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

HRID 403033ノート

反応式

HRID 403033 の反応式
[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+]>C(Cl)Cl.CS(C)=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 67553Tetrabutylammonium Iodide触媒HCID 679Dimethyl Sulfoxide溶媒HCID 6344Dichloromethane溶媒

実験手順

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 tetrabutylammonium 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% ammonium 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.

後処理

  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% ammonium hydroxide SG 0.88 in ethyl acetate
  9. customEvaporation and trituration
  10. filtrationwith DCM and diethyl ether and filtration

出典と根拠

ORDレコード
ord-de40fcdc23334e96bae6b526281f90e6
出典データセット
uspto-grants-2014_06
特許番号
US08742124B2

反応ノート

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