2014_06
Patent number
US08748412B2

Reaction notes

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