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

HRID 1869089Notes

Reaction equation

HRID 1869089 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-bc6bd7a3ee7042358bf57443b5db4558
Source dataset
uspto-grants-2009_12
Patent number
USRE041065E1

Reaction notes

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