Sodium cyanoborohydride → 7-chloro-6-(((1-(2-(2-oxo-1,7-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)amino)methyl)-2H-pyrido(3,2-b)(1,4)thiazin-3(4H)-one

HRID 1510748

Reaktionsgleichung

Reaktionsgleichung von HRID 1510748
Cl.[NH2:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][N:11]2[C:20]3[C:15](=[CH:16][CH:17]=[N:18][CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:21])[CH2:5][CH2:4]1.C[O-].[Na+].CO.[Cl:27][C:28]1[C:37]([CH:38]=O)=[N:36][C:35]2[NH:34][C:33](=[O:40])[CH2:32][S:31][C:30]=2[CH:29]=1.C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[Cl:27][C:28]1[C:37]([CH2:38][NH:2][CH:3]2[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][N:11]3[C:20]4[C:15](=[CH:16][CH:17]=[N:18][CH:19]=4)[CH:14]=[CH:13][C:12]3=[O:21])[CH2:5][CH2:4]2)=[N:36][C:35]2[NH:34][C:33](=[O:40])[CH2:32][S:31][C:30]=2[CH:29]=1

Komponenten

7

Edukt 4

HCID 5003444Sodium cyanoborohydrideHCID 218735897-Chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde2×HCID 23694274Sodium methanolate methanolHCID 689250331-(2-(4-aminopiperidin-1-yl)ethyl)-1,7-naphthyridin-2(1H)-one hydrochloride

Produkt 1

HCID 248641977-chloro-6-(((1-(2-(2-oxo-1,7-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)amino)methyl)-2H-pyrido(3,2-b)(1,4)thiazin-3(4H)-oneAusbeute 89,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 887MethanolLösungsmittel

Versuchsvorschrift

To a suspension of 0.10 g of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,7-naphthyridin-2(1H)-one hydrochloride in 3 mL of methanol, 0.15 mL of a 28% sodium methoxide/methanol solution and 15 μL of acetic acid were added. Thereto were added 51 mg of 7-chloro-3-oxo-3,4-dihydro-2H-pyrido(3,2-b)(1,4)thiazine-6-carbaldehyde and 0.20 g of molecular sieves 3A, and the mixture was stirred at room temperature for 30 minutes. Thereto was added 33 mg of sodium cyanoborohydride, and the mixture was stirred at room temperature for 1 hour 30 minutes. Thereto was added 51 mg of 7-chloro-3-oxo-3,4-dihydro-2H-pyrido(3,2-b)(1,4)thiazine-6-carbaldehyde, and the mixture was stirred at room temperature for 2 hours. The insoluble substance was filtered off, and chloroform and a saturated aqueous sodium hydrogen carbonate solution were added thereto. The organic layer was separated, and washed sequentially with water and a saturated aqueous sodium chloride solution. The organic layer was 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 10:1 to obtain 97 mg of 7-chloro-6-(((1-(2-(2-oxo-1,7-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)amino)methyl)-2H-pyrido(3,2-b)(1,4)thiazin-3(4H)-one as a white solid.

Aufarbeitung

  1. additionwere added
  2. stirringthe mixture was stirred at room temperature for 1 hour 30 minutes
  3. stirringthe mixture was stirred at room temperature for 2 hours
  4. filtrationThe insoluble substance was filtered off
  5. additionchloroform and a saturated aqueous sodium hydrogen carbonate solution were added
  6. customThe organic layer was separated
  7. washwashed sequentially with water
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  9. distillationthe solvent was distilled off under reduced pressure
  10. customThe resultant residue was purified by basic silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-5d7cc7920afc4f71aa912fd7ef20ef21
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08211908B2

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