Phenyl pyridin-3-ylcarbamate → 4-(fluoro(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylene)-N-(pyridin-3-yl)piperidine-1-carboxamide

HRID 1666490

Reaction equation

HRID 1666490 reaction equation
[F:1][C:2](=[C:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)[C:3]1[CH:4]=[C:5]([CH:17]=[CH:18][CH:19]=1)[O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][N:8]=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>CS(C)=O.C(N(CC)CC)C.O>[F:1][C:2]([C:3]1[CH:19]=[CH:18][CH:17]=[C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:15])([F:16])[F:14])=[CH:9][N:8]=2)[CH:4]=1)=[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 2

HCID 6935890Phenyl pyridin-3-ylcarbamateHCID 668762662-(3-(Fluoro(piperidin-4-ylidene)methyl)phenoxy)-5-(trifluoromethyl)pyridine

Product 1

HCID 668755014-(fluoro(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylene)-N-(pyridin-3-yl)piperidine-1-carboxamideYield 74.6%

Reagents, catalysts & solvents 3

HCID 8471TriethylamineCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of 2-(3-(fluoro(piperidin-4-ylidene)methyl)phenoxy)-5-(trifluoromethyl)pyridine (110 mg, 0.312 mmol) and phenyl pyridin-3-ylcarbamate (66.8 mg, 0.312 mmol) in DMSO (2 mL) under N2 was added 3 drops of triethyl amine and the reaction mixture was stirred for 12 h. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed several times with water to remove the excess DMSO. The title compound was crystallized from CH2Cl2 and hexane to give the pure title compound (110 mg). 1H NMR (500 MHz, CDCl3): δ 2.5 (brs, 2H), 2.6 (brs, 2H), 3.7 (brs, 2H), 3.8 (brs, 2H), 7.0 (d, 1H, J=8.5 Hz), 7.1-7.3 (m, 3H), 7.4 (t, 1H, J=8.5), 7.7 (d, 1H, J=5.5 Hz), 7.9 (d, 1H, J=8 Hz), 8.0 (s, 1H), 8.4 (s, 1H), 9.2 (d, 1H, J=8.5 Hz), 9.6 (brs, 1H), 9.8 (brs, 1H); 13CNMR (125 MHz, CDCl3): 11.4, 14.3, 22.6, 25.5, 27.7, 31.5, 40.8, 44.1, 44.4, 53.4, 111.6, 114.0, 115.5, 119.8, 121.3, 121.4, 121.7, 122.5, 123.8, 125.3, 128.2, 129.6, 133.5, 133.8, 136.8, 140.5, 142.8, 145.3, 151.8, 153.0, 154.7, 156.7, 165.4; m/z (473.3 M+ H+); HPLC: 94.2%.

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed several times with water
  3. customto remove the excess DMSO
  4. customThe title compound was crystallized from CH2Cl2 and hexane

Sources & evidence

ORD record
ord-f0ad3a981ac44d3d95de15b38792b601
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Linked notes

Loading…