Sodium Hydroxide → HCID 59371216, compound

HRID 1948956Notes

Reaction equation

HRID 1948956 reaction equation
[OH-].[Na+].[Cl:3][C:4]1[C:5]([F:34])=[C:6]([CH:31]=[CH:32][CH:33]=1)[NH:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([O:29][CH3:30])=[C:15]([O:18][C@H:19]3[CH2:23][N:22]([CH3:24])[CH:21]([C:25]([O:27]C)=[O:26])[CH2:20]3)[CH:16]=2)[N:11]=[CH:10][N:9]=1>CO>[Cl:3][C:4]1[C:5]([F:34])=[C:6]([CH:31]=[CH:32][CH:33]=1)[NH:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([O:29][CH3:30])=[C:15]([O:18][C@H:19]3[CH2:23][N:22]([CH3:24])[CH:21]([C:25]([OH:27])=[O:26])[CH2:20]3)[CH:16]=2)[N:11]=[CH:10][N:9]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59371213HCID 59371213, compound

Product 1

HCID 59371216HCID 59371216, compoundYield 64.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2M NaOH (1 ml, 2 mmol) was added to a stirred solution of 4-(3-chloro-2-fluoroanilino)-6-[(2RS,4R)-1-methyl-2-(methoxycarbonyl)pyrrolidin-4-yloxy]-7-methoxyquinazoline (250 mg, 0.54 mmol) in methanol (5 ml) and the mixture stirred at room temperature for 18 hours. The reaction mixture was evaporated and the residues re-dissolved in water (50 ml). This was then washed with ethyl acetate (25 ml) and the aqueous phase evaporated to dryness and azeotroped with toluene. The residues were triturated with methylene chloride/methanol (9/1) (25 ml), filtered and the liquors evaporated to give 4-(3-chloro-2-fluoroanilino)-6-[(2RS,4R)-1-methyl-2-carboxypyrrolidin-4-yloxy]-7-methoxyquinazoline as a white foam (155 mg); Mass Spectrum: (M+H)+ 447,

Workup

  1. customThe reaction mixture was evaporated
  2. dissolutionthe residues re-dissolved in water (50 ml)
  3. washThis was then washed with ethyl acetate (25 ml)
  4. customthe aqueous phase evaporated to dryness
  5. customazeotroped with toluene
  6. customThe residues were triturated with methylene chloride/methanol (9/1) (25 ml)
  7. filtrationfiltered
  8. customthe liquors evaporated

Sources & evidence

ORD record
ord-481dfd5ed8a54ba083124e34cd54c400
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

Loading…