1-Hydroxybenzotriazole → N-biphenyl-4-yl-3-oxo-3-(4-o-tolylamino-piperidin-1-yl)-propionamide

HRID 1093671Notes

Reaction equation

HRID 1093671 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.[NH:53]1[CH2:58][CH2:57][CH:56]([NH:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=2[CH3:66])[CH2:55][CH2:54]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](=[O:12])[N:53]2[CH2:58][CH2:57][CH:56]([NH:59][C:60]3[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=3[CH3:66])[CH2:55][CH2:54]2)=[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 66545677Piperidin-4-yl-o-tolyl-amine dihydrochloride

Product 1

HCID 57874392N-biphenyl-4-yl-3-oxo-3-(4-o-tolylamino-piperidin-1-yl)-propionamideYield 25%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of N-biphenyl-4-yl-malonamic acid (0.1 g, 0.00038 mole) in DMF (1 mL) was added DIPEA (0.245 g, 0.0019 mole), HOBt (0.056 g, 0.00042 mole) and EDCI.HCl (0.145 g, 0.00076 mole). After 2 minutes piperidin-4-yl-o-tolyl-amine dihydrochloride (0.106 g, 0.00042 mole) was added and the resulting mixture was stirred for 16 hours. 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 0.04 g (25%) of N-biphenyl-4-yl-3-oxo-3-(4-o-tolylamino-piperidin-1-yl)-propionamide. LC-MS purity: 428.23 (M+1)+, 93.11%, 1H NMR (DMSO-d6): δ 7.7 (m, 6H), 7.5 (t, 2H), 7.3 (t, 1H), 7.2 (q, 2H), 6.65 (q, 2H), 4.5 (d, 1H), 4.0 (d, 1H), 3.6 (m, 1H), 3.5 (s, 2H), 3.3 (s, 1H), 3.0 (t, 1H), 2.2 (m, 3H), 2.1 (s, 2H), 1.5 (t, 2H).

Workup

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

Sources & evidence

ORD record
ord-c24f35be6f9446368bda66474a728299
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

Loading…