Oxalyl chloride → 3-cyclopropyl-N-[3-({2-[(cyclopropylcarbonyl)amino][1,2,4]triazolo[1,5-a]pyridin-6-yl}oxy)phenyl]-1-methyl-1H-pyrazole-4-carboxamide

HRID 1874478

Reaktionsgleichung

Reaktionsgleichung von HRID 1874478
[CH:1]1([C:4]2[C:8]([C:9]([OH:11])=O)=[CH:7][N:6]([CH3:12])[N:5]=2)[CH2:3][CH2:2]1.C1(C2N(C)N=CC=2C(O)=O)CC1.C(Cl)(=O)C(Cl)=O.[NH2:31][C:32]1[CH:33]=[C:34]([CH:51]=[CH:52][CH:53]=1)[O:35][C:36]1[CH:37]=[CH:38][C:39]2[N:40]([N:42]=[C:43]([NH:45][C:46]([CH:48]3[CH2:50][CH2:49]3)=[O:47])[N:44]=2)[CH:41]=1>O1CCCC1.CN(C)C=O.O>[CH:1]1([C:4]2[C:8]([C:9]([NH:31][C:32]3[CH:53]=[CH:52][CH:51]=[C:34]([O:35][C:36]4[CH:37]=[CH:38][C:39]5[N:40]([N:42]=[C:43]([NH:45][C:46]([CH:48]6[CH2:49][CH2:50]6)=[O:47])[N:44]=5)[CH:41]=4)[CH:33]=3)=[O:11])=[CH:7][N:6]([CH3:12])[N:5]=2)[CH2:2][CH2:3]1

Komponenten

8

Edukt 4

HCID 65578Oxalyl chlorideHCID 195767943-cyclopropyl-1-methyl-1H-pyrazole-4-carboxylic acidHCID 290492885-cyclopropyl-1-methyl-1H-pyrazole-4-carboxylic acidHCID 57749117N-[6-(3-aminophenoxy)[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide

Produkt 1

HCID 577491363-cyclopropyl-N-[3-({2-[(cyclopropylcarbonyl)amino][1,2,4]triazolo[1,5-a]pyridin-6-yl}oxy)phenyl]-1-methyl-1H-pyrazole-4-carboxamideAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideKatalysatorHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a mixture of 3-cyclopropyl-1-methyl-1H-pyrazole-4-carboxylic acid and 5-cyclopropyl-1-methyl-1H-pyrazole-4-carboxylic acid (430 mg, 2.59 mmol) in tetrahydrofuran (7 mL) were added oxalyl chloride (338 μL, 3.87 mmol) and N,N-dimethylformamide (1 drop), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in N,N-dimethylacetamide (3 mL). N-[6-(3-Aminophenoxy)[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide (400 mg, 1.29 mmol) was added with stirring under ice-cooling, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (NH silica gel, hexane/ethyl acetate=70/30→0/100), and then by column chromatography (silica gel, ethyl acetate/methanol=95/5) and recrystallized from ethyl acetate to give the title compound (120 mg, 20%) as a white solid.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in N,N-dimethylacetamide (3 mL)
  3. stirringwith stirring under ice-
  4. temperaturecooling
  5. stirringthe mixture was stirred at room temperature for 15 hr
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with water and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltrated
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe residue was purified by column chromatography (NH silica gel, hexane/ethyl acetate=70/30→0/100)
  12. customby column chromatography (silica gel, ethyl acetate/methanol=95/5) and recrystallized from ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-40f2425bff2e4fb1b4417beee88a7e0e
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08304557B2

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