Cesium fluoride → HCID 60036685, compound

HRID 1948954Notes

Reaction equation

HRID 1948954 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[C@@H:36]2[CH2:40][N:39]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[C@H:38]([C:48]([O:50][CH3:51])=[O:49])[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][C@H:36]3[CH2:40][N:39]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[C@H:38]([C:48]([O:50][CH3:51])=[O:49])[CH2:37]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 574768684-((3-Chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-olHCID 60036700HCID 60036700, compound

Product 1

HCID 60036685HCID 60036685, compoundYield 31.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Dimethylformamide (15 ml) was added to 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-hydroxyquinazoline (0.66 g; prepared as described in Example 22-preparation of starting materials), 1-tert-butyl 2-methyl (2S,4S)-4-[(4-nitrophenyl)sulfonyloxy]pyrrolidine-1,2-dicarboxylate (0.889 g) and cesium fluoride (0.941 g). The reaction mixture was then stirred at room temperature for 16 hours. The reaction mixture was evaporated under vacuum and the residue partitioned between ethyl acetate and water. The organics were washed with water and saturated brine and dried over magnesium sulfate. The product was then purified by column chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5). The fractions containing the expected product were combined and evaporated under vacuum to give 4-(3-chloro-2-fluoroanilino)-6-[(2S,4R)-1-(tert-butoxycarbonyl)-2-(methoxycarbonyl)pyrrolidin-4-yloxy]-7-methoxyquinazoline as a colourless gum (0.36 g); Mass Spectrum: (M+H)+ 547.

Workup

  1. customThe reaction mixture was evaporated under vacuum
  2. customthe residue partitioned between ethyl acetate and water
  3. washThe organics were washed with water and saturated brine
  4. dry with materialdried over magnesium sulfate
  5. customThe product was then purified by column chromatography
  6. washeluting
  7. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5)
  8. additionThe fractions containing the expected product
  9. customevaporated under vacuum

Sources & evidence

ORD record
ord-fc92d2a2d7a04723a89d7dd2a6179383
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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