Triethylamine → 4-(3-cyclopropyl-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamide

HRID 1666467Notes

Reaction equation

HRID 1666467 reaction equation
[CH:1]1([C:4]2[CH:5]=[C:6]([CH:18]=[C:19]([CH:21]=[C:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[CH:20]=2)[O:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][N:9]=2)[CH2:3][CH2:2]1.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30]([NH:34][C:35](=[O:43])OC2C=CC=CC=2)C=1.C([N:46](CC)CC)C>CS(C)=O.O>[CH:1]1([C:4]2[CH:20]=[C:19]([CH:18]=[C:6]([O:7][C:8]3[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:15])[F:16])=[CH:10][N:9]=3)[CH:5]=2)[CH:21]=[C:22]2[CH2:23][CH2:24][N:25]([C:35]([NH:34][C:30]3[N:46]=[N:28][CH:33]=[CH:32][CH:31]=3)=[O:43])[CH2:26][CH2:27]2)[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 6935890Phenyl pyridin-3-ylcarbamateHCID 668754182-(3-Cyclopropyl-5-(piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine

Product 1

HCID 249679964-(3-cyclopropyl-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamideYield 66%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of 2-(3-cyclopropyl-5-(piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine (0.15 g, 0.401 mmol) and phenyl pyridin-3-ylcarbamate (85.8 mg, 0.4 mmol) in DMSO (1.5 mL) was added triethylamine (0.55 mL, 4.0 mmol) and the mixture was stirred overnight. The reaction mixture was diluted with water and extracted with ethyl acetate three times. The organic layer was washed with brine, dried over Na2SO4, and evaporated to dryness. The residue was purified by silica gel column chromatography (38% acetone in hexane) to give the title compound (0.13 g, 66%). 1H NMR (500 MHz, CDCl3): δ 8.77 (s, 1H), 8.45 (s, 1H), 8.41 (s, 1H), 7.89 (d, J=8.5 Hz, 1H), 7.47 (t, J=4.5 Hz, 1H), 6.99 (d, J=8.5 Hz, 1H), 6.81 (s, 1H), 6.77 (s, 1H), 6.70 (s, 1H), 6.38 (s, 1H), 3.70 (m, 2H), 3.60 (m, 2H), 2.60 (m, 2H), 2.47 (d, 2H), 1.87 (m, 1H), 0.98 (d, J=8 Hz, 2H), 0.70 (d, J=4.5 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ 165.83, 156.60, 153.17, 146.31, 145.54, 138.65, 137.71, 136.70, 128.20, 124.83, 123.63, 118.77, 116.75, 111.30, 45.64, 44.62, 35.73, 29.21, 15.44, 9.51; m/z (496.2, M+ H+); HPLC: 98.6%.

Workup

  1. extractionextracted with ethyl acetate three times
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. customevaporated to dryness
  5. customThe residue was purified by silica gel column chromatography (38% acetone in hexane)

Sources & evidence

ORD record
ord-e4b0309b35264d6fb87c826d34d5afa4
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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