Cesium carbonate → N-cyclopropyl-4-methyl-3-{[4-(pyridazin-3-ylmethoxy)benzoyl]amino}benzamide

HRID 550061Notes

Reaction equation

HRID 550061 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][OH:8])[N:2]=1.S(Cl)(Cl)=O.[CH:13]1([NH:16][C:17](=[O:35])[C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[C:20]([NH:25][C:26](=[O:34])[C:27]3[CH:32]=[CH:31][C:30](O)=[CH:29][CH:28]=3)[CH:19]=2)[CH2:15][CH2:14]1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-]>C(Cl)Cl.CS(C)=O>[CH:13]1([NH:16][C:17](=[O:35])[C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[C:20]([NH:25][C:26](=[O:34])[C:27]3[CH:28]=[CH:29][C:30]([O:8][CH2:7][C:3]4[N:2]=[N:1][CH:6]=[CH:5][CH:4]=4)=[CH:31][CH:32]=3)[CH:19]=2)[CH2:15][CH2:14]1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 24386Thionyl ChlorideHCID 30165Iodide IonHCID 27945753-(Hydroxymethyl)pyridazineHCID 66631169N-cyclopropyl-3-[(4-hydroxybenzoyl)amino]-4-methylbenzamide

Product 1

HCID 11475132N-cyclopropyl-4-methyl-3-{[4-(pyridazin-3-ylmethoxy)benzoyl]amino}benzamideYield 5.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-pyridazinylmethanol (140 mg, 1.27 mmol) in DCM (5 mL) was added thionyl chloride (103 μl, 1.42 mmol) and the resulting mixture stirred at room temperature for 4 h. The solvent was evaporated under reduced pressure and then to the residue in DMSO (4 mL) was added N-cyclopropyl-3-[(4-hydroxybenzoyl)amino]-4-methylbenzamide (197 mg, 0.636 mmol), cesium carbonate (621 mg, 1.91 mmol) and tetrabutylanunonium iodide (235 mg, 0.636 mmol) and the resulting mixture stirred at 60° C. for 16 h. The reaction mixture was added to a 20 g SCX column and product eluted with methanol. Concentration under reduced pressure gave impure product which was further purified on silica column chromatography eluting with 0-20% methanol/ 1% anmmonium hydroxide SG 0.88 in ethyl acetate. Evaporation and trituration with DCM and diethyl ether and filtration gave the title compound as a solid (15 mg, 5.9%); NMR Spectrum: (DMSOd6) 0.57 (m, 2H), 0.68 (m, 2H), 2.26 (s, 3H), 2.86 (m, 1H), 5.54 (s, 2H), 7.21 (d, 2H), 7.34 (d, 1H), 7.64 (m, 1H), 7.79 (m, 2H), 7.86 (m, 1H), 7.99 (m, 2H), 8.37 (m, 1H), 9.24 (m, 1H), 9.86 (s, 1H); Mass Spectrum: M−H− 401.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. stirringthe resulting mixture stirred at 60° C. for 16 h
  3. additionThe reaction mixture was added to a 20 g SCX column and product
  4. washeluted with methanol
  5. concentrationConcentration under reduced pressure
  6. customgave impure product which
  7. customwas further purified on silica column chromatography
  8. washeluting with 0-20% methanol/ 1% anmmonium hydroxide SG 0.88 in ethyl acetate
  9. customEvaporation and trituration
  10. filtrationwith DCM and diethyl ether and filtration

Sources & evidence

ORD record
ord-4d8fd3d190454258a2d6e28ddf991209
Source dataset
uspto-grants-2011_05
Patent number
US07943776B2

Reaction notes

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