Water → N-(Pyridin-3-yl)-4-(1-(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)ethylidene)piperidine-1-carboxamide

HRID 1666480Notes

Reaction equation

HRID 1666480 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH:7][C:8](=O)[O:9]C2C=CC=CC=2)[CH:2]=1.FC(F)(F)C(O)=O.[NH:24]1[CH2:29][CH2:28][C:27](=[C:30]([C:32]2[CH:33]=[C:34]([CH:46]=[CH:47][CH:48]=2)[O:35][C:36]2[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:38][N:37]=2)[CH3:31])[CH2:26][CH2:25]1.C(N(CC)CC)C.O>CS(C)=O>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH:7][C:8]([N:24]2[CH2:29][CH2:28][C:27](=[C:30]([C:32]3[CH:48]=[CH:47][CH:46]=[C:34]([O:35][C:36]4[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:43])[F:44])=[CH:38][N:37]=4)[CH:33]=3)[CH3:31])[CH2:26][CH2:25]2)=[O:9])[CH:2]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 6935890Phenyl pyridin-3-ylcarbamateHCID 866239122-(3-(1-(Piperidin-4-ylidene)ethyl)phenoxy)-5-(trifluoromethyl)pyridine trifluoroacetate

Product 1

HCID 24967638N-(Pyridin-3-yl)-4-(1-(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)ethylidene)piperidine-1-carboxamideYield 66.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of phenyl pyridin-3-ylcarbamate (120 mg, 0.562 mmol) in DMSO (5 mL) was added 2-(3-(1-(piperidin-4-ylidene)ethyl)phenoxy)-5-(trifluoromethyl)pyridine trifluoroacetate (260 mg, 0.516 mmol), followed by triethylamine (0.16 mL, 1.12 mmol). The reaction was stirred at 60° C. overnight. Water was added and the mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography (0-5% MeOH/CH2Cl2) to give the title compound (161 mg, 61% yield) as a clear oil which formed a foam under high vacuum. MS (APCI 10V) AP+ 469.18; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.99 (s, 3H) 2.31 (t, 2H) 2.50 (t, 2H) 3.40 (t, 2H) 3.61 (t, 2H) 6.63 (br. s., 1H) 6.89 (t, 1H) 6.97-7.04 (m, 3H) 7.17-7.22 (m, 1H) 7.37 (t, 1H) 7.89 (dd, 1H) 7.96 (dd, 1H) 8.23 (dd, 1H) 8.41 (dd, 2H).

Workup

  1. extractionthe mixture was extracted with EtOAc
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-aac26a3651604e7fa545b70b0e080c69
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

Loading…