Pyridine → N-(5-bromo-pyridin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

HRID 1355177

反応式

HRID 1355177 の反応式
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:20]N1C(=O)CCC1=O.[Cl:28][C:29]1[CH:30]=[C:31]([C@@H:39]([CH2:43][CH:44]2[CH2:48][CH2:47][CH2:46][CH2:45]2)[C:40]([OH:42])=O)[CH:32]=[CH:33][C:34]=1[S:35]([CH3:38])(=[O:37])=[O:36].[NH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][N:51]=1.N1C=CC=CC=1>C(Cl)Cl.O>[Br:20][C:53]1[CH:54]=[CH:55][C:50]([NH:49][C:40](=[O:42])[C@@H:39]([C:31]2[CH:32]=[CH:33][C:34]([S:35]([CH3:38])(=[O:36])=[O:37])=[C:29]([Cl:28])[CH:30]=2)[CH2:43][CH:44]2[CH2:48][CH2:47][CH2:46][CH2:45]2)=[N:51][CH:52]=1

参加物

8

反応物 5

HCID 1049PyridineHCID 104392-AminopyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acid

生成物 1

HCID 53778182N-(5-bromo-pyridin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide収率 76%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

A solution of triphenylphosphine (238 mg, 0.91 mmol) in methylene chloride (10 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (183 mg, 1.03 mmol). The reaction mixture was stirred at 0° C. until it was completely dissolved and became light purple in color. The reaction mixture was then treated with 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 97, 200 mg, 0.61 mmol). The reaction mixture was stirred at 0° C. for 20 min and then warmed to 25° C. where it was stirred for 30 min. After such time, the reaction mixture was treated with 2-aminopyridine (85 mg, 0.91 mmol) and pyridine (0.088 mL, 1.09 mmol), and the reaction mixture was stirred at 25° C. for 16 h. The reaction was then diluted with water (10 mL) and then extracted with methylene chloride (3×15 mL). The combined organic layers were then dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 60/40 hexanes/ethyl acetate) afforded N-(5-bromo-pyridin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (222 mg, 76%) as an off-white foam: [α]23589=−48.6° (c=0.105, chloroform); EI-HRMS m/e calcd for C20H22BrClN2O3S (M+) 484.0223, found 484.0223.

後処理

  1. dissolutionwas completely dissolved
  2. stirringThe reaction mixture was stirred at 0° C. for 20 min
  3. temperaturewarmed to 25° C. where it
  4. stirringwas stirred for 30 min
  5. stirringthe reaction mixture was stirred at 25° C. for 16 h
  6. extractionextracted with methylene chloride (3×15 mL)
  7. dry with materialThe combined organic layers were then dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-b6e052f7ad984e90a32c10ca74c907ce
出典データセット
uspto-grants-2007_05
特許番号
US07223868B2

関連ノート

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