Hydrochloric Acid → 2-(tert-butylamino)-N-(2,3-dichlorophenyl)pyridine-3-carboxamide

HRID 1518504

Reaktionsgleichung

Reaktionsgleichung von HRID 1518504
C(NC1C(C(NC2C=CC=C(F)C=2F)=[O:13])=CC=CN=1)(C)(C)C.C[O:24]C1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=S)=CC=1.Cl.N([O-])=O.[Na+].[OH-].[Na+].[C:52]([NH:56][C:57]1[C:62]([C:63]2[N:67]([C:68]3[CH:73]=[CH:72][CH:71]=[C:70]([Cl:74])[C:69]=3[Cl:75])N=NN=2)=[CH:61][CH:60]=[CH:59][N:58]=1)([CH3:55])([CH3:54])[CH3:53].[C:76]([NH:80][C:81]1[C:86]([C:87]2[N:91]([C:92]3[CH:97]=[CH:96][CH:95]=[C:94]([Cl:98])[C:93]=3[F:99])N=NN=2)=[CH:85][CH:84]=[CH:83][N:82]=1)([CH3:79])([CH3:78])[CH3:77]>C1(C)C=CC=CC=1.O>[C:52]([NH:56][C:57]1[C:62]([C:63]([NH:67][C:68]2[CH:73]=[CH:72][CH:71]=[C:70]([Cl:74])[C:69]=2[Cl:75])=[O:13])=[CH:61][CH:60]=[CH:59][N:58]=1)([CH3:55])([CH3:54])[CH3:53].[C:76]([NH:80][C:81]1[C:86]([C:87]([NH:91][C:92]2[CH:97]=[CH:96][CH:95]=[C:94]([Cl:98])[C:93]=2[F:99])=[O:24])=[CH:85][CH:84]=[CH:83][N:82]=1)([CH3:79])([CH3:78])[CH3:77]

Komponenten

11

Edukt 7

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 87949Lawesson's reagentHCID 23668193Sodium NitriteHCID 581794432-(tert-butylamino)-N-(2,3-difluorophenyl)pyridine-3-carboxamideHCID 66868353N-tert-butyl-3-(1-(3-chloro-2-fluorophenyl)-1H-tetrazol-5-yl)pyridin-2-amineHCID 66868400N-tert-butyl-3-(1-(2,3-dichlorophenyl)-1H-tetrazol-5-yl)pyridin-2-amine

Produkt 2

HCID 668663562-(tert-butylamino)-N-(2,3-dichlorophenyl)pyridine-3-carboxamideHCID 668679862-(tert-butylamino)-N-(3-chloro-2-fluorophenyl)pyridine-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Crude 2-(tert-butylamino)-N-(2,3-difluorophenyl)pyridine-3-carboxamide (1.5 g) was dissolved in dry toluene (24 mL), combined with Lawesson's reagent (1.4 g, 0.7 eq), heated at 90° C. for 10 hours, then evaporated to near dryness. The residue was diluted DCM (20 mL) and EtOH (20 mL) and treated with NH2NH2. The mixture was stirred at RT for 2 hours then concentrated in vacuo. The residue was diluted with Et2O and washed with sat NaHCO3 three times. The Et2O layer was washed with 6N HCl solution (2×20 mL), and the combined HCl extracts treated with NaNO2 (3 eq) in water at RT for 30 min. The resulting mixture was neutralized with 6N NaOH (to pH 7-8) and extracted with EtOAc. The combined extracts were dried over MgSO4, filtered, and concentrated in vacuo to afford crude N-tert-butyl-3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-2-amine. Using the same procedure, N-tert-butyl-3-(1-(2,3-dichlorophenyl)-1H-tetrazol-5-yl)pyridin-2-amine and N-tert-butyl-3-(1-(3-chloro-2-fluorophenyl)-1H-tetrazol-5-yl)pyridin-2-amine can be produced from 2-(tert-butylamino)-N-(2,3-dichlorophenyl)pyridine-3-carboxamide and 2-(tert-butylamino)-N-(3-chloro-2-fluorophenyl)pyridine-3-carboxamide, respectively.

Aufarbeitung

  1. customevaporated
  2. additiontreated with NH2NH2
  3. concentrationthen concentrated in vacuo
  4. additionThe residue was diluted with Et2O
  5. washwashed
  6. washThe Et2O layer was washed with 6N HCl solution (2×20 mL)
  7. extractionextracted with EtOAc
  8. dry with materialThe combined extracts were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto afford crude N-tert-butyl-3-(1-(2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-2-amine

Quellen und Nachweise

ORD-Eintrag
ord-70269b231de943298810803b191029b0
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08232406B2

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