Formaldehyde → N6-(1-Methyl-4-piperidylmethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide

HRID 853536Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 853536
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([CH:42]=[CH:43][C:44]=1[NH:45][C:46]([NH:48][CH:49]1[CH2:51][CH2:50]1)=[O:47])[O:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:40][CH3:41])=[C:20]([C:23]([NH:25][CH2:26][CH:27]3[CH2:32][CH2:31][N:30]([C:33](OC(C)(C)C)=O)[CH2:29][CH2:28]3)=[O:24])[CH:21]=2)[N:16]=[CH:15][CH:14]=1.C(=O)(O)[O-].[Na+].C=O.C([BH3-])#N.[Na+]>C(OCC)(=O)C.C(O)(=O)C>[CH3:33][N:30]1[CH2:29][CH2:28][CH:27]([CH2:26][NH:25][C:23]([C:20]2[CH:21]=[C:22]3[C:17](=[CH:18][C:19]=2[O:40][CH3:41])[N:16]=[CH:15][CH:14]=[C:13]3[O:12][C:11]2[CH:42]=[CH:43][C:44]([NH:45][C:46]([NH:48][CH:49]3[CH2:51][CH2:50]3)=[O:47])=[C:9]([Cl:8])[CH:10]=2)=[O:24])[CH2:32][CH2:31]1

Komponenten

8

Edukt 5

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 516892Sodium Bicarbonate2×HCID 5003444Sodium cyanoborohydrideHCID 22936930tert-Butyl 4-((((4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolyl)carbonyl)amino)methyl)-1-piperidinecarboxylate

Produkt 1

HCID 58931341N6-(1-Methyl-4-piperidylmethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamideAusbeute 58,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

After adding trifluoroacetic acid (1 ml) to tert-butyl 4-((((4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolyl)carbonyl)amino)methyl)-1-piperidinecarboxylate (249 mg, 0.40 mmol) at room temperature, the mixture was stirred for 2 hours. The reaction solution was poured into saturated aqueous sodium bicarbonate for neutralization and extracted 3 times with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate. After distilling off the solvent, the residue was dissolved in tetrahydrofuran (5 ml)-methanol (5 ml), and then 37% aqueous formaldehyde (0.5 ml), acetic acid (0.05 ml) and sodium cyanoborohydride (50 mg, 0.8 mmol) were added in that order at room temperature and the mixture was stirred for 1 hour. The reaction solution was distributed between ethyl acetate and saturated aqueous sodium bicarbonate, and the organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine and dried over anhydrous sodium sulfate. After distilling off the solvent, ethyl acetate was used for crystallization and the crystals were filtered out and blow-dried to obtain the title compound (125.6 mg, 0.233 mmol, 58.4%) as white crystals.

Aufarbeitung

  1. extractionextracted 3 times with ethyl acetate
  2. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  3. distillationAfter distilling off the solvent
  4. dissolutionthe residue was dissolved in tetrahydrofuran (5 ml)-methanol (5 ml)
  5. stirringthe mixture was stirred for 1 hour
  6. washthe organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. distillationAfter distilling off the solvent, ethyl acetate
  9. customwas used for crystallization
  10. filtrationthe crystals were filtered out and
  11. customblow-dried

Quellen und Nachweise

ORD-Eintrag
ord-e6822a223cb04865a4f22062aa47b468
Quelldatensatz
uspto-grants-2007_08
Patentnummer
US07253286B2

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