1-Hydroxybenzotriazole → N-{2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-6-phenylamino-nicotinamide

HRID 1093657Notes

Reaction equation

HRID 1093657 reaction equation
[C:1]1([NH:7][C:8]2[N:13]=[CH:12][C:11]([C:14]([NH:16][CH2:17][C:18]([OH:20])=O)=[O:15])=[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.[Cl:53][C:54]1[CH:66]=[CH:65][CH:64]=[CH:63][C:55]=1[O:56][CH:57]1[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]1>CN(C=O)C.O>[Cl:53][C:54]1[CH:66]=[CH:65][CH:64]=[CH:63][C:55]=1[O:56][CH:57]1[CH2:62][CH2:61][N:60]([C:18](=[O:20])[CH2:17][NH:16][C:14](=[O:15])[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)=[N:13][CH:12]=2)[CH2:59][CH2:58]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 167325894-(2-Chlorophenoxy)piperidine hydrochlorideHCID 57874437[(6-Phenylamino-pyridine-3-carbonyl)-amino]-acetic acid

Product 1

HCID 44233263N-{2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-6-phenylamino-nicotinamideYield 62%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of [(6-phenylamino-pyridine-3-carbonyl)-amino]-acetic acid (0.035 g, 0.00013 mol) in DMF (1 mL) was added DIPEA (0.05 g, 0.00039 mol), HOBt (0.0209 g, 0.00015 mol) and EDCI.HCl (0.029 g, 0.0001549 mol) at ambient temperature. After 2 minutes 4-(2-chloro-phenoxy)-piperidine hydrochloride (0.0382 g, 0.00015 mol) 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 was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography using silica gel 60-120 mesh (70% ethyl acetate in hexane) to afford 0.037 g (62%) of N-{2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-6-phenylamino-nicotinamide. LCMS: 465.16 (M+1)+, 96.6%, 1H NMR (DMSO-d6): δ 9.4 (s, 1H), 8.8 (s, 1H), 8.4 (t, 1H), 8.0 (dd, 1H), 7.7 (d, 2H), 7.45 (d, 1H), 7.4 (m, 4H), 7.0 (d, 2H), 6.8 (d, 1H), 4.7 (m, 1H), 4.25 (m, 2H), 3.7 (m, 2H), 3.5 (m, 2H), 2.0 (m, 2H), 1.7 (q, 2H).

Workup

  1. extractionthe product was extracted with ethyl acetate
  2. washThe ethyl acetate was washed with brine solution
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-9245217ea5514f97a0b8a18446a366cd
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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