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

HRID 1665602Notes

Reaction equation

HRID 1665602 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[Cl:20][C:21]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:22]=1[C:23]([OH:25])=O.CCN=C=NCCCN(C)C.Cl.Cl.[C:47]1([C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)[CH:52]=[CH:51][C:50]([NH:53][C:54](=[O:64])[CH2:55][C:56](=[O:63])[N:57]2[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]2)=[CH:49][CH:48]=1>CN(C=O)C.O>[C:47]1([C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)[CH:48]=[CH:49][C:50]([NH:53][C:54](=[O:64])[CH2:55][C:56]([N:57]2[CH2:58][CH2:59][N:60]([C:23](=[O:25])[C:22]3[CH:26]=[C:27]([C:30]([F:33])([F:32])[F:31])[CH:28]=[CH:29][C:21]=3[Cl:20])[CH2:61][CH2:62]2)=[O:63])=[CH:51][CH:52]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 6881822-Chloro-5-(trifluoromethyl)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66625265N-Biphenyl-4-yl-3-oxo-3-piperazin-1-yl-propionamide hydrochloride

Product 1

HCID 44230950N-biphenyl-4-yl-3-[4-(2-chloro-5-trifluoromethyl-benzoyl)-piperazin-1-yl]-3-oxo-propionamideYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

HOBt (34 mg, 0.25 mmol) and DIPEA (67.9 mg, 0.51 mmol) were added to a stirred solution of 2-chloro-5-trifluoromethylbenzoic acid (48 mg, 0.21 mmol) in DMF (3 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (48 mg, 0.25 mmol) followed by N-biphenyl-4-yl-3-oxo-3-piperazin-1-yl-propionamide hydrochloride (75 mg, 0.2 mmol) were added. The reaction mixture was stirred at room temperature overnight then diluted with water and extracted with ethyl acetate. The ethyl acetate was washed with brine solution, dried over Na2SO4 and evaporated. The residue was purified by column chromatography using silica gel 60-120 mesh (60% ethyl acetate in hexane) to afford 53 mg (48%) of N-biphenyl-4-yl-3-[4-(2-chloro-5-trifluoromethyl-benzoyl)-piperazin-1-yl]-3-oxo-propionamide. LCMS: 530.14 (M+1)+ 98.5%, 1H NMR: (CDCl3): δ 9.6 (d, 1H), 7.6 (m, 8H), 7.43 (t, 2H), 7.33 (t, 1H), 4.0 (m, 2H), 3.7 (m, 4H), 3.5 (d, 2H), 3.3 (m, 2H).

Workup

  1. additionwere added
  2. extractionextracted with ethyl acetate
  3. washThe ethyl acetate was washed with brine solution
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-953e2f4f1473481c94fb99ef08655a08
Source dataset
uspto-grants-2011_10
Patent number
US08039463B2

Reaction notes

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