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 1869081ノート

反応式

HRID 1869081 の反応式
[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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

実験手順

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.).

後処理

  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

出典と根拠

ORDレコード
ord-804dfd488d454e8b9cb654ea5d8ba8fd
出典データセット
uspto-grants-2009_12
特許番号
USRE041065E1

反応ノート

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