1-Hydroxybenzotriazole → N-biphenyl-4-yl-3-[4-(2-bromo-phenoxy)-piperidin-1-yl]-3-oxo-propionamide

HRID 1093667Notes

Reaction equation

HRID 1093667 reaction equation
[C:1]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=[CH:5][C:4]([NH:7][C:8](=[O:13])[CH2:9][C:10]([OH:12])=O)=[CH:3][CH:2]=1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl.FC(F)(F)C(O)=O.[Br:58][C:59]1[CH:72]=[CH:71][CH:70]=[CH:69][C:60]=1[O:61][CH:62]1[CH2:67][CH2:66][N:65](N)[CH2:64][CH2:63]1>CN(C=O)C.O>[C:1]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:2]=[CH:3][C:4]([NH:7][C:8](=[O:13])[CH2:9][C:10]([N:65]2[CH2:64][CH2:63][CH:62]([O:61][C:60]3[CH:69]=[CH:70][CH:71]=[CH:72][C:59]=3[Br:58])[CH2:67][CH2:66]2)=[O:12])=[CH:5][CH:6]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 55049154N-biphenyl-4-yl-malonamic acidHCID 665919464-(2-Bromo-phenoxy)-piperidin-1-ylamine trifluoroacetate

Product 1

HCID 57874382N-biphenyl-4-yl-3-[4-(2-bromo-phenoxy)-piperidin-1-yl]-3-oxo-propionamideYield 31.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

To a stirred solution of N-biphenyl-4-yl-malonamic acid (0.075 g, 0.00029 mole) in DMF (2.0 mL) was added HOBt (0.042 g, 0.00031 mole) and DIPEA (0.083 g, 0.00065 mole). The mixture was cooled to 10° C. and EDCI.HCl (0.060 g, 0.00031 mole) followed by 4-(2-bromo-phenoxy)-piperidin-1-ylamine trifluoroacetate (0.106 g, 0.00029 mole) were added. The mixture was stirred at the ambient temperature overnight. The mixture was then diluted with water and the product was extracted with ethyl acetate. The organic layer was washed with brine and concentrated. The resulting residue was purified by column chromatography using silica gel 60-120 mesh (40% ethyl acetate in hexane) to afford 0.045 g (31%) of N-biphenyl-4-yl-3-[4-(2-bromo-phenoxy)-piperidin-1-yl]-3-oxo-propionamide. LCMS: 493 (M+1)+, 94.19%, 1H NMR (CDCl3): δ 10.0 (s, 1H), 7.66 (d, 2H), 7.58 (m, 5H), 7.44 (t, 2H), 7.32 (m, 1H), 6.9 (m, 2H), 4.52 (m, 1H), 4.15 (m, 1H), 3.56 (m, 1H), 3.54 (m, 2H), 3.51 (d, 2H), 2.0 (m, 2H), 1.8 (m, 2H).

Workup

  1. additionwere added
  2. extractionthe product was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. concentrationconcentrated
  5. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-7b6dc942c1ae4241b206840d1b4dde8b
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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