Dimethylformamide → 3-(4-Hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-propionamide

HRID 1178071

Reaction equation

HRID 1178071 reaction equation
CCN(C(C)C)C(C)C.[OH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][C:19]([NH:21][CH2:22][C:23]([OH:25])=O)=[O:20])=[CH:13][CH:12]=1.C1C=CC2N([OH:35])N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[N:49]1([C:55]([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=2[C:63]([F:66])([F:65])[F:64])=[O:56])[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1.CN([CH:70]=[O:71])C>O>[F:64][C:63]([F:66])([F:65])[C:70]([OH:71])=[O:35].[OH:10][C:11]1[CH:12]=[CH:13][C:14]([CH2:17][CH2:18][C:19]([NH:21][CH2:22][C:23](=[O:25])[N:52]2[CH2:53][CH2:54][N:49]([C:55](=[O:56])[C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=3[C:63]([F:66])([F:64])[F:65])[CH2:50][CH2:51]2)=[O:20])=[CH:15][CH:16]=1

Participants

9

Reactant 6

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 577651N-[(4-Hydroxybenzoyl)acetyl]glycineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 167337831-(2-Trifluoromethylbenzoyl)piperazine hydrochloride

Product 2

HCID 6422Trifluoroacetic acidYield 0.1%HCID 595596673-(4-Hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-propionamideYield 58.25%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

DIPEA (145 mg, 0.194 mL, 1.12 mmol) was added to a stirred solution of [3-(4-hydroxy-phenyl)propionylamino]-acetic acid (50 mg, 0.22 mmol) in DMF (4 mL). HOBT (33.3 mg, 0.25 mmol) and EDCI.HCl (107 mg, 0.56 mmol) were added at room temperature. After 2 minutes piperazine-1-yl-(2-trifluoromethyl-phenyl)-methanone hydrochloride (72.6 mg, 0.25 mmol) was added. The resulting mixture was stirred at room temperature for 24 hours. 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-Eclipse-XDB-C18-9.4×250 mm, 5 μm, mobile phase: A-0.1% Trifluoroacetic acid, B-Acetonitrile, Flow: 7 ml/min) afforded 60 mg (58.25% yield) of 3-(4-Hydroxy-phenyl) N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-propionamide as a pale white crystalline solid (60 mg). LC-MS purity: 91.16%, HPLC purity: 98.8%. 1H NMR (DMSO): δ 9.2 (s, 1H,), 8.0 (t, 1H), 7.92-7.8 (m, 2H), 7.7 (t, 1H), 7.56 (d, 1H), 7.0 (d, 2H), 6.66 (d, 2H), 4.08-3.94 (d, 2H), 3.84-3.68 (m, 2H), 3.66-3.5 (bs, 4H), 3.2-3.1 (bd, 2H), 2.7 (bs, 2H), 2.4 (t, 2H).

Workup

  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

Sources & evidence

ORD record
ord-3ee327f6e16e49deac7e31fee8edd8e8
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Linked notes

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