N-(3-Aminopropyl)morpholine → 4-(4-chloro-2-fluoroanilino)-7-methoxy-6-(N-[3-morpholinopropyl]carbamoyl)quinoline

HRID 393666ノート

反応式

HRID 393666 の反応式
[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][CH2:9][NH2:10])[CH2:3][CH2:2]1.[C:11]([C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:23]=1[O:24][CH3:25])[N:20]=[CH:19][CH:18]=[C:17]2[NH:26][C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=1[F:34])(O)=[O:12].Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([NH:26][C:17]2[C:16]3[C:21](=[CH:22][C:23]([O:24][CH3:25])=[C:14]([C:11](=[O:12])[NH:10][CH2:9][CH2:8][CH2:7][N:4]4[CH2:5][CH2:6][O:1][CH2:2][CH2:3]4)[CH:15]=3)[N:20]=[CH:19][CH:18]=2)=[C:28]([F:34])[CH:29]=1

参加物

5

反応物 3

HCID 61055N-(3-Aminopropyl)morpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 226466206-Carboxy-4-(4-chloro-2-fluoroanilino)-7-methoxyquinoline

生成物 1

HCID 226466504-(4-chloro-2-fluoroanilino)-7-methoxy-6-(N-[3-morpholinopropyl]carbamoyl)quinoline収率 40.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

3-Morpholinopropylamine (290 mg, 2 mmol) was added to a solution of 6-carboxy-4-(4-chloro-2-fluoroanilino)-7-methoxyquinoline (200 mg, 0.5 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (191 mg, 1 mmol) and 1-hydroybenzotriazole hydrate (135 mg, 1 mmol) in DMF (15 ml). The mixture was stirred at ambient temperature for 2 hours. The solution was partitioned between water (100 ml) and methylene chloride. The organic layer was washed with brine and dried by passing through phase separating paper. The solvent was removed by evaporation and the crude product was purified by flash chromatography eluting with methylene chloride/methanol (99/1 increasing to 90/10). The pure fractions were combined and the solvent was removed by evaporation. The remaining oil was dissolved in methanol and an ethereal solution of hydrogen chloride was added. The solvent was removed by evaporation and the solid was dried overnight in a vacuum 1 oven at 40° C. to give 4-(4-chloro-2-fluoroanilino)-7-methoxy-6-(N-[3-morpholinopropyl]carbamoyl)quinoline (95 mg, 33%).

後処理

  1. customThe solution was partitioned between water (100 ml) and methylene chloride
  2. washThe organic layer was washed with brine
  3. customdried
  4. customseparating paper
  5. customThe solvent was removed by evaporation
  6. customthe crude product was purified by flash chromatography
  7. washeluting with methylene chloride/methanol (99/1 increasing to 90/10)
  8. customthe solvent was removed by evaporation
  9. dissolutionThe remaining oil was dissolved in methanol
  10. additionan ethereal solution of hydrogen chloride was added
  11. customThe solvent was removed by evaporation
  12. customthe solid was dried overnight in a vacuum 1 oven at 40° C.

出典と根拠

ORDレコード
ord-146d9be88f774321a78d9eb25529aa82
出典データセット
uspto-grants-2004_10
特許番号
US06809097B1

反応ノート

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