Sodium Carbonate → (+/-)-1,4-dihydro-5-isopropoxy-2-methyl-4-(2-trifluoromethylphenyl)-1,6-naphthyridine-3-carboxylic acid 2-(N-benzyl-N-methylamino)-ethylamide dihydrochloride

HRID 580011

Reaktionsgleichung

Reaktionsgleichung von HRID 580011
C(Cl)(=O)C([Cl:4])=O.[CH:7]([O:10][C:11]1[N:20]=[CH:19][CH:18]=[C:17]2[C:12]=1[CH:13]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31]([F:34])([F:33])[F:32])[C:14]([C:22]([OH:24])=O)=[C:15]([CH3:21])[NH:16]2)([CH3:9])[CH3:8].[CH2:35]([N:42]([CH3:46])[CH2:43][CH2:44][NH2:45])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.CCCCCC.C(OCC)C.CN(C)C=O>[ClH:4].[ClH:4].[CH2:35]([N:42]([CH2:43][CH2:44][NH:45][C:22]([C:14]1[CH:13]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]([F:34])([F:33])[F:32])[C:12]2[C:17](=[CH:18][CH:19]=[N:20][C:11]=2[O:10][CH:7]([CH3:9])[CH3:8])[NH:16][C:15]=1[CH3:21])=[O:24])[CH3:46])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Komponenten

9

Edukt 4

HCID 10340Sodium CarbonateHCID 65578Oxalyl chlorideHCID 3014812(2-Aminoethyl)(benzyl)methylamineHCID 13670941(+)-1,4-Dihydro-5-isopropoxy-2-methyl-4-(2-trifluoromethylphenyl)-1,6-naphthyridine-3-carboxylic acid

Produkt 1

HCID 67906784(+/-)-1,4-dihydro-5-isopropoxy-2-methyl-4-(2-trifluoromethylphenyl)-1,6-naphthyridine-3-carboxylic acid 2-(N-benzyl-N-methylamino)-ethylamide dihydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8058HexaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

17 ml dry dimethylformamide in 40 ml dry dioxan are cooled to 0° C. and 1.0 g (7.9 mMole) oxalyl chloride added dropwise thereto under an atmosphere of nitrogen. After 20 minutes, 2.7 g (6.9 mMole) (±)-1,4-dihydro-5-isopropoxy-2-methyl-4-(2-trifluoromethylphenyl)-1,6-naphthyridine-3-carboxylic acid (European Patent Application 173 933) are added portionwise thereto at 0° C. and the reaction mixture is warmed to 20° C. After 30 minutes at 20° C., this solution is added dropwise to a solution, cooled to 0° C., of 2.6 g (15.8 mMole) N-benzyl-N-methylethylene-diamine in 20 ml n-hexane. After warming to 20° C., the reaction mixture is stirred for 30 minutes then, with renewed ice cooling, 2 N aqueous sodium carbonate solution is added dropwise thereto and the reaction mixture is extracted twice with dichloromethane. The dichloromethane solutions are washed with water and dried over anhydrous sodium sulphate. The solvent is removed in a vacuum and the residue is chromatographed on silica gel with dichloromethane/methanol (9:1 v/v). The fraction with the Rf of 0.5 is isolated, dissolved in diethyl ether and the dihydrochloride precipitated out with hydrogen chloride in diethyl ether. This is recrystallized twice from acetonitrile. There is obtained (±)-1,4-dihydro-5-isopropoxy-2-methyl-4-(2-trifluoromethylphenyl)-1,6-naphthyridine-3-carboxylic acid 2-(N-benzyl-N-methylamino)-ethylamide dihydrochloride in the form of colorless crystals; mp 178°-180° C.

Aufarbeitung

  1. waitAfter 30 minutes at 20° C.
  2. additionthis solution is added dropwise to a solution
  3. temperatureAfter warming to 20° C.
  4. extractionthe reaction mixture is extracted twice with dichloromethane
  5. washThe dichloromethane solutions are washed with water
  6. dry with materialdried over anhydrous sodium sulphate
  7. customThe solvent is removed in a vacuum
  8. customthe residue is chromatographed on silica gel with dichloromethane/methanol (9:1 v/v)
  9. customThe fraction with the Rf of 0.5 is isolated
  10. customthe dihydrochloride precipitated out with hydrogen chloride in diethyl ether
  11. customThis is recrystallized twice from acetonitrile

Quellen und Nachweise

ORD-Eintrag
ord-23f359d8d0164f9d96bf0d5021a6a8f6
Quelldatensatz
uspto-grants-1988_06
Patentnummer
US04751228

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