1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(2-oxo-pyrrolidin-1-yl)-N-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-benzamide

HRID 1093847Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1093847
CCN(C(C)C)C(C)C.[O:10]=[C:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16]1[CH:24]=[CH:23][C:19]([C:20]([OH:22])=O)=[CH:18][CH:17]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:47][CH2:48][C:49]([N:51]1[CH2:56][CH2:55][CH:54]([O:57][C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([C:64]([F:67])([F:66])[F:65])[CH:59]=2)[CH2:53][CH2:52]1)=[O:50]>CN(C=O)C.O>[O:10]=[C:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16]1[CH:17]=[CH:18][C:19]([C:20]([NH:47][CH2:48][C:49](=[O:50])[N:51]2[CH2:52][CH2:53][CH:54]([O:57][C:58]3[CH:63]=[CH:62][CH:61]=[C:60]([C:64]([F:65])([F:66])[F:67])[CH:59]=3)[CH2:55][CH2:56]2)=[O:22])=[CH:23][CH:24]=1

Komponenten

8

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7731304-(2-Oxopyrrolidin-1-yl)benzoic acidHCID 665915472-Amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride

Produkt 1

HCID 578744584-(2-oxo-pyrrolidin-1-yl)-N-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-benzamideAusbeute 56,62 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

DIPEA (200 mg, 1.55 mmol) was added to a stirred solution of 4-(2-oxo-pyrrolidin-1-yl)-benzoic acid (70 mg, 0.34 mmol) in DMF (5 mL) followed by HOBt (50 mg, 0.37 mmol) and EDCI (163 mg, 0.85 mmol). After 2 minutes of stirring, 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (127 mg, 0.37 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the precipitate was filtered off. The solid obtained was purified by column chromatography (using 60-120 silica gel and 70% ethyl acetate in hexane as eluent) to afford 94 mg (56.62% Yield) of 4-(2-oxo-pyrrolidin-1-yl)-N-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-benzamide. LC/MS [M+H]+: 490.19, 98.95%. 1H NMR (300 MHz, DMSO-d6): δ 8.6 (t, 1H), 7.94 (d, 2H), 7.8 (d, 2H), 7.6 (t, 1H), 7.38 (t, 3H), 4.8 (m, 1H), 4.2 (d, 1H), 4.0 (t, 3H), 3.8 (d, 1H), 3.5 (d, 1H), 3.3 (bs, 1H), 2.5 (bs, 2H), 2.1 (m, 2H), 2.0 (d, 2H), 1.7 (d, 2H).

Aufarbeitung

  1. additionwas added
  2. stirringthe resulting mixture was stirred at room temperature overnight
  3. filtrationthe precipitate was filtered off
  4. customThe solid obtained
  5. customwas purified by column chromatography (using 60-120 silica gel and 70% ethyl acetate in hexane as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-002e95171c744cc99a25dcaa2b75d3e9
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08129376B2

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