Water → HCID 24966199, compound

HRID 1666519Notes

Reaction equation

HRID 1666519 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]=[C:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)[CH:17]=2)=[N:13][CH:14]=1.[N:29]1[CH:34]=[CH:33][CH:32]=[C:31]([NH:35][C:36](=O)[O:37]C2C=CC=CC=2)[N:30]=1.C(N(CC)CC)C.O>CS(C)=O>[F:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][C:16]2[CH:17]=[C:18]([CH:19]=[CH:20][CH:21]=2)[CH:22]=[C:23]2[CH2:24][CH2:25][N:26]([C:36]([NH:35][C:31]3[N:30]=[N:29][CH:34]=[CH:33][CH:32]=3)=[O:37])[CH2:27][CH2:28]2)=[N:13][CH:14]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 20150036Phenyl pyridazin-3-ylcarbamateHCID 66876197HCID 66876197, compound

Product 1

HCID 24966199HCID 24966199, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 5-fluoro-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine trifluoroacetate (0.466 g), phenyl pyridazin-3-ylcarbamate (0.274 g, 1.40 equiv), and triethylamine (0.634 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 times). 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 to give the title compound as a yellow foam. 0.155 g, 42% yield. 1H NMR (400 MHz, CDCl3) δ ppm 2.46 (2H, t, J=5.5 Hz), 2.59 (2H, t, J=5.5 Hz), 3.61 (2H, t, J=5.8 Hz), 3.71 (2H, t, J=5.8 Hz), 6.39 (1H, s), 6.84-6.99 (3H, m), 7.02 (1H, d, J=7.8 Hz), 7.34 (1H, t, J=7.8 Hz), 7.39-7.54 (2H, m), 8.02 (1H, d, J=3.1 Hz), 8.47 (1H, d, J=8.6 Hz), 8.74 (1H, d, J=3.5 Hz).

Workup

  1. extractionthe solution was extracted with ethyl acetate (3 times)
  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

Sources & evidence

ORD record
ord-2593945ce2dd4ade9f6e24981cac461b
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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