Methanamine, N-methoxy-, hydrochloride (1:1) → 1-[4-(Benzyloxy)-2-fluorophenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide

HRID 1407149Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1407149
Cl.[CH3:2][NH:3][O:4][CH3:5].CCN(C(C)C)C(C)C.C[Al](C)C.[CH2:19]([O:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[CH:38]=[C:37]([O:39][CH3:40])[C:36](=[O:41])[C:35]([C:42](OC)=[O:43])=[N:34]2)=[C:29]([F:46])[CH:28]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C(Cl)Cl>[CH2:19]([O:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[CH:38]=[C:37]([O:39][CH3:40])[C:36](=[O:41])[C:35]([C:42]([N:3]([O:4][CH3:5])[CH3:2])=[O:43])=[N:34]2)=[C:29]([F:46])[CH:28]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Komponenten

6

Edukt 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 16682925TrimethylaluminumHCID 59436166Methyl 1-[4-(benzyloxy)-2-fluorophenyl]-5-methoxy-4-oxo-1,4-dihydropyridazine-3-carboxylate

Produkt 1

HCID 866439351-[4-(Benzyloxy)-2-fluorophenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamideAusbeute 90 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of N,O-dimethylhydroxylamine hydrochloride (5.27 g, 54 mmol) and iPr2NEt (9.41 mL, 54 mmol) in CH2Cl2 (50 mL) was added AlMe3 (1.8 M solution in toluene, 30 mL, 54 mmol) slowly at 0° C. under Ar atmosphere. After stirring for 1 h, a solution of methyl 1-[4-(benzyloxy)-2-fluorophenyl]-5-methoxy-4-oxo-1,4-dihydropyridazine-3-carboxylate (8.07 g, 21 mmol) in CH2Cl2 (50 mL) was added slowly, and the mixture was stirred for 1 h at 0° C. The reaction mixture was poured into ice-water and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography eluting with AcOEt to give the title compound (7.79 g, 90% yield) as a pale yellow amorphous solid: 1H NMR (300 MHz, CDCl3): δ ppm 3.38 (3H, s), 3.70 (3H, s), 3.89 (3H, s), 5.11 (2H, s), 6.82-6.91 (2H, m), 7.33-7.45 (5H, m), 7.48-7.55 (1H, m), 7.73 (1H, d, J=1.9 Hz).

Aufarbeitung

  1. stirringthe mixture was stirred for 1 h at 0° C
  2. extractionextracted with AcOEt
  3. washThe extract was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography
  7. washeluting with AcOEt

Quellen und Nachweise

ORD-Eintrag
ord-ceabb1e2af6c42919ab48a58010d8d62
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08916566B2

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