1-Hydroxybenzotriazole → N-biphenyl-4-yl-3-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-3-oxo-propionamide

HRID 1665594Notes

Reaction equation

HRID 1665594 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.[F:52][C:53]([F:70])([F:69])[C:54]1[CH:59]=[CH:58][C:57]([F:60])=[CH:56][C:55]=1[C:61]([N:63]1[CH2:68][CH2:67][NH:66][CH2:65][CH2:64]1)=[O:62]>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]([N:66]2[CH2:67][CH2:68][N:63]([C:61](=[O:62])[C:55]3[CH:56]=[C:57]([F:60])[CH:58]=[CH:59][C:54]=3[C:53]([F:70])([F:69])[F:52])[CH2:64][CH2:65]2)=[O:31])=[CH:24][CH:25]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 55049154N-biphenyl-4-yl-malonamic acidHCID 66625607(2-Trifluoromethyl-5-fluoro-phenyl)-piperazin-1-yl-methanone hydrochloride

Product 1

HCID 44230806N-biphenyl-4-yl-3-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-3-oxo-propionamideYield 38%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

HOBt (25 mg, 0.185 mmol) and DIPEA (22 mg, 0.175 mmol) were added to a stirred solution of N-biphenyl-4-yl-malonamic acid (50 mg, 0.175 mmol) in DMF (3 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (50 mg, 0.26 mmol) followed by (2-trifluoromethyl-5-fluoro-phenyl)-piperazin-1-yl-methanone hydrochloride (60 mg, 0.193 mmol) were added. The reaction mixture was stirred at room temperature overnight. Water was then added and the resulting precipitate was filtered. The solid was purified by column chromatography using silica gel 60-120 mesh and 40% ethyl acetate in hexane as eluant to afford 34 mg (38%) of N-biphenyl-4-yl-3-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-3-oxo-propionamide. LCMS: 514.17M+1)+, 95.5%. 1H NMR: (CDCl3): δ 9.6 (d, 1H), 7.75 (m, 1H), 7.6 (m, 6H), 7.44 (t, 2H), 7.35 (t, 1H), 7.2 (m, 1H), 7.06 (m, 1H), 4.0 (m, 2H), 3.7 (m, 4H), 3.56 (s, 2H), 3.48 (s, 1H), 3.26 (m, 3H).

Workup

  1. additionwere added
  2. filtrationthe resulting precipitate was filtered
  3. customThe solid was purified by column chromatography

Sources & evidence

ORD record
ord-f12fc23fb727432f9d6f4100d32eddb6
Source dataset
uspto-grants-2011_10
Patent number
US08039463B2

Reaction notes

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