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

HRID 1093677Notes

Reaction equation

HRID 1093677 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.[C:53]([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=1[NH:63][CH:64]1[CH2:69][CH2:68][NH:67][CH2:66][CH2:65]1)([CH3:56])([CH3:55])[CH3:54]>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:67]2[CH2:68][CH2:69][CH:64]([NH:63][C:58]3[CH:59]=[CH:60][CH:61]=[CH:62][C:57]=3[C:53]([CH3:56])([CH3:55])[CH3:54])[CH2:65][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 66591489(2-Tert-butyl-phenyl)-piperidin-4-yl-amine dihydrochloride

Product 1

HCID 57874422N-biphenyl-4-yl-3-[4-(2-tert-butyl-phenylamino)-piperidin-1-yl]-3-oxo-propionamideYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of N-biphenyl-4-yl-malonamic acid (0.091 g, 0.00036 mole) in DMF (1 mL) was added DIPEA (0.211 g, 0.0016 mole), HOBt (0.048 g, 0.00036 mole) and EDCI.HCl (0.125 g, 0.00065 mole). After 2 minutes (2-tert-butyl-phenyl)-piperidin-4-yl-amine dihydrochloride (0.1 g, 0.00033 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 0.062 g (40%) of N-biphenyl-4-yl-3-[4-(2-tert-butyl-phenylamino)-piperidin-1-yl]-3-oxo-propionamide. LC-MS purity: 470.27 (M+1)+, 96.38%, 1H NMR (DMSO-d6): δ 7.8-7.6 (m, 6H), 7.5 (t, 2H), 7.3 (d, 1H), 7.1 (d, 1H), 7.0 (t, 1H), 6.8 (d, 1H), 6.6 (t, 1H), 4.3 (d, 1H), 3.9 (d, 2H), 3.7 (s, 1H), 3.6 (s, 2H), 3.2 (t, 1H), 2.9 (t, 1H), 2.0 (t, 2H), 1.5 (t, 1H), 1.4 (s, 9H).

Workup

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

Sources & evidence

ORD record
ord-6138e41d16344bfd84ed0c0fd74c784e
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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