Heptane → N-[6-Amino-5-(2,5-dichloro-3-methoxyphenyl)pyridin-2-yl]-4-methyl-1,2,5-oxadiazole-3-carboxamide

HRID 1094785

反応式

HRID 1094785 の反応式
[CH3:1][C:2]1[C:3]([C:7]([OH:9])=O)=[N:4][O:5][N:6]=1.C(Cl)(=O)C(Cl)=O.[Cl:16][C:17]1[C:22]([O:23][CH3:24])=[CH:21][C:20]([Cl:25])=[CH:19][C:18]=1[C:26]1[C:27]([NH2:33])=[N:28][C:29]([NH2:32])=[CH:30][CH:31]=1.CCCCCCC>S(Cl)(Cl)=O.CN(C)C=O.CC#N.N1C=CC=CC=1>[NH2:33][C:27]1[N:28]=[C:29]([NH:32][C:7]([C:3]2[C:2]([CH3:1])=[N:6][O:5][N:4]=2)=[O:9])[CH:30]=[CH:31][C:26]=1[C:18]1[CH:19]=[C:20]([Cl:25])[CH:21]=[C:22]([O:23][CH3:24])[C:17]=1[Cl:16]

参加物

9

反応物 4

HCID 8900HeptaneHCID 65578Oxalyl chlorideHCID 3147684-Methyl-1,2,5-oxadiazole-3-carboxylic acidHCID 666370413-(2,5-Dichloro-3-methoxyphenyl)-pyridine-2,6-diamine

生成物 1

HCID 25155961N-[6-Amino-5-(2,5-dichloro-3-methoxyphenyl)pyridin-2-yl]-4-methyl-1,2,5-oxadiazole-3-carboxamide収率 18%

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide触媒HCID 1049Pyridine溶媒HCID 6342Acetonitrile溶媒2 回HCID 24386Thionyl Chloride溶媒

反応条件

温度
50 °C

実験手順

4-Methyl-1,2,5-oxadiazole-3-carboxylic acid (0.3 g, 2.34 mmol) was stirred in thionyl chloride (10 ml) at 50° C. for 18 hours. A further 3 ml oxalyl chloride and 2 drops of dimethylformamide were added and the reaction stirred for a further 1.5 hours at 50° C. The reaction was concentrated in vacuo and azeotroped with dichloromethane. The residue (0.134 g, 0.915 mmol) was dissolved in CH3CN (1.83 ml) and added to a solution of 3-(2,5-dichloro-3-methoxyphenyl)-pyridine-2,6-diamine (Preparation 4, 0.200 g, 0.704 mmol) in anhydrous pyridine (10 ml). The reaction was heated at 60° C. for 24 hours. A further 0.88 equivalents of the acid chloride in CH3CN (0.091 g, in 1.2 ml) was added and the reaction stirred for a further 24 hours at 60° C. The reaction was partitioned between dichloromethane and a saturated aqueous solution of NaHCO3 before drying over Na2SO4 and concentrating in vacuo. The residue was purified by silica gel column chromatography eluting with 5:95 to 30:70 ethyl acetate:heptane to afford the title compound (0.050 g, 18% yield).

後処理

  1. concentrationThe reaction was concentrated in vacuo
  2. customazeotroped with dichloromethane
  3. temperatureThe reaction was heated at 60° C. for 24 hours
  4. stirringthe reaction stirred for a further 24 hours at 60° C
  5. customThe reaction was partitioned between dichloromethane
  6. dry with materiala saturated aqueous solution of NaHCO3 before drying over Na2SO4
  7. concentrationconcentrating in vacuo
  8. customThe residue was purified by silica gel column chromatography
  9. washeluting with 5:95 to 30:70 ethyl acetate

出典と根拠

ORDレコード
ord-46100b110fba4c5cba629e80ff367c95
出典データセット
uspto-grants-2012_03
特許番号
US08134007B2

関連ノート

読み込み中…