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 385635

反応式

HRID 385635 の反応式
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

参加物

7

反応物 4

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

生成物 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)-one収率 89.7%

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 887Methanol溶媒

実験手順

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 3 A, 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.

後処理

  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

出典と根拠

ORDレコード
ord-a2b9d576c40642f0b5669cd1589c8b05
出典データセット
uspto-grants-2013_02
特許番号
US08367831B2

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