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Sodium Bicarbonate → 3-[5-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-3-sulfonyl]-propionic acid methyl ester

HRID 2067977
ノート
印刷プレビュー

反応式

HRID 2067977 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:8]([NH:12][C:13]([C:15]2[CH:16]=[N:17][N:18]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[C:19]=2[CH3:20])=[O:14])[CH2:9][CH2:10][CH3:11])[CH:5]=[N:6][CH:7]=1.[CH3:28][O:29][C:30](=[O:36])[CH2:31][CH2:32][S:33]([O-:35])=[O:34].[Na+].[Cl-].[NH4+].[Na].C(=O)(O)[O-].[Na+]>CS(C)=O.[Cu]I>[N:6]1[CH:7]=[CH:2][CH:3]=[C:4]([CH:8]([NH:12][C:13]([C:15]2[CH:16]=[N:17][N:18]([C:21]3[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=3)[C:19]=2[CH3:20])=[O:14])[CH2:9][CH2:10][CH3:11])[CH:5]=1.[CH3:28][O:29][C:30](=[O:36])[CH2:31][CH2:32][S:33]([C:2]1[CH:7]=[N:6][CH:5]=[C:4]([CH:8]([NH:12][C:13]([C:15]2[CH:16]=[N:17][N:18]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[C:19]=2[CH3:20])=[O:14])[CH2:9][CH2:10][CH3:11])[CH:3]=1)(=[O:35])=[O:34]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 516892Sodium BicarbonateHCID 23665669Sodium 1-Methyl 3-SulfinopropionateHCID 444805971-(4-Chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-bromo-pyridin-3-yl)-butyl]-amideHCID 86657765Sodium ammonium chloride

生成物 2

HCID 444808683-[5-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-3-sulfonyl]-propionic acid methyl ester
収率 42%
HCID 444813731-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid (1-pyridin-3-yl-butyl)-amide収率 16%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 679Dimethyl Sulfoxide溶媒

実験手順

A solution of 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-bromo-pyridin-3-yl)-butyl]-amide (1.1 g, 2.5 mmol), copper(I) iodide (1.4 g, 7.4 mmol), sodium 3-methoxy-3-oxopropane-1-sulfinate (1.3 g, 7.4 mmol) in DMSO (10 mL) is heated at 130° C. for 1.5 hour. After cooling to room temperature, saturated aqueous sodium ammonium chloride (10 mL) is added and the resultant mixture is stirred for 1 hour. The crude mixture is poured into saturated aqueous sodium bicarbonate (250 mL) and extracted with EtOAc (1×250 mL, 2×100 mL). The combined organic layers are washed with brine (100 mL), dried over sodium sulfate, filtered and concentrated in vacuo. Purification by flash chromatography on silica gel (eluted with 25 to 75% EtOAc/hexanes) affords 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid (1-pyridin-3-yl-butyl)-amide (159 mg, 16%) and 3-[5-(1-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-3-sulfonyl]-propionic acid methyl ester (540 mg, 42%).

後処理

  1. extractionextracted with EtOAc (1×250 mL, 2×100 mL)
  2. washThe combined organic layers are washed with brine (100 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography on silica gel (eluted with 25 to 75% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-bbad6508b3f248269bb1ef59fe53c507
出典データセット
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08293917B2

反応ノート

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