Acetone → 2-([N-(2-methoxyethyl)-N-methylamino)ethoxy)quinazoline hydrochloride

HRID 2182569ノート

反応式

HRID 2182569 の反応式
[CH2:1]([N:3]([CH2:6][CH3:7])[CH2:4][CH3:5])C.C[O:9][CH2:10]CBr.[Cl:13]C1C=CC(N[C:19]2[C:28]3[C:23](=[CH:24][C:25](OCCNC)=[C:26](OC)[CH:27]=3)[N:22]=[CH:21][N:20]=2)=C(F)C=1.CC(C)=[O:41]>>[ClH:13].[CH3:10][O:9][CH2:5][CH2:4][N:3]([CH2:6][CH2:7][O:41][C:21]1[N:20]=[CH:19][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=1)[CH3:1]

参加物

5

反応物 4

HCID 180Acetone2 回HCID 8471TriethylamineHCID 809722-Bromoethyl methyl etherHCID 224781924-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-methylaminoethoxy)quinazoline

生成物 1

HCID 867597412-([N-(2-methoxyethyl)-N-methylamino)ethoxy)quinazoline hydrochloride収率 16%

反応条件

温度
50 °C

実験手順

Triethylamine (44 μl, 0.32 mmol) and then a solution of 2-bromoethyl methyl ether (40 mg, 0.29 mmol) in acetone (0.5 ml) was added dropwise to a solution of 4{4-chloro-2-fluoroanilino)-6-methoxy-7-(2-methylaminoethoxy)quinazoline (100 mg, 0.26 mmol) in acetone (2.5 ml) heated at 50° C. under nitrogen. The mixture was stirred for 7 hours at 50° C., the mixture was allowed to cool and partitioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried (MgSO4) and the volatiles removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (92/8). The purified product was dissolved in methylene chloride, insolubles were removed by filtration and 2.2M ethereal hydrogen chloride (0.5 ml) was added to the filtrate. The volatiles were removed by evaporation and the residue was triturated with ether, collected by filtration and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)6-methoxy-7-(2-([N-(2-methoxyethyl)-N-methylamino)ethoxy)quinazoline hydrochloride (22 mg, 16%).

後処理

  1. temperatureto cool
  2. custompartitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. customthe volatiles removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol (92/8)
  9. dissolutionThe purified product was dissolved in methylene chloride
  10. custominsolubles were removed by filtration and 2.2M ethereal hydrogen chloride (0.5 ml)
  11. additionwas added to the filtrate
  12. customThe volatiles were removed by evaporation
  13. customthe residue was triturated with ether
  14. filtrationcollected by filtration
  15. customdried under vacuum

出典と根拠

ORDレコード
ord-f87f21a0781641ac81a366326d6e2239
出典データセット
uspto-grants-2005_05
特許番号
US06897210B2

反応ノート

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