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

HRID 446946Notes

Reaction equation

HRID 446946 reaction equation
[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]

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-2e854960599d423a95e925a4a7bddc74
Source dataset
uspto-grants-2013_07
Patent number
US08481541B2

Reaction notes

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