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

HRID 1666416Notes

Reaction equation

HRID 1666416 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)[CH: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[CH: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 6935890Phenyl pyridin-3-ylcarbamateHCID 668761422-(3-(Piperidin-4-ylidenemethyl)phenoxy)-5-(2,2,2-trifluoroethoxy)pyridine

Product 1

HCID 249647864-(3-(5-(2,2,2-trifluoroethoxy)pyridin-2-yloxy)benzylidene)-N-(pyridin-3-yl)piperidine-1-carboxamideYield 70.6%

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 (0.14 g, 0.38 mmol) in DMSO (3 mL) was added phenyl pyridin-3-ylcarbamate (0.082 g, 0.38 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 (0.13 g, 70%). 1H NMR (500 MHz, CDCl3): δ 8.74 (s, 1H), 8.30 (d, J=7.2 Hz, 1H), 8.22 (d, J=4.4 Hz, 1H), 7.91 (d, J=8.2 Hz, 1H), 7.32 (m, 4H), 7.02 (d, J=7.5 Hz, 1H), 6.95 (d, J=9 Hz, 1H), 6.95 (s, 1H), 6.90 (d, J=8.8 Hz, 1H), 6.39 (s, 1H), 4.33 (q, J=7.8 Hz, 2H), 3.65 (m, 2H), 3.55 (m, 2H), 2.60 (m, 2H), 2.47 (m, 2H). 13C NMR (125 MHz, CDCl3): δ 158.96, 154.56, 154.45, 150.43, 143.12, 140.48, 138.89, 137.80, 136.56, 134.41, 129.49, 127.96, 125.08, 124.74, 123.80, 121.02, 118.77, 112.57, 67.33, 67.05, 45.75, 44.70, 35.74, 29.16; m/z (485.1, M+ H+); HPLC: 93.6%.

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-81b67fce178b439d9d0dea78e55927ce
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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