1-Hydroxybenzotriazole → N-biphenyl-4-yl-3-oxo-3-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-propionamide

HRID 1665592Notes

Reaction equation

HRID 1665592 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[C:20]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:32])[CH2:28][C:29]([OH:31])=O)=[CH:22][CH:21]=1.CCN=C=NCCCN(C)C.Cl.Cl.[N:52]1([C:58]([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=2[C:66]([F:69])([F:68])[F:67])=[O:59])[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1>CN(C=O)C.O>[C:20]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:21]=[CH:22][C:23]([NH:26][C:27](=[O:32])[CH2:28][C:29](=[O:31])[N:55]2[CH2:56][CH2:57][N:52]([C:58](=[O:59])[C:60]3[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=3[C:66]([F:69])([F:67])[F:68])[CH2:53][CH2:54]2)=[CH:24][CH:25]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 167337831-(2-Trifluoromethylbenzoyl)piperazine hydrochlorideHCID 55049154N-biphenyl-4-yl-malonamic acid

Product 1

HCID 44219135N-biphenyl-4-yl-3-oxo-3-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-propionamideYield 30%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

HOBt (19 mg, 0.14 mmol) and DIPEA (0.017 mg, 0.14 mmol) were added to a stirred solution of N-biphenyl-4-yl-malonamic acid (40 mg, 0.14 mmol) in DMF (3 mL). The mixture was cooled to 10° C. and EDCI.HCl (40 mg, 0.2 mmol) followed by piperazin-1-yl-(2-trifluoromethyl-phenyl)-methanone hydrochloride (45 mg, 0.15 mmol) were added. The mixture was stirred at room temperature overnight, then diluted with water. The resulting precipitate was filtered and the residue was purified by column chromatography using silica gel 60-120 mesh and 90% ethyl acetate in hexane as eluant to afford 20 mg (30%) of N-biphenyl-4-yl-3-oxo-3-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-propionamide. LCMS: 496.18 (M+1)+, 97.3%. 1H NMR: (CDCl3): δ 9.6 (d, 1H), 7.76 (d, 1H), 7.6 (m, 7H), 7.44 (t, 2H), 7.35 (t, 2H), 4.0 (m, 2H), 3.7 (m, 4H), 3.5 (m, 4H), 3.25 (m, 2H).

Workup

  1. additionwere added
  2. filtrationThe resulting precipitate was filtered
  3. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-46ecf9da05c9462c8342a38a9f17610f
Source dataset
uspto-grants-2011_10
Patent number
US08039463B2

Reaction notes

Loading…