Water → 4-(3-(6-(trifluoromethyl)pyridin-3-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamide

HRID 1666435Notes

Reaction equation

HRID 1666435 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][C:5](=[CH:8][C:9]2[CH:10]=[C:11]([CH:23]=[CH:24][CH:25]=2)[O:12][C:13]2[CH:14]=[CH:15][C:16]([C:19]([F:22])([F:21])[F:20])=[N:17][CH:18]=2)[CH2:4][CH2:3]1.[N:26]1[CH:31]=[CH:30][CH:29]=[C:28]([NH:32][C:33](=O)[O:34]C2C=CC=CC=2)[N:27]=1.C(N(CC)CC)C.O>CS(C)=O>[F:21][C:19]([F:22])([F:20])[C:16]1[N:17]=[CH:18][C:13]([O:12][C:11]2[CH:10]=[C:9]([CH:25]=[CH:24][CH:23]=2)[CH:8]=[C:5]2[CH2:6][CH2:7][N:2]([C:33]([NH:32][C:28]3[N:27]=[N:26][CH:31]=[CH:30][CH:29]=3)=[O:34])[CH2:3][CH2:4]2)=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 20150036Phenyl pyridazin-3-ylcarbamateHCID 668761645-(3-(Piperidin-4-ylidenemethyl)phenoxy)-2-(trifluoromethyl)pyridine hydrochloride

Product 1

HCID 249651444-(3-(6-(trifluoromethyl)pyridin-3-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamideYield 72.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 5-(3-(piperidin-4-ylidenemethyl)phenoxy)-2-(trifluoromethyl)pyridine hydrochloride (0.100 g), phenyl pyridazin-3-ylcarbamate (0.070 g, 1.2 equiv), and triethylamine (0.083 mL, 2.2 equiv) in dimethyl sulfoxide (2 mL, 0.13 M) was heated to 65° C. for 2 h. The reaction was cooled to room temperature. Water was added and the mixture was extracted with ethyl acetate (3×). The combined organic extracts was washed with water and brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography (0-100% ethyl acetate/dichloromethane) to give the title compound as a white foam (0.089 g, 72% yield). 1H NMR (400 MHz, CDCl3) δ ppm 2.46 (2H, t, J=5.5 Hz), 2.56 (2H, t, J=5.6 Hz), 3.60 (2H, t, J=5.8 Hz), 3.69 (2H, t, J=5.8 Hz), 6.37 (1H, s), 6.92 (2H, m), 7.07 (1H, d, J=7.6 Hz), 7.30-7.46 (3H, m), 7.62 (1H, d, J=8.8 Hz), 8.25 (1H, d, J=8.2 Hz), 8.45 (1H, d, J=2.5 Hz), 8.76 (1H, d, J=1.9 Hz).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×)
  2. washThe combined organic extracts was washed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-4d2f89c1a6d54372ae7068717e179423
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

Loading…