Dimethylformamide → HCID 68523595, compound

HRID 1948929Notes

Reaction equation

HRID 1948929 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][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37]2)(=O)=O)=CC=1)([O-])=O.[F-].[Cs+].CN(C)C=O>C(OCC)(=O)C>[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:40]3[CH2:36][CH2:37][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:39]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25953Cesium fluorideHCID 574768684-((3-Chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-olHCID 86600824HCID 86600824, compound

Product 1

HCID 68523595HCID 68523595, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

4-(3-chloro-2-fluoroanilino)-6-hydroxy-7-methoxyquinazoline (prepared as described in the starting materials used in Example 22; 4.0 g, 12.5 mmol) was mixed with tert-butyl (3S)-3-[(4-nitrophenyl)sulfonyloxy]pyrrolidine-1-carboxylate (4.7 g, 12.6 mmol) and cesium fluoride (5.7 g, 7.5 mmol). Dry N,N-dimethylformamide (60 ml) was then added and the mixture stirred at ambient temperature overnight. The mixture was diluted with ethyl acetate and filtered. The filtrate was washed with water, 50% aqueous brine then brine, dried over Na2SO4, filtered and evaporated. The residue was purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (98/2). The fractions containing the expected product were combined and evaporated to give 4-(3-chloro-2-fluoroanilino)-6-[(3R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yloxy]-7-methoxyquinazoline as a dry foam (2.35 g, 38%); 1H NMR Spectrum: (DMSO d6) 1.39 (s, 9H); 2.10-2.30 (m, 2H); 3.35-3.50 (m, 3H); 3.64-3.71 (m, 1H); 3.92 (s, 3H); 5.12 (m, 1H); 7.21 (s, 1H); 7.23-7.27 (m, 1H); 7.44-7.55 (m, 2H); 7.80 (s, 1H); 8.37 (s, 1H); 9.61 (s, 1H); Mass Spectrum: (M+H)+ 489.

Workup

  1. filtrationfiltered
  2. washThe filtrate was washed with water, 50% aqueous brine
  3. dry with materialbrine, dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography
  7. washeluting with methylene chloride/methanol (saturated with ammonia) (98/2)
  8. additionThe fractions containing the expected product
  9. customevaporated

Sources & evidence

ORD record
ord-b4c382dd7377430590f3547c221cd591
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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