Water → 6-Chloro-2-methyl-4-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)pyridazin-3(2H)-one

HRID 337276Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 337276
[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([C:23](OC(C)(C)C)=O)[CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.O>C(O)=O.C=O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1

Komponenten

5

Edukt 2

HCID 962WaterHCID 66742247Tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate

Produkt 1

HCID 667423806-Chloro-2-methyl-4-(5-(1-methylpiperidin-4-yl)pyridin-2-ylamino)pyridazin-3(2H)-oneAusbeute 88,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 284Formic AcidLösungsmittelHCID 712FormaldehydeLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

The tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate (2.0 g, 4.76 mmol, Eq: 1.00) was dissolved in the solvent mixture of formic acid (40.0 ml) and formaldehyde, 37% (80.0 ml). The reaction mixture was stirred at 70° C. overnight until reaction was complete as determined by LCMS analysis, then cooled to ambient temperature. Water was added and the resultant aqueous mixture was washed with CH2Cl2 and the CH2Cl2 layer was discarded. The pH of the aqueous layer was adjusted to pH=12 carefully with solid K2CO3, which resulted in precipitation of a solid. The solid was collected by filtration, washed with water and dried in vacuum oven at 50° C. over 72 h to afford 1.4 g of the desired product. (M+H)+=334 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.84 (dd, J=8.31, 3.02 Hz, 4 H) 1.99-2.19 (m, 2 H) 2.35 (s, 3 H) 2.42-2.68 (m, 1 H) 3.02 (d, J=12.09 Hz, 2 H) 3.81 (s, 3 H) 6.86 (d, J=8.31 Hz, 1 H) 7.52 (dd, J=8.50, 2.46 Hz, 1 H) 8.16-8.33 (m, 3 H).

Aufarbeitung

  1. temperaturecooled to ambient temperature
  2. washthe resultant aqueous mixture was washed with CH2Cl2
  3. customresulted in precipitation of a solid
  4. filtrationThe solid was collected by filtration
  5. washwashed with water
  6. customdried in vacuum oven at 50° C. over 72 h

Quellen und Nachweise

ORD-Eintrag
ord-8e4065ef91c14634994c89a7ee86d81a
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889682B2

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