Sodium Bicarbonate → 7-methoxy-1-(2-(4-(((6-(3-thienyl)pyridin-2-yl)methyl)amino)piperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one hydrochloride

HRID 1510788Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1510788
[ClH:1].[NH2:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][N:11]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:23])[CH2:5][CH2:4]1.C[O-].[Na+].CO.[S:29]1[CH:33]=[CH:32][C:31]([C:34]2[N:39]=[C:38]([CH:40]=O)[CH:37]=[CH:36][CH:35]=2)=[CH:30]1.C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>CO.C(Cl)(Cl)Cl.C(O)(=O)C>[ClH:1].[CH3:22][O:21][C:18]1[CH:19]=[C:20]2[C:15]([CH:14]=[CH:13][C:12](=[O:23])[N:11]2[CH2:10][CH2:9][N:6]2[CH2:5][CH2:4][CH:3]([NH:2][CH2:40][C:38]3[CH:37]=[CH:36][CH:35]=[C:34]([C:31]4[CH:32]=[CH:33][S:29][CH:30]=4)[N:39]=3)[CH2:8][CH2:7]2)=[N:16][CH:17]=1

Komponenten

9

Edukt 5

HCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 162178896-(3-Thienyl)pyridine-2-carboxaldehydeHCID 23694274Sodium methanolate methanolHCID 689270711-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride

Produkt 1

HCID 689336997-methoxy-1-(2-(4-(((6-(3-thienyl)pyridin-2-yl)methyl)amino)piperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one hydrochlorideAusbeute 77,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittelHCID 887MethanolLösungsmittelHCID 6212ChloroformLösungsmittel

Versuchsvorschrift

To a suspension of 0.14 g of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochloride in 5 mL of methanol, 0.14 g of a 28% sodium methoxide/methanol solution, 46 mg of 6-(3-thienyl)pyridine-2-carbaldehyde, 0.10 g of molecular sieves 3A, 28 μL of acetic acid and 15 mg of sodium cyanoborohydride were added at room temperature, and the mixture was stirred at the same temperature for 3 hours. To the reaction mixture, a saturated aqueous sodium hydrogen carbonate solution and chloroform were added, the organic layer was separated, washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by basic silica gel column chromatography using an eluent of chloroform:methanol=30:1. To a solution of the resultant residue in 2 mL of ethyl acetate, 2 mL of a 4 mol/L hydrogen chloride/ethyl acetate solution was added, and the mixture was stirred at room temperature for 30 minutes. The solid was filtered off to obtain 97 mg of 7-methoxy-1-(2-(4-(((6-(3-thienyl)pyridin-2-yl)methyl)amino)piperidin-1-yl)ethyl)-1,5-naphthyridin-2(1H)-one hydrochloride as a yellow solid.

Aufarbeitung

  1. additionwere added at room temperature
  2. customthe organic layer was separated
  3. washwashed with a saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe resultant residue was purified by basic silica gel column chromatography
  7. additionTo a solution of the resultant residue in 2 mL of ethyl acetate, 2 mL of a 4 mol/L hydrogen chloride/ethyl acetate solution was added
  8. stirringthe mixture was stirred at room temperature for 30 minutes
  9. filtrationThe solid was filtered off

Quellen und Nachweise

ORD-Eintrag
ord-8a4f4878052f4a5baf3f65fd5db9fecc
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08211908B2

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