Potassium Hydroxide → {1-[(5-Chloro-2,4-dimethoxy-phenylcarbamoyl)-methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}-acetic acid

HRID 472724Notes

Reaction equation

HRID 472724 reaction equation
C[O:2][C:3](=[O:32])[CH2:4][N:5]1[C:14](=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH2:16][C:17](=[O:30])[NH:18][C:19]2[CH:24]=[C:23]([Cl:25])[C:22]([O:26][CH3:27])=[CH:21][C:20]=2[O:28][CH3:29])[C:6]1=[O:31].[OH-].[K+]>CO.O>[Cl:25][C:23]1[C:22]([O:26][CH3:27])=[CH:21][C:20]([O:28][CH3:29])=[C:19]([NH:18][C:17]([CH2:16][N:7]2[C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:14](=[O:15])[N:5]([CH2:4][C:3]([OH:32])=[O:2])[C:6]2=[O:31])=[O:30])[CH:24]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 68588223{1-[(5-chloro-2,4-dimethoxy-phenylcarbamoyl)-methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}-acetic acid methyl ester2×

Product 1

HCID 24896589{1-[(5-Chloro-2,4-dimethoxy-phenylcarbamoyl)-methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}-acetic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A white suspension of {1-[(5-chloro-2,4-dimethoxy-phenylcarbamoyl)-methyl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}-acetic acid methyl ester (Intermediate B) (10 mg) in MeOH (300 μL) is treated with 5 M KOH (200 μL). The white suspension is left to stir at RT overnight. The reaction mixture is diluted with water to give a thick white precipitate which is filtered-off, washed with water and vacuum dried. The aqueous phase is acidified to pH 4 with dilute HCl followed by extraction with EtOAc (3×). The organic phase is dried over Na2SO4, filtered and concentrated in vacuo to give the title compound as off-white solid. This is taken up in a minimal amount of DMF and purified further by reverse phase column chromatography (Isolute™ C18: 0-100% MeCN in water—0.1% TFA) to afford the title compound, [M+H]+ 448.

Workup

  1. waitThe white suspension is left
  2. customto give a thick white precipitate which
  3. washwashed with water and vacuum
  4. customdried
  5. extractionfollowed by extraction with EtOAc (3×)
  6. dry with materialThe organic phase is dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-13d653fa5303495eb33525b7bd1d5d55
Source dataset
uspto-grants-2014_01
Patent number
US08633211B2

Reaction notes

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