1-Hydroxybenzotriazole → N-biphenyl-4-yl-3-[4-(2,3-dimethyl-phenylamino)-piperidin-1-yl]-3-oxo-propionamide

HRID 1093674Notes

Reaction equation

HRID 1093674 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.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.Cl.[CH3:53][C:54]1[C:59]([CH3:60])=[CH:58][CH:57]=[CH:56][C:55]=1[NH:61][CH:62]1[CH2:67][CH2:66][NH:65][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[CH2:66][CH2:67][CH:62]([NH:61][C:55]3[CH:56]=[CH:57][CH:58]=[C:59]([CH3:60])[C:54]=3[CH3:53])[CH2:63][CH2:64]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 66591674(2,3-Dimethyl-phenyl)-piperidin-4-yl-amine dihydrochloride

Product 1

HCID 57874417N-biphenyl-4-yl-3-[4-(2,3-dimethyl-phenylamino)-piperidin-1-yl]-3-oxo-propionamideYield 44%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of N-biphenyl-4-yl-malonamic acid (0.101 g, 0.00039 mole) in DMF (3 mL) was added DIPEA (0.233 g, 0.0018 mole), HOBt (0.053 g, 0.00039 mole) and EDCI.HCl (0.138 g, 0.00072 mole). After 2 minutes (2,3-dimethyl-phenyl)-piperidin-4-yl-amine dihydrochloride (0.1 g, 0.00036 mole) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the resulting precipitate was isolated by filtration. Purification by column chromatography using silica gel 60-120 mesh (1% methanol in chloroform) afforded 0.07 g (44%) of N-biphenyl-4-yl-3-[4-(2,3-dimethyl-phenylamino)-piperidin-1-yl]-3-oxo-propionamide. LC-MS purity: 442.24 (M+1)+, 95.5%, 1H NMR (DMSO-d6): δ 10.2 (s, 1H), 7.7 (m, 6H), 7.6 (t, 2H), 7.4 (d, 1H), 6.8 (t, 1H), 6.5 (d, 1H), 6.4 (d, 1H), 4.4 (t, 2H), 4.0 (d, 1H), 3.6 (bs, 3H), 3.2 (t, 1H), 2.8 (t, 1H), 2.2 (s, 3H), 2.0 (bs, 5H), 1.5 (d, 1H), 1.4 (d, 1H).

Workup

  1. customthe resulting precipitate was isolated by filtration
  2. customPurification by column chromatography

Sources & evidence

ORD record
ord-b97c176d046146dab76edfabcd1fd0e1
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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