4-Chloro-6,7-bis(2-methoxyethoxy)quinazoline → HCID 71503222, compound

HRID 2038148Notes

Reaction equation

HRID 2038148 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[C:9]([O:12][CH2:13][CH2:14][O:15][CH3:16])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[C:22]([C:24]1[CH:25]=[CH:26][C:27]([F:31])=[C:28]([CH:30]=1)[NH2:29])#[CH:23]>C(O)(C)C>[C:22]([C:24]1[CH:25]=[CH:26][C:27]([F:31])=[C:28]([NH:29][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[C:9]([O:12][CH2:13][CH2:14][O:15][CH3:16])[CH:10]=3)[N:5]=[CH:4][N:3]=2)[CH:30]=1)#[CH:23]

Participants

4

Reactant 2

HCID 112899424-Chloro-6,7-bis(2-methoxyethoxy)quinazolineHCID 451588205-Ethynyl-2-fluoroaniline

Product 1

HCID 71503222HCID 71503222, compoundYield 63.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

4-Chloro-6,7-bis(2-methoxyethoxy)quinazoline (140 mg, 0.447 mmol) and 5-ethynyl-2-fluoroaniline (66 mg, 0.489 mmol) were reacted in refluxing isopropanol (3 mL) overnight under an atmosphere of N2. The solvent was removed by rotary evaporation and the residue was dissolved in CHCl3 and then treated with saturated aqueous NaHCO3. The organic layer was separated and washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was chromatographed on silica using 40% acetone/CH2Cl2 to provide 116 mg of the pure title product as its free base. This oil was dissolved in a minimum volume of CHCl3, diluted with several volumes of ether and titrated with 1M HCl in ether to precipitate the title product as a white solid (99 mg; 54%; LC-MS: m/z=412.1664, m/z(calc)=412.1667).

Workup

  1. customThe solvent was removed by rotary evaporation
  2. dissolutionthe residue was dissolved in CHCl3
  3. additiontreated with saturated aqueous NaHCO3
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was chromatographed on silica using 40% acetone/CH2Cl2

Sources & evidence

ORD record
ord-226c4e3c5e05425cb67f43f6926ff395
Source dataset
uspto-grants-2013_11
Patent number
US08575339B2

Reaction notes

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