Cesium fluoride → HCID 68524581, compound

HRID 1948916

Reaction equation

HRID 1948916 reaction equation
[Cl:1][C:2]1[C:3]([F:22])=[C:4]([CH:19]=[CH:20][CH:21]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:17][CH3:18])=[C:13]([OH:16])[CH:14]=2)[N:9]=[CH:8][N:7]=1.[N+](C1C=CC(S(O[CH:36]2[CH2:41][CH2:40][CH2:39][N:38]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:37]2)(=O)=O)=CC=1)([O-])=O.[F-].[Cs+]>CN(C)C=O>[Cl:1][C:2]1[C:3]([F:22])=[C:4]([CH:19]=[CH:20][CH:21]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:17][CH3:18])=[C:13]([O:16][CH:40]3[CH2:41][CH2:36][CH2:37][N:38]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:39]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 57476868HCID 57476868, compoundHCID 86600822Tert-butyl 3-[(4-nitrophenyl)sulfonyloxy]piperidine-1-carboxylate

Product 1

HCID 68524581HCID 68524581, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Dimethylformamide (23 ml) was added to 4-(3-chloro-2-fluoroanilino)-6-hydroxy-7-methoxyquinazoline, tert-butyl 3-[(4-nitrophenyl)sulfonyloxy]piperidine-1-carboxylate (1.93 g) and cesium fluoride (2.28 g). The reaction mixture was then stirred at room temperature for 4 days. The reaction mixture was evaporated under vacuum and partitioned between methylene chloride and water. The solutions were filtered to remove insoluble solids and the methylene chloride was washed with water and saturated brine and adsorbed onto silica. The product was then purified by column chromatography on silica eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 94/6). The fractions containing the required product were combined and evaporated under vacuum to give 4-(3-chloro-2-fluoroanilino)-6-(1-tert-butoxycarbonylpiperidin-3-yloxy)-7-methoxyquinazoline as a yellow gum (0.67 g); Mass Spectrum: (M+H)+ 503.

Workup

  1. customThe reaction mixture was evaporated under vacuum
  2. custompartitioned between methylene chloride and water
  3. filtrationThe solutions were filtered
  4. customto remove insoluble solids
  5. washthe methylene chloride was washed with water and saturated brine
  6. customThe product was then purified by column chromatography on silica eluting
  7. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 94/6)
  8. additionThe fractions containing the required product
  9. customevaporated under vacuum

Sources & evidence

ORD record
ord-3465babe351542c8b5959908c6b9a417
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Linked notes

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