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

HRID 253951

反応式

HRID 253951 の反応式
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]

参加物

11

反応物 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

生成物 2

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
90 °C

実験手順

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 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.

後処理

  1. customevaporated
  2. additiontreated with NH2NH2
  3. concentrationthen concentrated in vacuo
  4. additionThe residue was diluted with Et2O
  5. washwashed
  6. washThe Et2O layer 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

出典と根拠

ORDレコード
ord-4a74986685634b19bac18da731ce1829
出典データセット
uspto-grants-2011_01
特許番号
US07872031B2

関連ノート

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