Dichloromethane → N-Demethylivabradine

HRID 423130ノート

反応式

HRID 423130 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C@@H:7]([CH2:13][NH:14][C:15](=N)[CH2:16][CH2:17][N:18]1[C:24](=[O:25])[CH2:23][C:22]3[CH:26]=[C:27]([O:32][CH3:33])[C:28]([O:30][CH3:31])=[CH:29][C:21]=3[CH2:20][CH2:19]1)[CH2:6]2.[BH4-].[BH4-].[BH4-].[BH4-].[Na+].[Na+].[Na+].[Na+].[OH-].[Na+].ClCCl>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C@@H:7]([CH2:13][NH:14][CH2:15][CH2:16][CH2:17][N:18]1[C:24](=[O:25])[CH2:23][C:22]3[CH:26]=[C:27]([O:32][CH3:33])[C:28]([O:30][CH3:31])=[CH:29][C:21]=3[CH2:20][CH2:19]1)[CH2:6]2

参加物

6

反応物 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 131720822Sodium tetraborohydrideHCID 178486555HCID 178486555、化合物

生成物 1

HCID 10389261N-Demethylivabradine収率 102.9%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
0 °C

実験手順

1 g of the product obtained in Step 1 (containing 47% amidine) is dissolved in 15 mL of methanol; the resulting solution is then cooled to 0° C. and 100 mg (2.61 mmol, 1.2 equivalents) of sodium tetraborohydride are added. Stirring is carried out overnight at ambient temperature, and then 5.3 mL of 20% aqueous sodium hydroxide solution and 20 mL of dichloromethane are added. Vigorous stirring is carried out for 15 minutes. The organic phase is then extracted, washed with water, dried over MgSO4, filtered and then evaporated to dryness. There is obtained 1 g of an oil which is purified by flash chromatography on 100 g of silica (eluant=dichloromethane/ethanol/NH4OH: 90/10/1) to yield 300 mg of expected product in the form of an oil.

後処理

  1. stirringVigorous stirring
  2. waitis carried out for 15 minutes
  3. extractionThe organic phase is then extracted
  4. washwashed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated to dryness

出典と根拠

ORDレコード
ord-1d825601e6d547cea99d23ed41b5d6e8
出典データセット
uspto-grants-2012_01
特許番号
US08101747B2

反応ノート

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