Morpholine → (3-Ethynyl-phenyl)-[7-(2-methoxy-ethoxy)-6-(2-morpholin-4-yl-ethoxy)-quinazolin-4-yl]-amine Dihydrochloride

HRID 1288882Notes

Reaction equation

HRID 1288882 reaction equation
[ClH:1].[Cl:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[O:16][CH2:17][CH2:18][O:19][CH3:20])[N:12]=[CH:11][N:10]=[C:9]2[NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]#[CH:29])[CH:23]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>CN(C=O)C>[ClH:2].[ClH:1].[C:28]([C:24]1[CH:23]=[C:22]([NH:21][C:9]2[C:8]3[C:13](=[CH:14][C:15]([O:16][CH2:17][CH2:18][O:19][CH3:20])=[C:6]([O:5][CH2:4][CH2:3][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)[CH:7]=3)[N:12]=[CH:11][N:10]=2)[CH:27]=[CH:26][CH:25]=1)#[CH:29]

Participants

4

Reactant 2

HCID 8083MorpholineHCID 189250626-O-Desmethoxyethyl-6-O-chloroethyl Erlotinib Hydrochloride

Product 1

HCID 18925000(3-Ethynyl-phenyl)-[7-(2-methoxy-ethoxy)-6-(2-morpholin-4-yl-ethoxy)-quinazolin-4-yl]-amine DihydrochlorideYield 50.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The title product from Example 30 (107 mg, 0.245 mmol) in DMF (2 mL) was treated with morpholine (214 μL, 2.45 mmol) at 80° C. for 24 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 (168 mg) was chromatographed on silica using 7.5% methanol/CH2Cl2 to provide 65 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 (88 mg; 59%; M.P. 115°-130° C. (dec); LC-MS: 449 (MH+); anal. RP18-HPLC RT: 4.00 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 (168 mg) was chromatographed on silica using 7.5% methanol/CH2Cl2

Sources & evidence

ORD record
ord-0ffa3108547d467a98078218e1097ed1
Source dataset
uspto-grants-1998_05
Patent number
US05747498

Reaction notes

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