Water → N-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide

HRID 1666521Notes

Reaction equation

HRID 1666521 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][C:5](=[CH:8][C:9]2[CH:10]=[C:11]([CH:23]=[CH:24][CH:25]=2)[O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][N:14]=2)[CH2:4][CH2:3]1.[CH:26]1([C:29]2[S:33][C:32]([NH:34][C:35](=O)[O:36]C3C=CC=CC=3)=[N:31][N:30]=2)[CH2:28][CH2:27]1.C(N(CC)CC)C.O>CS(C)=O>[CH:26]1([C:29]2[S:33][C:32]([NH:34][C:35]([N:2]3[CH2:7][CH2:6][C:5](=[CH:8][C:9]4[CH:25]=[CH:24][CH:23]=[C:11]([O:12][C:13]5[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:20])[F:21])=[CH:15][N:14]=5)[CH:10]=4)[CH2:4][CH2:3]3)=[O:36])=[N:31][N:30]=2)[CH2:28][CH2:27]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 19227158Phenyl 5-cyclopropyl-1,3,4-thiadiazol-2-ylcarbamateHCID 668761612-(3-(Piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine hydrochloride

Product 1

HCID 24966197N-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamideYield 42%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 2-(3-(piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine hydrochloride (0.100 g; Example 1a, Step 5), phenyl 5-cyclopropyl-1,3,4-thiadiazol-2-ylcarbamate (0.085 g, 1.2 equiv), and triethylamine (0.045 mL, 1.2 equiv) in dimethyl sulfoxide (1 mL, 0.3 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 (2×). The organic extracts were dried over magnesium sulfate, filtered, and concentrated. The residue was purified on a 12 g silica gel column using 10-30% ethyl acetate/dichloromethane over 30 minutes as the eluent to give the title compound as a white foam. 0.057 g, 42% yield. 1H NMR (400 MHz, CDCl3) δ ppm 0.98-1.07 (2H, m), 1.09-1.18 (2H, m), 2.15-2.25 (1H, m), 2.46 (2H, t, J=5.5 Hz), 2.60 (2H, t, J=5.5 Hz), 3.66 (2H, t, J=5.8 Hz), 3.76 (2H, t, J=5.9 Hz), 6.40 (1H, s), 6.95-7.04 (3H, m), 7.09 (1H, d, J=7.8 Hz), 7.37 (1H, t, J=7.8 Hz), 7.89 (1H, dd, J=8.6, 2.7 Hz), 8.43 (1H, dd, J=1.6, 0.8 Hz).

Workup

  1. extractionthe solution was extracted with ethyl acetate (2×)
  2. dry with materialThe organic extracts were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified on a 12 g silica gel column
  6. customover 30 minutes

Sources & evidence

ORD record
ord-1f579cbcf86e42f7bea0c468e71dd578
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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