1-Hydroxybenzotriazole → N-Biphenyl-4-yl-3-oxo-3-[4-(3,4,5-trifluoro-benzoyl)-piperazin-1-yl]-propionamide

HRID 1665601Notes

Reaction equation

C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[F:20][C:21]1[CH:22]=[C:23]([CH:27]=[C:28]([F:31])[C:29]=1[F:30])[C:24]([OH:26])=O.CCN=C=NCCCN(C)C.Cl.Cl.[C:45]1([C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[CH:50]=[CH:49][C:48]([NH:51][C:52](=[O:62])[CH2:53][C:54](=[O:61])[N:55]2[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]2)=[CH:47][CH:46]=1>CN(C=O)C.O>[C:45]1([C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[CH:46]=[CH:47][C:48]([NH:51][C:52](=[O:62])[CH2:53][C:54](=[O:61])[N:55]2[CH2:56][CH2:57][N:58]([C:24](=[O:26])[C:23]3[CH:27]=[C:28]([F:31])[C:29]([F:30])=[C:21]([F:20])[CH:22]=3)[CH2:59][CH2:60]2)=[CH:49][CH:50]=1

Participants

Conditions

Temperature: 10 °C

Procedure

HOBt (34 mg, 0.25 mmol) and DIPEA (67.9 mg, 0.51 mmol) were added to a stirred solution of 3,4,5-trifluorobenzoic acid (37 mg, 0.21 mmol) in DMF (2 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (48 mg, 0.25 mmol) followed by N-biphenyl-4-yl-3-oxo-3-piperazin-1-yl-propionamide hydrochloride (75 mg, 0.2 mmol) were added. The reaction mixture was stirred at room temperature overnight then diluted with water. The resulting precipitate was filtered and purified by column chromatography using silica gel 60-120 mesh (40% ethyl acetate in hexane) to afford 42 mg (42%) of N-Biphenyl-4-yl-3-oxo-3-[4-(3,4,5-trifluoro-benzoyl)-piperazin-1-yl]-propionamide. LCMS: 482.16 (M+1)+ 94.2%, 1H NMR: (CDCl3): δ 9.5 (s, 1H), 7.58 (m, 6H), 7.43 (t, 2H), 7.34 (m, 1H), 7.08 (t, 2H), 3.7 (bs, 8H), 3.54 (s, 2H).

Workup

additionwere added
filtrationThe resulting precipitate was filtered
custompurified by column chromatography

Sources & evidence

ORD record: ord-5d802727d5a049ffabbb331bfcdc6970
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08039463B2

Reaction notes

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