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

HRID 1666483Notes

Reaction equation

HRID 1666483 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([NH:7][C:8](=O)[O:9]C2C=CC=CC=2)[CH:2]=1.FC(F)(F)C(O)=O.[C:24]1([C:30](=[C:48]2[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]2)[C:31]2[CH:32]=[C:33]([CH:45]=[CH:46][CH:47]=2)[O:34][C:35]2[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][N:36]=2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)CC)C.C(OCC)C>CS(C)=O.C(Cl)Cl>[C:24]1([C:30]([C:31]2[CH:47]=[CH:46][CH:45]=[C:33]([O:34][C:35]3[CH:40]=[CH:39][C:38]([C:41]([F:43])([F:44])[F:42])=[CH:37][N:36]=3)[CH:32]=2)=[C:48]2[CH2:53][CH2:52][N:51]([C:8]([NH:7][C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)=[O:9])[CH2:50][CH2:49]2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 6935890Phenyl pyridin-3-ylcarbamateHCID 866239142-(3-(Phenyl(piperidin-4-ylidene)methyl)phenoxy)-5-(trifluoromethyl)pyridine trifluoroacetate

Product 1

HCID 249676374-(phenyl(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylene)-N-(pyridin-3-yl)piperidine-1-carboxamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of phenyl pyridin-3-ylcarbamate (27.1 mg, 0.127 mmol) in DMSO (3 mL) was added 2-(3-(phenyl(piperidin-4-ylidene)methyl)phenoxy)-5-(trifluoromethyl)pyridine trifluoroacetate (52 mg, 0.13 mmol), followed by triethylamine (0.018 mL, 0.127 mmol). The reaction was stirred at 60° C. for 3 h and then cooled to RT. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed with water and saturated aqueous NH4Cl, dried and concentrated. Purification by silica gel column chromatography (0-5% MeOH/CH2Cl) gave an oil. Diethyether was added followed by CH2Cl2 and the title compound crashed out as a solid (9.2 mg, 13% yield). MS (APCI 10V) AP+ 531.23; 1H NMR (400 MHz, CDCl3) δ ppm 2.43 (t, 2H) 2.50 (t, 2H) 3.51-3.58 (m, 4H) 6.75 (s, 1H) 6.90-6.92 (m, 1H) 6.94-7.04 (m, 2H) 7.12 (dd, 2H) 7.17-7.23 (m, 3H) 7.26-7.37 (m, 3H) 7.86 (dd, 1H) 7.97 (dd, 1H) 8.23 (br. s., 1H) 8.42 (s, 2H).

Workup

  1. temperaturecooled to RT
  2. customThe reaction mixture was partitioned between water and ethyl acetate
  3. washThe organic layer was washed with water and saturated aqueous NH4Cl
  4. customdried
  5. concentrationconcentrated
  6. customPurification by silica gel column chromatography (0-5% MeOH/CH2Cl)
  7. customgave an oil

Sources & evidence

ORD record
ord-68281c0f4bcb47c0b00d06654f1ca333
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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