Hydrochloric Acid → 11-(3-Chloro-4-fluorobenzyl)-9-hydroxy-3,4,5,6,12,13-hexahydro-[1,4]oxazocino[3,4-a]-2,6-naphthyridine-1,8,10(11H)-trione

HRID 18030

Reaktionsgleichung

Reaktionsgleichung von HRID 18030
[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16](N(C)C)=[O:17])=[N:11][C:10]([OH:21])=[C:9]([OH:22])[C:8]=2[C:7]1=[O:23].C[O-:29].[Mg+2].C[O-].Br[CH2:34][CH2:35][CH2:36][CH2:37]Cl.Cl>CO.CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:22])[C:10](=[O:21])[N:11]3[CH2:37][CH2:36][CH2:35][CH2:34][O:17][C:16](=[O:29])[C:12]3=2)[C:7]1=[O:23]

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 813641-Bromo-4-chlorobutaneHCID 164537Methanol, magnesium salt (2:1)HCID 178484497HCID 178484497, Verbindung

Produkt 1

HCID 5934472111-(3-Chloro-4-fluorobenzyl)-9-hydroxy-3,4,5,6,12,13-hexahydro-[1,4]oxazocino[3,4-a]-2,6-naphthyridine-1,8,10(11H)-trione

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittel2×HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A mixture of 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-N,N-dimethyl-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxamide (0.80 g, 2.19 mmol; Example 1, step 9) and magnesium methoxide in methanol (10.6 mL, 6-10% methanol solution available from Aldrich) in DMSO (22 mL) was heated at 60° C. for 30 minutes. Methanol was exhaustively removed under vacuum over 45 minutes. The residual DMSO solution was treated with 1-bromo-4-chlorobutane (1.80 g, 10.50 mmol) and stirred at 60° C. under an atmosphere of nitrogen overnight. The reaction mixture was heated at 100° C. for 3 hrs. The reaction mixture was treated with dilute HCl. The solid precipitated was filtered, dissolved in DMSO, and subjected to reverse phase HPLC purification. Collection and lyophization of appropriate fractions provided the title compound.

Aufarbeitung

  1. customMethanol was exhaustively removed under vacuum over 45 minutes
  2. temperatureThe reaction mixture was heated at 100° C. for 3 hrs
  3. customThe solid precipitated
  4. filtrationwas filtered
  5. dissolutiondissolved in DMSO
  6. customphase HPLC purification
  7. customCollection and lyophization of appropriate fractions

Quellen und Nachweise

ORD-Eintrag
ord-2362b2ad6ef049cf9f91ea51891e3adc
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741315B2

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