1-Hydroxybenzotriazole → HCID 57855679, compound

HRID 1178099Notes

Reaction equation

HRID 1178099 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:12]=1[C:13]([OH:15])=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[O:43]=[C:44]([N:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1)[CH2:45][NH:46][C:47]([C:49]1[CH:54]=[CH:53][C:52]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)=[CH:51][CH:50]=1)=[O:48]>CN(C=O)C.O>[F:10][C:11]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:12]=1[C:13]([N:64]1[CH2:63][CH2:62][N:61]([C:44](=[O:43])[CH2:45][NH:46][C:47]([C:49]2[CH:54]=[CH:53][C:52]([C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)=[CH:51][CH:50]=2)=[O:48])[CH2:66][CH2:65]1)=[O:15]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 763392,5-Difluorobenzoic acidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57855677Biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide

Product 1

HCID 57855679HCID 57855679, compoundYield 46.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (149.8 mg, 1.15 mmol) was added to a stirred solution of 2,5-difluoro-benzoic acid (40.7 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 50% EtOAc in hexane as eluent) to afford 56 mg (46.9% yield) of biphenyl-4-carboxylicacid {2-[4-(2,5-difluoro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide, LC-MS purity: 97.42%, 1H NMR: (CDCl3) δ 7.98-7.88 (d, 2H), 7.74-7.58 (dd, 4H), 7.54-7.34 (m, 3H), 7.2-7.08 (s, 3H), 4.4-4.26 (d, 2H), 3.94-3.78 (m, 3H), 3.76-3.56 (d, 3H), 3.54-3.38 (d, 3H).

Workup

  1. filtrationthe resulting precipitate was filtered
  2. customThe residue was purified by column chromatography (using 60-120 mesh silica gel and 50% EtOAc in hexane as eluent)

Sources & evidence

ORD record
ord-0d6747d7fcda40caba18e818e89f0fd5
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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