Phenyl 6-methoxypyridin-3-ylcarbamate → 4-(fluoro(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylene)-N-(6-methoxypyridin-3-yl)piperidine-1-carboxamide

HRID 1666492Notes

Reaction equation

HRID 1666492 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.[CH3:26][O:27][C:28]1[N:33]=[CH:32][C:31]([NH:34][C:35](=O)[O:36]C2C=CC=CC=2)=[CH:30][CH:29]=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:35]([NH:34][C:31]2[CH:32]=[N:33][C:28]([O:27][CH3:26])=[CH:29][CH:30]=2)=[O:36])[CH2:22][CH2:21]1

Participants

6

Reactant 2

HCID 20185962Phenyl 6-methoxypyridin-3-ylcarbamateHCID 668762662-(3-(Fluoro(piperidin-4-ylidene)methyl)phenoxy)-5-(trifluoromethyl)pyridine

Product 1

HCID 249676364-(fluoro(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylene)-N-(6-methoxypyridin-3-yl)piperidine-1-carboxamideYield 44.7%

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 6-methoxypyridin-3-ylcarbamate (76.2 mg, 0.312 mmol) in DMSO (5 mL) under a N2 atmosphere was added 5 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 with water several times to remove the excess DMSO. The title compound was crystallized from hexane and diethyl ether to give the pure title compound (70 mg). 1H NMR (500 MHz, CDCl3): δ 2.5 (brs, 2H), 2.6 (brs, 2H), 3.5 (brs, 2H), 3.6 (brs, 2H), 4.0 (s, 3H), 6.7 (d, 1H, J=9 Hz), 7.0 (d, 1H, J=8.5 Hz), 7.1-7.3 (m, 3H), 7.4 (t, 1H, J=8.5 Hz), 7.9 (m, 1H), 8.1 (s, 1H), 8.4 (s, 1H); 13CNMR (125 MHz, CDCl3): 25.5, 27.7, 29.7, 44.0, 44.3, 53.8, 60.4, 110.3, 111.6, 114.2, 114.3, 121.3, 121.4, 121.7, 122.0, 122.5, 124.7, 125.3, 129.6, 129.9, 133.6, 133.8, 134.1, 136.8, 138.5, 145.3, 145.4, 149.9, 151.8, 153.0, 155.2, 160.3, 165.4; m/z (503.3 M+ H+); HPLC: 97.6%.

Workup

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

Sources & evidence

ORD record
ord-8919ee98671b4b708b8c8a5373c90fa1
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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