Acetic Acid → 4-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(3,4-diethoxybenzyl)piperidine

HRID 279325

反応式

HRID 279325 の反応式
C(OC([NH:8][C:9]1[CH:28]=[C:27]([F:29])[C:26]([F:30])=[CH:25][C:10]=1[C:11]([NH:13][CH2:14][C:15]([NH:17][CH2:18][CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)=[O:16])=[O:12])=O)(C)(C)C.[CH2:31]([O:33][C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][C:41]=1[O:42][CH2:43][CH3:44])[CH:37]=O)[CH3:32].C(O)(=O)C.[BH3-]C#N.[Na+]>CO>[NH2:8][C:9]1[CH:28]=[C:27]([F:29])[C:26]([F:30])=[CH:25][C:10]=1[C:11]([NH:13][CH2:14][C:15]([NH:17][CH2:18][CH:19]1[CH2:20][CH2:21][N:22]([CH2:37][C:36]2[CH:39]=[CH:40][C:41]([O:42][CH2:43][CH3:44])=[C:34]([O:33][CH2:31][CH3:32])[CH:35]=2)[CH2:23][CH2:24]1)=[O:16])=[O:12]

参加物

6

反応物 4

HCID 176Acetic AcidHCID 748473,4-DiethoxybenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 184262024-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine

生成物 1

HCID 184262144-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(3,4-diethoxybenzyl)piperidine

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

反応条件

温度
50 °C

実験手順

To a mixture of 4-[{N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl}aminomethyl]piperidine (0.050 mmol), 3,4-diethoxybenzaldehyde (0.15 mmol), methanol (1.2 mL), and acetic acid (0.050 mL) was added NaBH3CN (0.25 mmol) in methanol (0.50 mL). The reaction mixture was stirred at 50° C. overnight. The mixture was cooled to room temperature, loaded onto Varian™ SCX column, and washed with CH3OH (5 mL×2). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated. To the resulting material were added dichloromethane (2 mL) and phenyl isocyanate (0.10 mL) and the solution was stirred at room temperature for 1 h, loaded onto Varian™ SCX column, and washed with CH3OH (5 mL×2). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated. The residue was dissolved in methanol (0.25 mL) and 4 N HCl in dioxane (0.125 mL) was added. The solution was stirred at room temperature overnight and concentrated. The residue was dissolved in methanol, loaded onto Varian™ SCX column, and washed with CH3OH (5 mL×2). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated to afford 4-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(3,4-diethoxybenzyl)piperidine (Compound No. 2065) (21.2 mg, 84%): The purity was determined by RPLC/MS (97%); ESI/MS m/e 505.2 (M++H, C26H34F2N4O4).

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with CH3OH (5 mL×2)
  3. washProduct was eluted off
  4. concentrationconcentrated
  5. additionTo the resulting material were added dichloromethane (2 mL) and phenyl isocyanate (0.10 mL)
  6. stirringthe solution was stirred at room temperature for 1 h
  7. washwashed with CH3OH (5 mL×2)
  8. washProduct was eluted off
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in methanol (0.25 mL)
  11. addition4 N HCl in dioxane (0.125 mL) was added
  12. stirringThe solution was stirred at room temperature overnight
  13. concentrationconcentrated
  14. dissolutionThe residue was dissolved in methanol
  15. washwashed with CH3OH (5 mL×2)
  16. washProduct was eluted off
  17. concentrationconcentrated

出典と根拠

ORDレコード
ord-fb8fb4addae1454b8f8e181ff8a087a7
出典データセット
uspto-grants-2002_03
特許番号
US06362177B1

関連ノート

読み込み中…