Sodium hydride → 7-Fluoroquinazolin-4-amine

HRID 2244049Notes

Reaction equation

HRID 2244049 reaction equation
F[C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C(O)(=O)C.[CH:15](N)=[NH:16].[H-].[Na+].C([O-])(O)=O.[Na+].CC([N:28](C)C)=O>>[F:10][C:8]1[CH:9]=[C:2]2[C:3]([C:4]([NH2:28])=[N:5][CH:15]=[N:16]2)=[CH:6][CH:7]=1

Participants

6

Reactant 5

HCID 24758Sodium hydrideHCID 31374DimethylacetamideHCID 775452,4-DifluorobenzonitrileHCID 160693Formamidine acetateHCID 516892Sodium Bicarbonate

Product 1

HCID 468357077-Fluoroquinazolin-4-amineYield 25%

Conditions

Temperature
120 °C

Procedure

A suspension of 2,4-difluorobenzonitrile (1 g, 7.17 mmol), formamidine acetate (2.98 g, 28.68 mmol), and NaH (60% suspension in mineral oil, 2.29 g, 57.36 mmol) in dimethylacetamide (50 mL) is stirred at 120° C. for overnight. The reaction mixture is poured onto a saturated solution of NaHCO3 (100 mL), and the aqueous phase is extracted with EtOAc (3×). The combined organic layers is washed with brine, dried over MgSO4, and evaporated to dryness. Purification of the crude material by column chromatography (10% MeOH in CH2Cl2) affords 7-Fluoro-quinazolin-4-ylamine (0.2874 g, 25%). LC/MS m/z=164 [M+H]+.

Workup

  1. extractionthe aqueous phase is extracted with EtOAc (3×)
  2. washThe combined organic layers is washed with brine
  3. dry with materialdried over MgSO4
  4. customevaporated to dryness
  5. customPurification of the crude material by column chromatography (10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-d4820b27e8e54831aa886aa16ad4e81b
Source dataset
uspto-grants-2010_03
Patent number
US07678803B2

Reaction notes

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