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

HRID 1666463Notes

Reaction equation

HRID 1666463 reaction equation
[Br: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)[N:27]=1.C(N(CC)CC)C>CS(C)=O.O>[Br: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[N:27]=[N:26][CH:31]=[CH:30][CH:29]=2)=[O:34])[CH2:22][CH2:21]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 20150036Phenyl pyridazin-3-ylcarbamateHCID 668769892-(3-Bromo-5-(piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine

Product 1

HCID 668757084-(3-bromo-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamideYield 66%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

2-(3-Bromo-5-(piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine (0.57 g, 1.379 mmol) and phenyl pyridazin-3-ylcarbamate (0.296 g, 1.38 mmol) were dissolved in DMSO (4 mL). Triethylamine (0.57 mL, 4.13 mmol) was added and 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 (37% acetone in hexane) to give the title compound (0.486 g, 66%). 1H NMR (500 MHz, DMSO-d6): δ 8.78 (s, 1H), 8.45 (s, 1H), 8.27 (s, 1H), 7.93 (d, J=8.5 Hz, 1H), 7.41 (dd, J=4.75 Hz, 1H), 7.24 (s, 1H), 7.20 (s, 1H), 7.04 (d, J=9 Hz, 1H), 6.94 (s, 1H), 6.35 (s, 1H), 3.69 (m, 2H), 3.60 (m, 2H), 2.58 (m, 2H), 2.17 (m, 2H). 13C NMR (125 MHz, CDCl3): δ 165.16, 156.80, 153.50, 145.43, 140.30, 139.57, 136.97, 128.86, 128.09, 124.66, 123.35, 122.86, 122.49, 122.24, 121.98, 120.73, 111.67, 45.55, 44.52, 35.74, 29.29, 29.18; m/z (534.1, 536.1, M+ H+); HPLC: 99.0%.

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 (37% acetone in hexane)

Sources & evidence

ORD record
ord-1f20ca3fed6d47c1b56b174de70afcef
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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