Water → 4-((6-phenoxypyridin-2-yl)methylene)-N-(pyridazin-3-yl)piperidine-1-carboxamide

HRID 1666515Notes

Reaction equation

HRID 1666515 reaction equation
F[C:2](F)(F)[C:3](O)=O.N1CCC(=C[C:15]2[CH:16]=[C:17]([CH:25]=[CH:26][CH:27]=2)[O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)CC1.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30]([NH:34][C:35](=[O:43])OC2C=CC=CC=2)[N:29]=1.C([N:46]([CH2:49][CH3:50])[CH2:47][CH3:48])C.O>CS(C)=O>[O:18]([C:19]1[N:20]=[C:21]([CH:2]=[C:3]2[CH2:48][CH2:47][N:46]([C:35]([NH:34][C:30]3[N:29]=[N:28][CH:33]=[CH:32][CH:31]=3)=[O:43])[CH2:49][CH2:50]2)[CH:22]=[CH:23][CH:24]=1)[C:17]1[CH:16]=[CH:15][CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 20150036Phenyl pyridazin-3-ylcarbamateHCID 66875752HCID 66875752, compound

Product 1

HCID 249662014-((6-phenoxypyridin-2-yl)methylene)-N-(pyridazin-3-yl)piperidine-1-carboxamideYield 30%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine trifluoroacetate (0.300 g), phenyl pyridazin-3-ylcarbamate (0.183 g, 1.40 equiv; Example 39, Step 2), and triethylamine (0.423 mL, 5.00 equiv) in dimethyl sulfoxide (2.0 mL, 0.30 M) was heated to 65° C. for 2 h. The reaction was cooled to room temperature. Water was added and then the solution was extracted with ethyl acetate (3×). The organic extracts were combined and washed with water, dried over magnesium sulfate, filtered, and concentrated. The residue was purified on a 12 g silica gel column using 20-50% ethyl acetate/dichloromethane over 60 minutes as the eluent. Combined product fractions and concentrated to give the title compound as a yellow foam. 0.071 g, 30% yield. 1H NMR (400 MHz, CDCl3) δ ppm 2.45 (2H, t, J=5.5 Hz), 2.59 (2H, t, J=5.5 Hz), 3.60 (2H, t, J=5.8 Hz), 3.70 (2H, t, J=5.8 Hz), 6.39 (1H, s), 6.90 (1H, d, J=8.2 Hz), 6.93-7.05 (4H, m), 7.34 (1H, t, J=8.0 Hz), 7.47 (1H, dd, J=9.4, 4.7 Hz), 7.63-7.72 (1H, m), 8.18 (1H, dd, J=1.9, 0.8 Hz), 8.45 (1H, d, J=9.0 Hz), 8.74 (1H, d, J=3.9 Hz).

Workup

  1. extractionthe solution was extracted with ethyl acetate (3×)
  2. washwashed with water
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified on a 12 g silica gel column
  7. customover 60 minutes
  8. concentrationCombined product fractions and concentrated

Sources & evidence

ORD record
ord-9500ec770c1a47b79a8e1ae80a36a10a
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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