Cesium fluoride → 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-dimethylcarbamoyl-ethyl)-amide

HRID 446951Notes

Reaction equation

HRID 446951 reaction equation
[CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13]([NH:15][C@@H:16]([CH3:22])[C:17]([N:19]([CH3:21])[CH3:20])=[O:18])=[O:14])=[CH:11][N:10](COCC[Si](C)(C)C)[C:7]3=[N:8][CH:9]=2)[CH2:3][CH2:2]1.C1OCCOCCOCCOCCOCCOC1.[F-].[Cs+]>C(#N)C>[CH3:21][N:19]([CH3:20])[C:17]([C@@H:16]([NH:15][C:13]([C:12]1[C:6]2[C:7](=[N:8][CH:9]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[N:5]=2)[NH:10][CH:11]=1)=[O:14])[CH3:22])=[O:18]

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 2855718-Crown-6HCID 67388122(S)-2-cyclopropyl-N-(1-(dimethylamino)-1-oxopropan-2-yl)-5-((2-(trimethyl-silyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 533898222-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-dimethylcarbamoyl-ethyl)-amideYield 48%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (S)-2-cyclopropyl-N-(1-(dimethylamino)-1-oxopropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (150 mg, 0.35 mmol) in acetonitrile (15.8 mL) at room temperature was added 18-crown-6 (92 mg, 0.35 mmol) and cesium fluoride (528 mg, 3.48 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 preparative TLC (CH2Cl2/MeOH/NH4OH, 90:9.5:0.5) to give 48 mg (48%) of 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-dimethylcarbamoyl-ethyl)-amide as an off-white solid. MS: (M+H)+=302.

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 preparative TLC (CH2Cl2/MeOH/NH4OH, 90:9.5:0.5)

Sources & evidence

ORD record
ord-9c685fc84c984a5389615b4668b1f49c
Source dataset
uspto-grants-2013_07
Patent number
US08481541B2

Reaction notes

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