Triethylamine → 4-(Bromo(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylene)-N-(pyridin-3-yl)piperidine-1-carboxamide

HRID 1666477Notes

Reaction equation

HRID 1666477 reaction equation
FC(F)(F)C(O)=O.[Br:8][C:9](=[C:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)[C:10]1[CH:11]=[C:12]([CH:24]=[CH:25][CH:26]=1)[O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][N:15]=1.[N:33]1[CH:38]=[CH:37][CH:36]=[C:35]([NH:39][C:40](=O)[O:41]C2C=CC=CC=2)[CH:34]=1.C(N(CC)CC)C>CS(C)=O>[Br:8][C:9]([C:10]1[CH:26]=[CH:25][CH:24]=[C:12]([O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:22])([F:23])[F:21])=[CH:16][N:15]=2)[CH:11]=1)=[C:27]1[CH2:32][CH2:31][N:30]([C:40]([NH:39][C:35]2[CH:34]=[N:33][CH:38]=[CH:37][CH:36]=2)=[O:41])[CH2:29][CH2:28]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 6935890Phenyl pyridin-3-ylcarbamateHCID 866239102-(3-(Bromo(piperidin-4-ylidene)methyl)phenoxy)-5-(trifluoromethyl)pyridine trifluoroacetate

Product 1

HCID 249676394-(Bromo(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylene)-N-(pyridin-3-yl)piperidine-1-carboxamideYield 62%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 2-(3-(bromo(piperidin-4-ylidene)methyl)phenoxy)-5-(trifluoromethyl)pyridine trifluoroacetate (624 mg, 0.995 mmol) and phenyl pyridin-3-ylcarbamate (213 mg, 0.995 mmol) in DMSO (5 mL) was treated with triethyamine (0.28 mL, 201 mg, 1.99 mmol) and the mixture was heated to 60° C. After 4 h, the reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated and the aqueous layer was extracted again with ethyl acetate. The combine organic layers were washed with brine and dried over magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (0-5% MeOH/CH2Cl2) to afford the title compound as a white foam (329 mg, 62% yield). MS (APCI 10V) AP+ 535.15; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.36 (2H) 2.65 (2H) 3.46 (2H) 3.63 (2H) 6.99 (d, J=8.38 Hz, 1H) 7.05 (2H) 7.12 (dd, 1H) 7.35 (1H) 7.62 (1H) 7.87 (dd, J=8.87, 2.05 Hz, 1H) 8.13 (1H) 8.41 (1H) 8.65 (1H) 8.93 (1H) 9.20 (1H)

Workup

  1. customthe reaction mixture was partitioned between water and ethyl acetate
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted again with ethyl acetate
  4. washThe combine organic layers were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column chromatography (0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-456cae0bc39c45c0b6a2e15651942936
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

Loading…