Cesium fluoride → 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-oxo-piperidin-3-yl)-amide

HRID 446946노트

반응식

HRID 446946 반응식
[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([NH:8][C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([CH:20]4[CH2:22][CH2:21]4)[N:18]=3)[N:13](COCC[Si](C)(C)C)[CH:12]=2)=[O:10])[C:3]1=[O:31].C1OCCOCCOCCOCCOCCOC1.[F-].[Cs+]>C(#N)C>[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([NH:8][C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([CH:20]4[CH2:22][CH2:21]4)[N:18]=3)[NH:13][CH:12]=2)=[O:10])[C:3]1=[O:31]

참가 물질

5

반응물 3

HCID 25953Cesium fluorideHCID 2855718-Crown-6HCID 673880382-cyclopropyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-oxo-piperidin-3-yl)-amide

생성물 1

HCID 533898492-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-oxo-piperidin-3-yl)-amide수율 59%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

To a solution of 2-cyclopropyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-oxo-piperidin-3-yl)-amide (145 mg, 0.33 mmol) in acetonitrile (14.2 mL) at room temperature was added 18-crown-6 (86.4 mg, 0.33 mmol) and cesium fluoride (497 mg, 3.27 mmol). The reaction mixture was heated to reflux temperature for 48 h then cooled to room temperature and filtered over a pad of celite. The filtrate was evaporated under vacuum and the crude residue was partitioned between EtOAc (25 mL) and water (25 mL). The organic extract was dried (Na2SO4) and evaporated under vacuum. The crude residue was purified by SiO2 column chromatography (25 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 90:9.5:0.5) to give 60 mg (59%) of 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-oxo-piperidin-3-yl)-amide as a white solid. MS: (M+H)+=314.

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux temperature for 48 h
  3. filtrationfiltered over a pad of celite
  4. customThe filtrate was evaporated under vacuum
  5. customthe crude residue was partitioned between EtOAc (25 mL) and water (25 mL)
  6. extractionThe organic extract
  7. dry with materialwas dried (Na2SO4)
  8. customevaporated under vacuum
  9. customThe crude residue was purified by SiO2 column chromatography (25 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 90:9.5:0.5)

출처 및 근거

ORD 기록
ord-2e854960599d423a95e925a4a7bddc74
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481541B2

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