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 385675ノート

反応式

HRID 385675 の反応式
[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

参加物

9

反応物 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

生成物 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 hydrochloride収率 77.9%

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒HCID 887Methanol溶媒HCID 6212Chloroform溶媒

実験手順

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 3 A, 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.

後処理

  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

出典と根拠

ORDレコード
ord-1d176aae7eff4b758ac1c965488c35d5
出典データセット
uspto-grants-2013_02
特許番号
US08367831B2

反応ノート

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