1-Hydroxybenzotriazole → Biphenyl-4-carboxylicacid {2-oxo-2-[4-(3,4,5-trifluoro-benzoyl)-piperazin-1-yl]-ethyl}-amide

HRID 1178092Notes

Reaction equation

HRID 1178092 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:12]=[C:13]([CH:17]=[C:18]([F:21])[C:19]=1[F:20])[C:14]([OH:16])=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[O:44]=[C:45]([N:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1)[CH2:46][NH:47][C:48]([C:50]1[CH:55]=[CH:54][C:53]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)=[CH:52][CH:51]=1)=[O:49]>CN(C=O)C.O>[O:44]=[C:45]([N:62]1[CH2:67][CH2:66][N:65]([C:14](=[O:16])[C:13]2[CH:17]=[C:18]([F:21])[C:19]([F:20])=[C:11]([F:10])[CH:12]=2)[CH2:64][CH2:63]1)[CH2:46][NH:47][C:48]([C:50]1[CH:51]=[CH:52][C:53]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)=[CH:54][CH:55]=1)=[O:49]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 8531543,4,5-Trifluorobenzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57855677Biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide

Product 1

HCID 57855644Biphenyl-4-carboxylicacid {2-oxo-2-[4-(3,4,5-trifluoro-benzoyl)-piperazin-1-yl]-ethyl}-amideYield 25.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (149.8 mg, 1.15 mmol) was added to a stirred solution of 3,4,5-trifluoro-benzoic acid (45.3 mg, 0.26 mmol) in DMF (3 mL), HOBt (38.2 mg, 0.28 mmol) and EDCI.HCl (123.4 mg, 0.64 mmol) at room temperature. After 2 minutes biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide (100 mg, 0.31 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added, and the resulting precipitate was filtered. The residue was purified by column chromatography (using 60-120 mesh silica gel and 60% EtOAc in hexane as eluent) to afford 32 mg (25.8% yield) of biphenyl-4-carboxylicacid {2-oxo-2-[4-(3,4,5-trifluoro-benzoyl)-piperazin-1-yl]-ethyl}-amide, LC-MS purity: 98.04%, 1H NMR: (DMSO) δ 8.76-8.6 (bs, 1H), 8.08-7.92 (m, 2H), 7.88-7.72 (m, 4H), 7.6-7.4 (m, 4H), 4.2 (s, 2H), 3.6 (s, 5H), 3.2 (m, 3H).

Workup

  1. filtrationthe resulting precipitate was filtered
  2. customThe residue was purified by column chromatography (using 60-120 mesh silica gel and 60% EtOAc in hexane as eluent)

Sources & evidence

ORD record
ord-e27e79556ab947c69ae5e0d0cae8fc39
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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