4-Chloro-6,7-bis(2-methoxyethoxy)quinazoline → [6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-4-fluoro-phenyl)-amine Hydrochloride

HRID 1288872Notes

Reaction equation

HRID 1288872 reaction equation
[Cl:1][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]=[C:26]([CH:28]=[CH:29][C:30]=1[F:31])[NH2:27])#[CH:23]>C(O)(C)C>[ClH:1].[CH3:16][O:15][CH2:14][CH2:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:17][CH2:18][CH2:19][O:20][CH3:21])[N:5]=[CH:4][N:3]=[C:2]2[NH:27][C:26]1[CH:28]=[CH:29][C:30]([F:31])=[C:24]([C:22]#[CH:23])[CH:25]=1

Participants

4

Reactant 2

HCID 112899424-Chloro-6,7-bis(2-methoxyethoxy)quinazolineHCID 126873623-Ethynyl-4-fluoroaniline

Product 1

HCID 18925041[6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-4-fluoro-phenyl)-amine HydrochlorideYield 58.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

4-Chloro-6,7-bis-(2-methoxy-ethoxy)-quinazoline (140 mg, 0.446 mmol) and 3-ethynyl-4-fluoroaniline (66 mg, 0.452 mmol) were reacted in refluxing isopropanol (3 mL) under an atmosphere of N2 for 16 hours. The solvent was removed in vacuo and the residue was partitioned between CHCl3 and saturated aqueous NaHCO3. The organic extracts were 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; 50%; M.P. 170°-190° C. (dec); LC-MS: 412 (MH+); anal. RP18-HPLC RT: 4.33 min.).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was partitioned between CHCl3 and saturated aqueous NaHCO3
  3. washThe organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was chromatographed on silica using 40% acetone/CH2Cl2

Sources & evidence

ORD record
ord-53f13431dfde46f183a3054d0ebc6776
Source dataset
uspto-grants-1998_05
Patent number
US05747498

Reaction notes

Loading…