1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Biphenyl-4-carboxylic acid {2-[4-(2-fluoro-6-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide

HRID 1177985

Reaktionsgleichung

Reaktionsgleichung von HRID 1177985
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[C:12]=1[C:13]([OH:15])=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[O:45]=[C:46]([N:63]1[CH2:68][CH2:67][NH:66][CH2:65][CH2:64]1)[CH2:47][NH:48][C:49]([C:51]1[CH:56]=[CH:55][C:54]([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)=[CH:53][CH:52]=1)=[O:50]>CN(C=O)C.O>[F:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[C:12]=1[C:13]([N:66]1[CH2:65][CH2:64][N:63]([C:46](=[O:45])[CH2:47][NH:48][C:49]([C:51]2[CH:56]=[CH:55][C:54]([C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)=[CH:53][CH:52]=2)=[O:50])[CH2:68][CH2:67]1)=[O:15]

Komponenten

8

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 6881232-Fluoro-6-(trifluoromethyl)benzoic acidHCID 57855677Biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide

Produkt 1

HCID 59559608Biphenyl-4-carboxylic acid {2-[4-(2-fluoro-6-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amideAusbeute 50,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

DIPEA (118 mg, 0.16 mL, 0.92 mmol) was added to a stirred solution of 2-fluoro-6-trifluoromethyl-benzoic acid (48 mg, 0.23 mmol) in DMF (2 mL). HOBT (46 mg, 0.35 mmol) and EDCI (100 mg, 0.57 mmol) were then added at room temperature. After 2 minutes, Biphenyl-4-carboxylic acid (2-oxo-2-piperazin-1-yl-ethyl)-amide (75 mg, 0.23 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the product was extracted with EtOAc and the organic layer was washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to get the residue. The obtained residue was purified by column chromatography (using basic alumina and 10% MeOH in CHCl3 as eluent) to afford 60 mg (50.8% yield) of biphenyl-4-carboxylic acid {2-[4-(2-fluoro-6-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LCMS Purity: 96.5%. 1H NMR (CDCl3): δ 7.9 (m, 2H), 7.6 (m, 6H), 7.4 (m, 4H), 4.3 (m, 2H), 3.8 (m, 3H), 3.8 (m, 3H), 3.6-(m, 2H), 3.5 (m, 1H) 3.3 (m, 2H).

Aufarbeitung

  1. extractionthe product was extracted with EtOAc
  2. washthe organic layer was washed with brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto get the residue
  6. customThe obtained residue was purified by column chromatography (using basic alumina and 10% MeOH in CHCl3 as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-3e3e9d6215ae4248a770f42918e1ca4b
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07842696B2

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