Diethyl Ether → 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-hydroxy-3-methyl-cyclopentyl)-N-pyrazin-2-yl-propionamide

HRID 854831ノート

反応式

HRID 854831 の反応式
C[Mg]Br.CC[O:6][CH2:7][CH3:8].[Cl:9][C:10]1[CH:11]=[C:12]([CH:20]([CH2:30][CH:31]2[CH2:35]C[C:33](=O)[CH2:32]2)[C:21]([NH:23][C:24]2[CH:29]=[N:28][CH:27]=[CH:26][N:25]=2)=[O:22])[CH:13]=[CH:14][C:15]=1[S:16]([CH3:19])(=[O:18])=[O:17]>O1CCCC1>[Cl:9][C:10]1[CH:11]=[C:12]([CH:20]([CH2:30][CH:31]2[CH2:32][CH2:33][C:7]([OH:6])([CH3:8])[CH2:35]2)[C:21]([NH:23][C:24]2[CH:29]=[N:28][CH:27]=[CH:26][N:25]=2)=[O:22])[CH:13]=[CH:14][C:15]=1[S:16]([CH3:19])(=[O:17])=[O:18]

参加物

5

反応物 3

HCID 3283Diethyl EtherHCID 10477292Piragliatin;RO 4389620HCID 178418573HCID 178418573、化合物

生成物 1

HCID 100717912-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-hydroxy-3-methyl-cyclopentyl)-N-pyrazin-2-yl-propionamide収率 35.6%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

3.0M solution of methylmagnesium bromide in ether (2.53 mL, 7.59 mmol) cooled to 0° C. was treated dropwise with a solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclopentyl)-N-pyrazin-2-yl-propionamide (prepared as in Example 45, 0.10 g, 0.237 mmol) in tetrahydrofuran (1 mL). The resulting solution was stirred at 0° C. for 30 min, quenched with a saturated aqueous ammonium chloride solution (3 mL), and partitioned between a saturated aqueous ammonium chloride solution (20 mL) and ethyl acetate (25 mL). The aqueous layer was extracted with ethyl acetate (25 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 80% ethyl acetate/hexanes) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-hydroxy-3-methyl-cyclopentyl)-N-pyrazin-2-yl-propionamide (37 mg, 35%) as a yellow foam: mp 78-84° C. (foam to gel); (ES)+-HRMS m/e calcd for C20H24ClN3O4S (M+H)+ 438.1249. found 438.1254.

後処理

  1. customquenched with a saturated aqueous ammonium chloride solution (3 mL)
  2. custompartitioned between a saturated aqueous ammonium chloride solution (20 mL) and ethyl acetate (25 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (25 mL)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-bb0526429be7413b920cfc0e83c4f407
出典データセット
uspto-grants-2007_08
特許番号
US07259166B2

反応ノート

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