Cesium fluoride → HCID 58438550, compound

HRID 1898639Notes

Reaction equation

HRID 1898639 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:45])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[N:25]=[CH:26][N:27]([C:29]5[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=5[F:36])[CH:28]=4)[N:22]=3)[N:17](COCC[Si](C)(C)C)[CH:16]=2)=[O:14])[CH:9]2[CH2:11][CH2:10]2)[CH2:4]1)#[N:2].C1OCCOCCOCCOCCOCCOC1.[F-].[Cs+]>C(#N)C>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:45])[C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[N:25]=[CH:26][N:27]([C:29]5[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:30]=5[F:36])[CH:28]=4)[N:22]=3)[NH:17][CH:16]=2)=[O:14])[CH:9]2[CH2:10][CH2:11]2)[CH2:4]1)#[N:2]

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 2855718-Crown-6HCID 67386628HCID 67386628, compound

Product 1

HCID 58438550HCID 58438550, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 2-[1-(2,5-difluoro-phenyl)-1H-imidazol-4-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (0.037 g, 0.058 mmol), 18-crown-6 (0.016 g, 0.058 mmol) and cesium fluoride (0.093 g, 0.58 mmol) in 1 mL of acetonitrile was stirred at 75° C. for 5 d, then concentrated. The resulting residue was partitioned between 5 mL of a 1 M citric acid solution and 5 mL of dichloromethane. The aqueous layer was extracted with two 5 mL portions of dichloromethane. The combined organic layers were dried over Na2SO4, filtered and concentrated. Dichloromethane (1 mL) and 1 mL of trifluoroacetic acid were added, and the yellow solution was stirred 2 h, then concentrated. Dichloromethane (0.5 mL) and 0.5 mL of ethylene diamine were added, and the yellow-orange solution was stirred 1 h. The solution was partitioned between 10 mL of ethyl acetate and 5 mL of water, and the aqueous layer was extracted with 10 mL of ethyl acetate. The combined organic layers were dried over Na2SO4, filtered and concentrated. Column chromatography (0->10% MeOH/EtOAc) afforded 0.0055 g (19%) of 2-[1-(2,5-difluoro-phenyl)-1H-imidazol-4-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a pale yellow solid. MS: (M−H)−=501.

Workup

  1. concentrationconcentrated
  2. customThe resulting residue was partitioned between 5 mL of a 1 M citric acid solution and 5 mL of dichloromethane
  3. extractionThe aqueous layer was extracted with two 5 mL portions of dichloromethane
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionDichloromethane (1 mL) and 1 mL of trifluoroacetic acid were added
  8. concentrationconcentrated
  9. additionDichloromethane (0.5 mL) and 0.5 mL of ethylene diamine were added
  10. stirringthe yellow-orange solution was stirred 1 h
  11. customThe solution was partitioned between 10 mL of ethyl acetate and 5 mL of water
  12. extractionthe aqueous layer was extracted with 10 mL of ethyl acetate
  13. dry with materialThe combined organic layers were dried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-0e52f1f782834f4b924ef856c61ff4e0
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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