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

HRID 1666474Notes

Reaction equation

HRID 1666474 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([CH:19]=[C:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[CH:18]=1)[O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][N:7]=1.[N:26]1[CH:31]=[CH:30][CH:29]=[C:28]([NH:32][C:33](=O)[O:34]C2C=CC=CC=2)[CH:27]=1.C(N(CC)CC)C>CS(C)=O.O>[F:1][C:2]1[CH:18]=[C:17]([CH:16]=[C:4]([O:5][C:6]2[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][N:7]=2)[CH:3]=1)[CH:19]=[C:20]1[CH2:25][CH2:24][N:23]([C:33]([NH:32][C:28]2[CH:27]=[N:26][CH:31]=[CH:30][CH:29]=2)=[O:34])[CH2:22][CH2:21]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 6935890Phenyl pyridin-3-ylcarbamateHCID 668759742-(3-Fluoro-5-(piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine

Product 1

HCID 249676404-(3-fluoro-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylidene)-N-(pyridin-3-yl)piperidine-1-carboxamideYield 80%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

2-(3-Fluoro-5-(piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine (469 mg, 1.33 mmol) and phenyl pyridin-3-ylcarbamate (273 mg, 1.33 mmol) were dissolved in DMSO (4 mL) and triethylamine (0.53 mL, 3.83 mmol) was added. The reaction 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 (35% acetone in hexane) to give the title compound (500 mg, 80%). 1H NMR (500 MHz, CDCl3): δ 8.51 (s, 1H), 8.45 (s, 1H), 8.27 (d, J=4.5 Hz, 1H), 8.08 (d, J=8 Hz, 1H), 7.95 (d, J=9 Hz, 1H), 7.06 (d, J=8.5 Hz, 1H), 6.82 (m, 3H), 6.71 (s, 1H), 6.37 (s, 1H), 3.64 (t, J=5.5 Hz, 2H), 3.56 (t, J=5.5 Hz, 2H), 2.63 (m, 2H), 2.49 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 165.15, 163.96, 161.99, 154.67, 153.88, 153.79, 145.40, 143.56, 141.00, 140.15, 140.07, 139.38, 136.97, 136.44, 127.78, 124.64, 123.69, 122.49, 122.23, 121.97, 117.60, 112.87, 112.70, 111.71, 107.56, 107.37, 45.59, 44.54, 35.70, 29.18; m/z (473.4 M+ H+); HPLC: 96.6%.

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 (35% acetone in hexane)

Sources & evidence

ORD record
ord-328d849ffd6a4685b6b19a480265e820
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

Loading…