1-Hydroxybenzotriazole → N-(2-{4-[methyl-(2-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-4-phenylamino-benzamide

HRID 1093595Notes

Reaction equation

HRID 1093595 reaction equation
[C:1]1([NH:7][C:8]2[CH:20]=[CH:19][C:11]([C:12]([NH:14][CH2:15][C:16]([OH:18])=O)=[O:13])=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[CH3:53][N:54]([CH:65]1[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=1[C:61]([F:64])([F:63])[F:62]>CN(C=O)C.O>[CH3:53][N:54]([C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=1[C:61]([F:64])([F:62])[F:63])[CH:65]1[CH2:70][CH2:69][N:68]([C:16](=[O:18])[CH2:15][NH:14][C:12](=[O:13])[C:11]2[CH:10]=[CH:9][C:8]([NH:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:20][CH:19]=2)[CH2:67][CH2:66]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57874498(4-Phenylamino-benzoylamino)-acetic acidHCID 66591695N-Methyl-N-(2-(trifluoromethyl)phenyl)piperidin-4-amine hydrochloride

Product 1

HCID 44235734N-(2-{4-[methyl-(2-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-4-phenylamino-benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (4-phenylamino-benzoylamino)-acetic acid (0.051 g, 0.00019 mol) in DMF (5 mL) was added DIPEA (0.061 g, 0.00048 mol), HOBt (0.025 g, 0.00019 mol) and EDCI.HCl (0.076 g, 0.00040 mol) at ambient temperature. After 2 minutes methyl-piperidin-4-yl-(2-trifluoromethyl-phenyl)-amine hydrochloride (0.047 g, 0.00016 mol) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by preparative HPLC [(column-Zorbax SB C18-21.2×150 mm, mobile phase-0.1% TFA in water (A)/Acetonitrile (B), gradient: (Time): (% B)-0:30; 2:50; 8:80)]) to afford 0.031 (38%) of N-(2-{4-[methyl-(2-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-4-phenylamino-benzamide. LCMS: 511.22 (M+1)+, 99.08%, 1H NMR (DMSO-d6): δ 8.6 (s, 1H), 8.2 (t, 1H), 7.8 (d, 2H), 7.7 (m, 3H), 7.4 (m, 3H), 7.2 (d, 2H), 7.1 (d, 2H), 6.9 (t, 1H), 4.4 (d, 1H), 4.1 (d, 2H), 3.9 (d, 1H), 3.1 (m, 3H), 2.6 (s, 4H), 1.8 (d, 2H), 1.4 (m, 1H).

Workup

  1. extractionthe product was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with brine solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by preparative HPLC [(column-Zorbax SB C18-21.2×150 mm, mobile phase-0.1% TFA in water (A)/Acetonitrile (B)

Sources & evidence

ORD record
ord-f91220b5bc18411c9cd3c01a11fa1e8e
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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