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

HRID 1666417Notes

Reaction equation

HRID 1666417 reaction equation
[NH:1]1[CH2:6][CH2:5][C:4](=[CH:7][C:8]2[CH:9]=[C:10]([CH:24]=[CH:25][CH:26]=2)[O:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[CH:14][N:13]=2)[CH2:3][CH2:2]1.[N:27]1[CH:32]=[CH:31][CH:30]=[C:29]([NH:33][C:34](=O)[O:35]C2C=CC=CC=2)[N:28]=1.C(N(CC)CC)C>CS(C)=O.O>[F:22][C:20]([F:23])([F:21])[CH2:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([O:11][C:10]2[CH:9]=[C:8]([CH:26]=[CH:25][CH:24]=2)[CH:7]=[C:4]2[CH2:5][CH2:6][N:1]([C:34]([NH:33][C:29]3[N:28]=[N:27][CH:32]=[CH:31][CH:30]=3)=[O:35])[CH2:2][CH2:3]2)=[N:13][CH:14]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 20150036Phenyl pyridazin-3-ylcarbamateHCID 668761422-(3-(Piperidin-4-ylidenemethyl)phenoxy)-5-(2,2,2-trifluoroethoxy)pyridine

Product 1

HCID 249647874-(3-(5-(2,2,2-trifluoroethoxy)pyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamideYield 55%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of 2-(3-(piperidin-4-ylidenemethyl)phenoxy)-5-(2,2,2-trifluoroethoxy)pyridine (0.2 g, 0.54 mmol) in DMSO (3 mL) was added phenyl pyridazin-3-ylcarbamate (0.118 g, 0.54 mmol) followed by triethylamine (0.235 mL, 1.692 mmol). The resulting mixture was stirred at RT for 12 h. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (30% acetone, 70% hexane) to give the title compound (0.141 g, 55%). 1H NMR (500 MHz, CDCl3): δ 8.75 (s, 1H), 8.6 (s, 1H), 7.92 (d, J=2.6 Hz, 1H), 7.54 (s, 1H), 7.33 (m, 2H), 7.01 (d, J=7.5 Hz, 1H), 6.91 (m, 3H), 6.41 (s, 1H), 4.35 (q, J=8 Hz, 2H), 3.74 (m, 2H), 3.65 (m, 2H), 2.62 (m, 2H), 2.48 (m, 2H). 13C NMR (125 MHz, CDCl3): δ 158.95, 156.57, 154.55, 150.42, 138.82, 137.61, 134.35, 129.50, 128.19, 127.97, 125.07, 124.87, 124.15, 121.03, 118.80, 112.57, 67.60, 67.31, 67.03, 66.74, 45.65, 44.63, 35.75, 29.14; m/z (486.1, M+ H+); HPLC: 93.7%.

Workup

  1. extractionextracted with EtOAc
  2. extractionThe organic extract
  3. dry with materialwas dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (30% acetone, 70% hexane)

Sources & evidence

ORD record
ord-03ca029f562b4204aa747cbb3ef3c736
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

Loading…