Phosphorus oxychloride → N-benzyl-3-(4-chloro-5-cyano-6-(4-phenoxyphenyl)pyridin-2-yl)piperidine-1-carboxamide

HRID 81059Notes

Reaction equation

HRID 81059 reaction equation
[CH2:1]([NH:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[NH:18][C:19]([C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[CH:28][CH:27]=3)=[C:20]([C:24]#[N:25])[C:21](=O)[CH:22]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:41])=O>CN(C)C=O>[CH2:1]([NH:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[CH:22]=[C:21]([Cl:41])[C:20]([C:24]#[N:25])=[C:19]([C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[CH:28][CH:27]=3)[N:18]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 66927068N-benzyl-3-(5-cyano-4-oxo-6-(4-phenoxyphenyl)-1,4-dihydropyridin-2-yl)piperidine-1-carboxamide

Product 1

HCID 66927015N-benzyl-3-(4-chloro-5-cyano-6-(4-phenoxyphenyl)pyridin-2-yl)piperidine-1-carboxamideYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of N-benzyl-3-(5-cyano-4-oxo-6-(4-phenoxyphenyl)-1,4-dihydropyridin-2-yl)piperidine-1-carboxamide (167.9 mg, 0.333 mmol) and phosphorus oxychloride (0.093 mL, 0.998 mmol) in N,N-dimethylformamide (1 mL) was heated to 90° C. in a sealed tube for 50 min. The mixture was concentrated. The residue was dissolved in dichloromethane, washed with saturated sodium bicarbonate and concentrated. Silica gel chromatography, eluting with 0-50% ethyl acetate in hexanes, gave N-benzyl-3-(4-chloro-5-cyano-6-(4-phenoxyphenyl)pyridin-2-yl)piperidine-1-carboxamide as white solid (144.4 mg, 83% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.92 (2H, δ, J=8.53 Hz), 7.28-7.46 (8H, m), 7.19 (1H, t, J=7.40 Hz), 7.06-7.14 (4H, m), 5.15 (2H, s), 4.36 (1H, hr. s), 4.12-4.25 (1H, m), 3.16 (1H, br. s), 2.92 (2H, br. s), 2.07 (1H, br. s), 1.84 (2H, hr. s), 1.58-1.70 (1H, m); MS (ES+) m/z: 524 (M+H); LC retention time: 4.330 min (analytical HPLC Method A).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionThe residue was dissolved in dichloromethane
  3. washwashed with saturated sodium bicarbonate
  4. concentrationconcentrated
  5. washSilica gel chromatography, eluting with 0-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-08c77e60429f4d6bb8452c4c0f6514fb
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

Loading…