1-Hydroxybenzotriazole → 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-N-[4-(2-oxo-2H-pyridin-1-yl)-phenyl]-propionamide

HRID 1665662Notes

Reaction equation

C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[O:20]=[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]1[C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34](=[O:39])[CH2:35][C:36]([OH:38])=O)=[CH:29][CH:28]=1.CCN=C=NCCCN(C)C.Cl.Cl.[Br:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[C:60]([N:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1)=[O:61]>CN(C=O)C.O>[Br:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[C:60]([N:62]1[CH2:63][CH2:64][N:65]([C:36](=[O:38])[CH2:35][C:34]([NH:33][C:30]2[CH:29]=[CH:28][C:27]([N:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]3=[O:20])=[CH:32][CH:31]=2)=[O:39])[CH2:66][CH2:67]1)=[O:61]

Participants

Conditions

Temperature: 0 °C

Procedure

HOBt (75 mg, 0.55 mmol) and DIPEA (213 mg, 1.65 mmol) were added to a stirred solution of N-[4-(2-oxo-2H-pyridin-1-yl)-phenyl]-malonamic acid (150 mg, 0.55 mmol) in DMF (2.0 mL). The reaction mixture was cooled to 0° C. and EDCI.HCl (126 mg, 0.66 mmol) followed by (2-bromo-phenyl)-piperazin-1-yl-methanone hydrochloride (185 mg, 0.6 mmol) were added. The reaction mixture was stirred at room temperature overnight then diluted with water. The resulting precipitate was recrystallized from ethyl acetate:hexane (1:1) to afford 180 mg (21%) of 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-N-[4-(2-oxo-2H-pyridin-1-yl)-phenyl]-propionamide. LCMS: 524.09 (M+1)+9.7%, 1H NMR: (DMSO-d6): δ 7.7-7.2 (m, 8H), 6.5 (m, 1H), 6.3 (m, 1H), 3.8-3.6 (m, 5H), 3.6-3.34 (m, 3H), 3.2 (m, 2H).

Workup

additionwere added
customThe resulting precipitate was recrystallized from ethyl acetate:hexane (1:1)

Sources & evidence

ORD record: ord-7af101256edd47cb93d99a17444034ad
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08039463B2

Reaction notes

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