Ammonium Chloride → Methyl 4-[(6-morpholin-4-yl-pyridazin-3-ylamino)-methyl]-benzoate

HRID 852919Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 852919
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl.[NH2:15][CH2:16][C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][CH:18]=1.[NH4+].[Cl-]>CC(O)C>[N:8]1([C:5]2[N:6]=[N:7][C:2]([NH:15][CH2:16][C:17]3[CH:18]=[CH:19][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:25][CH:26]=3)=[CH:3][CH:4]=2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1

Komponenten

5

Edukt 3

HCID 25517Ammonium ChlorideHCID 3210794-(6-Chloropyridazin-3-yl)morpholineHCID 2729253Methyl 4-(aminomethyl)benzoate hydrochloride

Produkt 1

HCID 58930537Methyl 4-[(6-morpholin-4-yl-pyridazin-3-ylamino)-methyl]-benzoateAusbeute 8,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To a solution of 64 (2.0 g, 10.0 mmol) and methyl 4-(aminomethyl)benzoate hydrochloride (2.2 g, 11.0 mmol) in i-PrOH (200 mL) was added NH4Cl (2.14 g, 40.0 mmol). The reaction mixture was heated at 150° C. for 72 h and concentrated. The residue was dissolved in water and the aqueous phase was extracted with. \the aqueous phase was separated, treated with 1N NaOH (pH 8) and extracted with EtOAc. The extract was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (MeOH/CH2Cl2: 2/98 to 5/95) to afford the title compound 65 (270 mg, 0.82 mmol, 8% yield). 1H NMR: (400 MHz, CDCl3) δ (ppm): 7.97 (d, J=8.0 Hz, 2H), 7.42 (d, J=8.0 Hz, 2H), 6.90 (d, J=9.2 Hz, 1H), 6.69 (d, J=9.2 Hz, 1H), 5.16-5.06 (bs, 1H), 4.67 (s, 2H), 3.90 (s, 3H), 3.82 (t, J=4.8 Hz, 4H), 3.41 (t, J=4.8 Hz, 4H).

Aufarbeitung

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in water
  3. extractionthe aqueous phase was extracted with
  4. custom\the aqueous phase was separated
  5. additiontreated with 1N NaOH (pH 8)
  6. extractionextracted with EtOAc
  7. dry with materialThe extract was dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography on silica gel (MeOH/CH2Cl2: 2/98 to 5/95)

Quellen und Nachweise

ORD-Eintrag
ord-89f41a02d34945428ae3af8a28b1dab5
Quelldatensatz
uspto-grants-2007_08
Patentnummer
US07253204B2

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