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Diethyl Ether → (S)-1-(1-(5-chloropyrazin-2-yl)piperidin-4-yl)-3-(2,5-difluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one

HRID 407891
ノート
印刷プレビュー

反応式

HRID 407891 の反応式
[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[C:5]([F:12])=[CH:4][C:3]=1[NH:13][C@H:14]1[CH2:18][CH2:17][N:16]([CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[C:15]1=[O:25].CCN(C(C)C)C(C)C.[Cl:35][C:36]1[CH:41]=[N:40][C:39](Cl)=[CH:38][N:37]=1.CCOCC>CN(C=O)C.[Cl-].[Na+].O>[Cl:35][C:36]1[N:37]=[CH:38][C:39]([N:22]2[CH2:23][CH2:24][CH:19]([N:16]3[CH2:17][CH2:18][C@H:14]([NH:13][C:3]4[CH:4]=[C:5]([F:12])[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:7][C:2]=4[F:1])[C:15]3=[O:25])[CH2:20][CH2:21]2)=[N:40][CH:41]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 3283Diethyl EtherHCID 81531DiisopropylethylamineHCID 3362242,5-DichloropyrazineHCID 66800289(S)-3-(2,5-difluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one2 回

生成物 1

HCID 86688082(S)-1-(1-(5-chloropyrazin-2-yl)piperidin-4-yl)-3-(2,5-difluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one収率 42.5%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
100 °C

実験手順

To a solution of (S)-3-(2,5-difluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (Table 2, compound 1; 1.5 g, 4.02 mmol) and DIEA (3.50 mL, 20.1 mmol) in DMF (15 mL) was added 2,5-dichloropyrazine (1.20 g, 8.03 mmol). This mixture was heated to 100° C. for 3 hours under nitrogen. The mixture was poured into brine (150 mL) and extracted into ethyl acetate (3×500 mL). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give an oil. Ether (100 mL) was added and a precipitate formed overnight. The ether was decanted and the solid was triturated using ethanol (100 mL) at reflux with stirring for 5 minutes. The material was purified by column chromatography using 50% to 100% ethyl acetate/hexane. The resulting solid was dried over the weekend under high vacuum to provide the title compound (0.83 g, 39% yield). Mass spectrum (apci) m/z=486.1 (M+H).

後処理

  1. extractionextracted into ethyl acetate (3×500 mL)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give an oil
  6. customa precipitate formed overnight
  7. customThe ether was decanted
  8. customthe solid was triturated
  9. temperatureat reflux
  10. customThe material was purified by column chromatography
  11. customThe resulting solid was dried over the weekend under high vacuum

出典と根拠

ORDレコード
ord-70d50193066f4a868e3bbea0105f3615
出典データセット
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08754226B2

反応ノート

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