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

HRID 1094785

반응식

HRID 1094785 반응식
[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]

참가 물질

9

반응물 4

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

생성물 1

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

시약·촉매·용매 4

HCID 6228Dimethylformamide촉매HCID 1049Pyridine용매HCID 6342Acetonitrile용매2회HCID 24386Thionyl Chloride용매

반응 조건

온도
50 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-46100b110fba4c5cba629e80ff367c95
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08134007B2

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