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Sodium Iodide → 6-Butyl-8-({1-[3-(methylsulfonyl)propyl]-4-piperidinyl}oxy)quinoline, dihydrochloride salt

HRID 1363020
ノート
印刷プレビュー

反応式

HRID 1363020 の反応式
[CH2:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([O:15][CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)[CH2:2][CH2:3][CH3:4].[I-].[Na+].C(=O)(O)[O-].[Na+].[CH3:29][S:30]([CH2:33][CH2:34][CH2:35]Br)(=[O:32])=[O:31].CS(CCC[Cl:44])(=O)=O>CN(C=O)C.CO>[ClH:44].[ClH:44].[CH2:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([O:15][CH:16]3[CH2:17][CH2:18][N:19]([CH2:35][CH2:34][CH2:33][S:30]([CH3:29])(=[O:32])=[O:31])[CH2:20][CH2:21]3)[CH:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)[CH2:2][CH2:3][CH3:4]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 5238Sodium IodideHCID 516892Sodium BicarbonateHCID 138750421-Chloro-3-methanesulfonylpropane2 回HCID 518920821-Bromo-3-methanesulfonylpropaneHCID 579260486-Butyl-8-(4-piperidinyloxy)quinoline2 回

生成物 1

HCID 131728651
6-Butyl-8-({1-[3-(methylsulfonyl)propyl]-4-piperidinyl}oxy)quinoline, dihydrochloride salt
収率 18%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
150 °C

実験手順

A mixture of 6-butyl-8-(4-piperidinyloxy)quinoline (for example, as prepared for Intermediate 4) (80 mg, 0.28 mmol), sodium iodide (30 mg, 0.2 mmol) and sodium bicarbonate (110 mg, 1.3 mmol) in DMF (2 ml) was treated with a solution of mixture of 3-bromopropyl methyl sulfone and 3-chloropropyl methyl sulfone (for example, as prepared for Intermediate 19) (124 mg) in DMF (0.5 ml) and the mixture was heated at 150° C. for 15 min in a Smith Creator™ microwave oven. The reaction mixture was applied to an SCX-2 cartridge (10 g), preconditioned with methanol, and eluted with methanol, followed by 10% aqueous 0.88 s.g. ammonia in methanol. The ammoniacal fractions were combined and concentrated in vacuo and the residue (126 mg) was purified by MDAP. Appropriate fractions were combined and concentrated in vacuo and the residue (30 mg) was applied to an SCX-2 cartridge (5 g), pre-conditioned with methanol and eluted with methanol, followed by 10% aqueous 0.88 s.g. ammonia in methanol. The ammoniacal fractions were combined and concentrated in vacuo to give the free base of the title compound (21 mg, 18%): This was treated with 1.25 M hydrogen chloride solution in methanol (0.15 ml) and the solution was evaporated in vacuo to give the title compound (22 mg, 89%): LCMS RT=2.49 min, ES+ve m/z 405 (M+H)+.

後処理

  1. washeluted with methanol
  2. customfollowed by 10% aqueous 0.88 s
  3. concentrationconcentrated in vacuo
  4. customthe residue (126 mg) was purified by MDAP
  5. concentrationconcentrated in vacuo
  6. washeluted with methanol
  7. customfollowed by 10% aqueous 0.88 s
  8. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-60a9677521dc4467879e6d15d97e4813
出典データセット
uspto-grants-2011_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07884114B2

反応ノート

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