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

HRID 1094785

Reaktionsgleichung

Reaktionsgleichung von HRID 1094785
[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]

Komponenten

9

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6228DimethylformamideKatalysatorHCID 1049PyridineLösungsmittelHCID 6342AcetonitrileLösungsmittel2×HCID 24386Thionyl ChlorideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-46100b110fba4c5cba629e80ff367c95
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08134007B2

Verknüpfte Notizen

Wird geladen…