1-Hydroxybenzotriazole → HCID 57855672, compound

HRID 1178097Notes

Reaction equation

HRID 1178097 reaction equation
CCN(C(C)C)C(C)C.[Cl:10][C:11]1[C:19]([F:20])=[CH:18][C:14]([C:15]([OH:17])=O)=[C:13]([F:21])[CH:12]=1.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>[Cl:10][C:11]1[C:19]([F:20])=[CH:18][C:14]([C:15]([N:65]2[CH2:64][CH2:63][N:62]([C:45](=[O:44])[CH2:46][NH:47][C:48]([C:50]3[CH:55]=[CH:54][C:53]([C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=4)=[CH:52][CH:51]=3)=[O:49])[CH2:67][CH2:66]2)=[O:17])=[C:13]([F:21])[CH:12]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27332744-Chloro-2,5-difluorobenzoic acidHCID 57855677Biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide

Product 1

HCID 57855672HCID 57855672, compoundYield 50.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (149.8 mg, 1.15 mmol) was added to a stirred solution of 4-chloro-2,5-difluoro-benzoic acid (49.6 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 65 mg (50.7% yield) of biphenyl-4-carboxylicacid {2-[4-(4-chloro-2,5-difluoro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide, LC-MS purity: 99.40%, 1H NMR: (DMSO) δ 8.7-8.6 (s, 1H), 8.04-7.92 (d, 2H), 7.88-7.7 (q, 5H), 7.7-7.6 (s, 1H), 7.58-7.46 (d, 2H), 7.46-7.38 (d, 1H), 4.3-4.12 (d, 2H), 3.8-3.58 (d, 5H), 3.56-3.44 (s, 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-ff76451ac06b44c784bc1e8ff7dc1a88
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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