2,4,6-Trimethylpyridine → N-[(4-chlorophenyl)methyl]-6-[[2-hydroxyethyl(methyl)amino]methyl]-1-methyl-4-oxo-quinoline-3-carboxamide

HRID 1067988Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1067988
CS(Cl)(=O)=O.[Cl:6][C:7]1[CH:30]=[CH:29][C:10]([CH2:11][NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[C:21](CO)[CH:22]=3)[N:17]([CH3:28])[CH:16]=2)=[O:14])=[CH:9][CH:8]=1.N1C(C)=CC(C)=C[C:32]=1C.[CH3:40][NH:41][CH2:42][CH2:43][OH:44]>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:11][NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([CH2:40][N:41]([CH2:42][CH2:43][OH:44])[CH3:32])[CH:22]=3)[N:17]([CH3:28])[CH:16]=2)=[O:14])=[CH:29][CH:30]=1

Komponenten

8

Edukt 4

HCID 79532,4,6-TrimethylpyridineHCID 80162-(Methylamino)ethanolHCID 31297Methanesulfonyl chlorideHCID 15516933N-(4-Chlorobenzyl)-6-(hydroxymethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide

Produkt 1

HCID 16073861N-[(4-chlorophenyl)methyl]-6-[[2-hydroxyethyl(methyl)amino]methyl]-1-methyl-4-oxo-quinoline-3-carboxamideAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Methanesulfonyl chloride (0.065 mL) is added to a cold (0° C.) solution of N-(4-chlorobenzyl)-6-(hydroxymethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide (0.27 g) from Preparation No. 10, DMAP (0.017 g), and 2,4,6-collidine (0.12 mL) in anhydrous DMF (14 mL). The mixture is stirred at room temperature overnight and 2-(methylamino)ethanol (0.61 mL) is added. The reaction mixture is stirred at room temperature for 2 h, poured into water, and extracted with CH2Cl2 (3×). The organic layers are combined, dried (Na2SO4), filtered, and concentrated in vacuo. The residue is dissolved in CH2Cl2/MeOH and adsorbed onto silica. Purification by chromatography (eluent CH2Cl2 (1 L), 1.5% MeOH/CH2Cl2 (1 L), 2.5% MeOH/CH2Cl2 (1 L), 3.5% MeOH/CH2Cl2 (1 L), 5% MeOH/CH2Cl2 (1 L), 6% MeOH/CH2Cl2 (1 L)) affords the product as a clear residue. The residue is crystallized by addition of CH2Cl2/hexanes followed by removal of the solvents in vacuo to give 0.21 g (69%) of the title compound as a white solid.

Aufarbeitung

  1. stirringThe reaction mixture is stirred at room temperature for 2 h
  2. extractionextracted with CH2Cl2 (3×)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue is dissolved in CH2Cl2/MeOH
  7. customPurification by chromatography (eluent CH2Cl2 (1 L), 1.5% MeOH/CH2Cl2 (1 L), 2.5% MeOH/CH2Cl2 (1 L), 3.5% MeOH/CH2Cl2 (1 L), 5% MeOH/CH2Cl2 (1 L), 6% MeOH/CH2Cl2 (1 L))
  8. customaffords the product as a clear residue
  9. customThe residue is crystallized by addition of CH2Cl2/hexanes
  10. customfollowed by removal of the solvents in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-dacd1af6344f4640967b899037f3782b
Quelldatensatz
uspto-grants-2001_06
Patentnummer
US06248739B1

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