Sodium hydride → 5-Hydroxy-7-methoxy-3-pivaloyloxymethyl-quinazolin-4-one

HRID 749187Notes

Reaction equation

HRID 749187 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([OH:16])[C:8]2[C:9]([OH:15])=[N:10][CH:11]=[N:12][C:13]=2[CH:14]=1.[C:17]([O:23][CH2:24]Cl)(=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19]>CN(C)C=O>[C:17]([O:23][CH2:24][N:10]1[C:9](=[O:15])[C:8]2[C:13](=[CH:14][C:5]([O:4][CH3:3])=[CH:6][C:7]=2[OH:16])[N:12]=[CH:11]1)(=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19]

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 87885Chloromethyl pivalate2×HCID 178493338HCID 178493338, compound

Product 1

HCID 119745575-Hydroxy-7-methoxy-3-pivaloyloxymethyl-quinazolin-4-oneYield 41.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60 mg, 1.49 mmol) was added portionwise over 5 minutes to 7-methoxyquinazoline-4,5-diol (260 mg, 1.35 mmol) in dimethylformamide (2 ml) at 0° C. Chloromethyl pivalate (200 μl, 1.36 mmol) was added dropwise over 15 minutes to give a clear orange solution. The reaction mixture was allowed to warm to ambient temperature and stirred for a further 18 hours. Incomplete reaction was seen by tlc, therefore the reaction was cooled to 0° C. and sodium hydride (10 mg, 0.25 mmol) was added followed by chloromethyl pivalate (26 μl, 6.18 mmol). The reaction was complete after stirring for 1 hour at ambient temperature. The reaction mixture was concentrated in vacuo and purified by chromatography on silica gel, eluting with 2-10% methanol in dichloromethane, to yield (5-hydroxy-7-methoxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate (170 mg, 41% yield) as a cream solid:

Workup

  1. customto give a clear orange solution
  2. customIncomplete reaction
  3. temperaturethe reaction was cooled to 0° C.
  4. stirringafter stirring for 1 hour at ambient temperature
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. custompurified by chromatography on silica gel
  7. washeluting with 2-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-dc368bcab2fa4a2cbe984a6ad92f653a
Source dataset
uspto-grants-2008_07
Patent number
US07402585B2

Reaction notes

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