Triethylamine → Quinazoline hydrochloride

HRID 2182568ノート

反応式

HRID 2182568 の反応式
CS([Cl:5])(=O)=O.ClC1C=CC(N[C:12]2[C:21]3[C:16](=[CH:17][C:18](OCCCNC)=[C:19](OC)[CH:20]=3)[N:15]=[CH:14][N:13]=2)=C(F)C=1.C(N(CC)CC)C>C(Cl)Cl>[ClH:5].[N:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:12]=[N:13][CH:14]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 224782074-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(3-methylaminopropoxy)quinazoline

生成物 1

HCID 21186983Quinazoline hydrochloride収率 185.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Methanesulphonyl chloride (35 μl, 0.46 mmol) was added dropwise to a solution of 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-methylaminopropoxy)quinazoline (170 mg, 0.43 mmol) and triethylamine (67 μl, 0.48 mmol) in methylene chloride (3 ml). The mixture was stirred for 5 hours at ambient temperature the volatiles was removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and then brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography on silica eluting with methylene chloride/acetonitrile/methanol (70/28/2). The purified product was dissolved in a mixture of methylene chloride/methanol (1/1) and 2M ethereal hydrogen chloride (1 ml) was added. The volatiles were removed by evaporation and the residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6- methoxy-7-(E-methyl-N-methylsulphonyl]amino)propoxy)quinazoline hydrochloride (133 mg, 61%).

後処理

  1. customwas removed by evaporation
  2. customthe residue was partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materialbrine, dried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe residue was purified by column chromatography on silica eluting with methylene chloride/acetonitrile/methanol (70/28/2)
  8. dissolutionThe purified product was dissolved in a mixture of methylene chloride/methanol (1/1) and 2M ethereal hydrogen chloride (1 ml)
  9. additionwas added
  10. customThe volatiles were removed by evaporation
  11. customthe residue was triturated with ether
  12. filtrationcollected by filtration
  13. washwashed with ether
  14. customdried under vacuum

出典と根拠

ORDレコード
ord-376847b48bbd4d139a828026319be001
出典データセット
uspto-grants-2005_05
特許番号
US06897210B2

反応ノート

読み込み中…