1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-{2-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-4-(4-methyl-piperazin-1-yl)-benzamide

HRID 1177936Notes

Reaction equation

HRID 1177936 reaction equation
CCN(C(C)C)C(C)C.Cl.[CH3:11][N:12]1[CH2:17][CH2:16][N:15]([C:18]2[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][CH:19]=2)[CH2:14][CH2:13]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:49][CH2:50][C:51]([N:53]1[CH2:58][CH2:57][N:56]([C:59](=[O:71])[C:60]2[CH:65]=[C:64]([F:66])[CH:63]=[CH:62][C:61]=2[C:67]([F:70])([F:69])[F:68])[CH2:55][CH2:54]1)=[O:52]>CN(C=O)C.O>[F:66][C:64]1[CH:63]=[CH:62][C:61]([C:67]([F:69])([F:68])[F:70])=[C:60]([CH:65]=1)[C:59]([N:56]1[CH2:57][CH2:58][N:53]([C:51](=[O:52])[CH2:50][NH:49][C:22](=[O:24])[C:21]2[CH:20]=[CH:19][C:18]([N:15]3[CH2:14][CH2:13][N:12]([CH3:11])[CH2:17][CH2:16]3)=[CH:26][CH:25]=2)[CH2:54][CH2:55]1)=[O:71]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 185622734-(4-Methylpiperazin-1-yl)benzoic acid hydrochlorideHCID 669531292-Amino-1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]ethanone hydrochloride

Product 1

HCID 57855654N-{2-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-4-(4-methyl-piperazin-1-yl)-benzamideYield 41.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (350 mg, 0.5 mL, 2.7 mmol) was added to a stirred solution of 4-(4-methyl-piperazin-1-yl)-benzoic acid hydrochloride salt (116 mg, 0.45 mmol) in DMF (5 mL). HOBT (67 mg, 0.5 mmol) and EDCI (216 mg, 1.12 mmol) were then added at room temperature. After 2 minutes, 2-amino-1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride salt (184 mg, 0.5 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and filtered the solid residue. The obtained residue was purified by preparative HPLC to afford 100 mg (41.3% yield) N-{2-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-4-(4-methyl-piperazin-1-yl)-benzamide. LCMS Purity: 88.3%. 1H NMR (DMSO-d6): δ 10.4 (s, 1H), 8.4 (s, 1H), 8.0 (t, 1H), 7.86 (d, 2H), 7.64 (m, 2H), 7.1 (d, 2H), 4.2-3.96 (m, 4H), 3.66-3.4 (m, 8H), 3.24-3.0 (m, 6H), 2.9 (s, 3H).

Workup

  1. filtrationfiltered the solid residue
  2. customThe obtained residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-0763eb59b97b4e59bbd249d333ab346b
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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