2-Fluorobenzoic acid → N-{2-[4-(2-fluoro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-4-phenoxy-benzamide

HRID 1178031Notes

Reaction equation

HRID 1178031 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13]([OH:15])=O.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.[O:42]=[C:43]([N:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1)[CH2:44][NH:45][C:46](=[O:60])[C:47]1[CH:52]=[CH:51][C:50]([O:53][C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)=[CH:49][CH:48]=1>CN(C=O)C.O>[F:10][C:11]1[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13]([N:64]1[CH2:65][CH2:66][N:61]([C:43](=[O:42])[CH2:44][NH:45][C:46](=[O:60])[C:47]2[CH:48]=[CH:49][C:50]([O:53][C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=3)=[CH:51][CH:52]=2)[CH2:62][CH2:63]1)=[O:15]

Participants

8

Reactant 5

HCID 99352-Fluorobenzoic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66953134N-(2-Oxo-2-piperazin-1-yl-ethyl)-4-phenoxy-benzamide hydrochloride

Product 1

HCID 33466324N-{2-[4-(2-fluoro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-4-phenoxy-benzamideYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.106 mL, 0.62 mmol) was added drop wise to 2-fluorobenzoic acid (34 mg, 0.25 mmol) in DMF (5 mL). EDCI (98 mg, 0.51 mmol) and HOBT (33 mg, 0.25 mmol) were added consecutively and, after 10 mins, N-(2-Oxo-2-piperazin-1-yl-ethyl)-4-phenoxy-benzamide hydrochloride (77 mg, 0.25 mmol) was added and the resulting mixture was stirred at room temperature overnight. Water was then added, and the product was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. Purification using column chromatography (silica gel of mesh size of 60-120 using 70:30 EtOAc:hexane as eluent) afforded N-{2-[4-(2-fluoro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-4-phenoxy-benzamide in 42% yield. LC-MS purity: 97%, 1H NMR (DMSO-D6): δ 8.5 (t, 1H), 7.9 (d, 2H), 7.5 (m, 4H), 7.3 (m, 2H), 7.2 (t, 1H), 7.1 (m, 4H), 4.2 (dd, 2H), 3.6 (m, 4H), 3.5 (m, 2H), 3.2 (m, 2H).

Workup

  1. extractionthe product was extracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto afford the crude product
  6. customPurification

Sources & evidence

ORD record
ord-db8ae0e167884084809ca7a85841372b
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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