Cesium carbonate → (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(1-(2-(trifluoromethyl)pyrimidin-5-yl)piperidin-4-yl)pyrrolidin-2-one

HRID 408015

反応式

HRID 408015 の反応式
[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:12][C@H:13]1[CH2:17][CH2:16][N:15]([CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[C:14]1=[O:24].Br[C:26]1[CH:27]=[N:28][C:29]([C:32]([F:35])([F:34])[F:33])=[N:30][CH:31]=1.CC1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC(C)=CC=2)C2C=CC(C)=CC=2)C2C=CC(C)=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:12][C@H:13]1[CH2:17][CH2:16][N:15]([CH:18]2[CH2:23][CH2:22][N:21]([C:26]3[CH:27]=[N:28][C:29]([C:32]([F:35])([F:34])[F:33])=[N:30][CH:31]=3)[CH2:20][CH2:19]2)[C:14]1=[O:24]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 4189906(S)-(-)-2,2'-Bis(di-p-tolylphosphino)-1, 1'-binaphthylHCID 336979635-Bromo-2-(trifluoromethyl)pyrimidineHCID 66800375(S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one

生成物 1

HCID 54670711(S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(1-(2-(trifluoromethyl)pyrimidin-5-yl)piperidin-4-yl)pyrrolidin-2-one収率 23.2%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

反応条件

温度
110 °C

実験手順

A mixture of (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (Preparation E; 0.20 g, 0.56 mmol), 5-bromo-2-(trifluoromethyl)pyrimidine (0.15 g, 0.68 mmol), (S)-(−)-2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl (0.076 g, 0.11 mmol), Pd(OAc)2 (0.025 g, 0.11 mmol), and Cs2CO3 (0.92 g, 2.8 mmol) were combined in degassed toluene (6 mL) and stirred in a sealed tube at 110° C. overnight. The solution was cooled, quenched with water, extracted with EtOAc, dried over MgSO4, and concentrated. Flash chromatography of the crude product on silica followed by trituration of the isolated material with 9:1 hexanes:DCM gave a white solid that was filtered and dried. The material was characterized as (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(1-(2-(trifluoromethyl)pyrimidin-5-yl)piperidin-4-yl)pyrrolidin-2-one (0.064 g, 0.13 mmol, 23% yield). Mass spectrum (apci) m/z=502.1 (M+H). Optical purity was not determined.

後処理

  1. temperatureThe solution was cooled
  2. customquenched with water
  3. extractionextracted with EtOAc
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customDCM gave a white solid
  7. filtrationthat was filtered
  8. customdried

出典と根拠

ORDレコード
ord-def9e9028d28466e9147e4c47c9f13e5
出典データセット
uspto-grants-2014_06
特許番号
US08754226B2

関連ノート

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