Dimethylformamide → 2-(4-hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-acetamide

HRID 1178067

Reaktionsgleichung

Reaktionsgleichung von HRID 1178067
CCN(C(C)C)C(C)C.[OH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([NH:20][CH2:21][C:22]([OH:24])=O)=[O:19])=[CH:13][CH:12]=1.C1C=CC2N([OH:34])N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[N:48]1([C:54]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=2[C:62]([F:65])([F:64])[F:63])=[O:55])[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1.CN([CH:69]=[O:70])C>O>[F:63][C:62]([F:65])([F:64])[C:69]([OH:70])=[O:34].[OH:10][C:11]1[CH:12]=[CH:13][C:14]([CH2:17][C:18]([NH:20][CH2:21][C:22](=[O:24])[N:51]2[CH2:52][CH2:53][N:48]([C:54](=[O:55])[C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=3[C:62]([F:65])([F:63])[F:64])[CH2:49][CH2:50]2)=[O:19])=[CH:15][CH:16]=1

Komponenten

9

Edukt 6

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 4407324-HydroxyphenylacetylglycineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 167337831-(2-Trifluoromethylbenzoyl)piperazine hydrochloride

Produkt 2

HCID 6422Trifluoroacetic acidAusbeute 0,1 %HCID 595596192-(4-hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-acetamideAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

DIPEA (0.407 g, 0.545 mL, 3.15 mmol) was added to a stirred solution of [2-(4-Hydroxy-phenyl)-acetyl amino]-acetic acid (55 mg, 0.26 mmol) in DMF (5 mL). HOBT (39 mg, 2.8 mmol) and EDCI.HCl (110 mg, 0.57 mmol) were added at room temperature. After 2 minutes, piperazine-1-yl-(2-trifluoromethyl-phenyl)-methanone hydrochloride (85.2 mg, 0.29 mmol) was added. The resulting mixture was stirred at room temperature overnight. Water was then added, and the product was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. Purification by preparative HPLC (Column: Zorbax-XDB-9.4×250 mm, 5 μm, mobile phase: A, 0.1% Trifluoroacetic acid, B-Acetonitrile, Flow: 7 ml/min) afforded 68 mg (45% yield) of 2-(4-hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-acetamide as a white crystalline solid. LC-MS purity: 94.32%, HPLC purity: 98.38%. 1H NMR (DMSO): δ 9.4 (s, 1H,), 8.0 (t, 1H), 7.9-7.7 (m, 2H), 7.65 (t, 1H), 7.5 (d, 1H), 7.0 (d, 2H), 6.6 (d, 2H), 4.04-3.9 (d, 2H), 3.7-3.5 (m, 4H), 3.25 (m, 4H), 3.0 (m, 2H).

Aufarbeitung

  1. extractionthe product was extracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto afford the crude product
  6. customPurification by preparative HPLC (Column

Quellen und Nachweise

ORD-Eintrag
ord-3043987c371c42c88b81980ba43f28c1
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07842696B2

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