Imidazole → (3-Ethynyl-phenyl)-[7-(2-imidazol-1-yl-ethoxy)-6-(2-methoxy-ethoxy)quinazolin-4-yl]-amine dihydrochloride

HRID 1288880Notes

Reaction equation

HRID 1288880 reaction equation
[ClH:1].[Cl:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]#[CH:24])[CH:18]=3)=[N:11][CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH2:26][CH2:27][O:28][CH3:29].[NH:30]1[CH:34]=[CH:33][N:32]=[CH:31]1>CN(C=O)C>[ClH:2].[ClH:1].[C:23]([C:19]1[CH:18]=[C:17]([NH:16][C:10]2[C:9]3[C:14](=[CH:15][C:6]([O:5][CH2:4][CH2:3][N:30]4[CH:34]=[CH:33][N:32]=[CH:31]4)=[C:7]([O:25][CH2:26][CH2:27][O:28][CH3:29])[CH:8]=3)[N:13]=[CH:12][N:11]=2)[CH:22]=[CH:21][CH:20]=1)#[CH:24]

Participants

4

Reactant 2

HCID 795ImidazoleHCID 18925049[7-(2-Chloro-ethoxy)-6-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-phenyl)-amine Hydrochloride

Product 1

HCID 18925100(3-Ethynyl-phenyl)-[7-(2-imidazol-1-yl-ethoxy)-6-(2-methoxy-ethoxy)quinazolin-4-yl]-amine dihydrochlorideYield 66.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The title product from Example 34 (110 mg, 0.253 mmol) in DMF (2 mL) was treated with imidazole (172 mg, 2.53 mmol) at 110° C. for 48 hours. The reaction mixture 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 (119 mg) was chromatographed on silica using 10% methanol/CH2Cl2 to provide 85 mg of pure title product as its free base. This white solid was dissolved in a minimum volume of CHCl3, and titrated with 2 equivalents of 1M HCl in ether to precipitate the title product as a white solid (95 mg; 75%; M.P. 220°-227° C. (dec); LC-MS: 430 (MH+); anal. RP18-HPLC RT: 3.75 min.).

Workup

  1. customThe reaction mixture was partitioned between CHCl3 and saturated aqueous NaHCO3
  2. washThe organic extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product (119 mg) was chromatographed on silica using 10% methanol/CH2Cl2

Sources & evidence

ORD record
ord-7422f844cce743f2aa5e73d7fd81da2d
Source dataset
uspto-grants-1998_05
Patent number
US05747498

Reaction notes

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