Phosgene → 1-(5-tert-butyl-2-methoxy-phenyl)-3-[4-(2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)-naphthalen-1-yl)-urea

HRID 2417007Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2417007
[C:1]([C:5]1[CH:6]=[C:7]([NH2:13])[C:8](=[CH:11][CH:12]=1)[O:9][CH3:10])([CH3:4])([CH3:3])[CH3:2].C(Cl)(Cl)=O.[N-:18]=[C:19]=[O:20].Cl.N[C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([C:33]2[CH:43]=[N:42][C:36]3[O:37][CH2:38][C:39](=[O:41])[NH:40][C:35]=3[CH:34]=2)=[CH:25][CH:24]=1.C(N(C(C)C)CC)(C)C>ClCCl.C([O-])(O)=O.[Na+].C1COCC1.CCOC(C)=O>[C:1]([C:5]1[CH:12]=[CH:11][C:8]([O:9][CH3:10])=[C:7]([NH:13][C:19]([NH:18][C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]([C:33]3[CH:43]=[N:42][C:36]4[O:37][CH2:38][C:39](=[O:41])[NH:40][C:35]=4[CH:34]=3)=[CH:25][CH:24]=2)=[O:20])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Komponenten

10

Edukt 5

HCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 105034IsocyanateHCID 41763185-tert-Butyl-o-anisidineHCID 226314107-(4-amino-naphthalen-1-yl)-1H-pyrido[2,3-b][1,4]oxazin-2-one hydrochloride

Produkt 1

HCID 102285491-(5-tert-butyl-2-methoxy-phenyl)-3-[4-(2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)-naphthalen-1-yl)-urea

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

To 4-tert-butyl-o-anisidine (0.035 g, 0.198 mmol) in 2 mL dichloromethane and 2 mL saturated aqueous NaHCO3 at 0° C., phosgene (˜2 M in toluene, 0.21 mL, 0.40 mmol) was added via syringe to the organic layer in one portion, while not stirring. The resulting mixture was stirred vigorously for 10 min, then the organic layer was separated and dried (MgSO4), filtered and concentrated in vacuo. To the resulting isocyanate solution was added a solution of 7-(4-amino-naphthalen-1-yl)-1H-pyrido[2,3-b][1,4]oxazin-2-one hydrochloride (Example 7) (72 mg, 0.220 mmol) and diisopropyl ethylamine (42 uL, 0.242 mmol) in 2 mL anhydrous THF. This mixture was stirred overnight, then diluted with EtOAc, washed with water and brine, dried (MgSO4), filtered and the solvents removed in vacuo. The residue was purified by preparative HPLC to afford 12 mg of the title compound, m.p.>200° C.

Aufarbeitung

  1. stirringThe resulting mixture was stirred vigorously for 10 min
  2. customthe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. stirringThis mixture was stirred overnight
  7. washwashed with water and brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customthe solvents removed in vacuo
  11. customThe residue was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-549cc07b5a20466a97ef9dd9ebb4aa1e
Quelldatensatz
uspto-grants-2004_11
Patentnummer
US06825184B2

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