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

HRID 279324

反応式

HRID 279324 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.[Br:31][C:32]1[CH:33]=[CH:34][C:35]([O:40][CH2:41][CH3:42])=[C:36]([CH:39]=1)[CH:37]=O.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]=[C:32]([Br:31])[CH:33]=[CH:34][C:35]=2[O:40][CH2:41][CH3:42])[CH2:23][CH2:24]1)=[O:16])=[O:12]

参加物

6

反応物 4

HCID 176Acetic AcidHCID 1449015-Bromo-2-ethoxybenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 184262024-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine

生成物 1

HCID 5089104-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(5-bromo-2-ethoxybenzyl)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), 5-bromo-2-ethoxybenzaldehyde (0.15 mmol), methanol (1.2 mL), and acetic acid (0.030 mL) was added NaBH3CN (0.25 mmol) in methanol (0.50 mL). The reaction mixture was stirred at 50° C. for 13 h. The mixture was cooled to room temperature, loaded onto Varian™ SCX column, and washed with CH3OH (5 mL×3). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated. To the resulting material were added dichloromethane (1 mL) and trifluoroacetic acid (TFA) (0.50 mL) and the solution was stirred at room temperature for 10 min. The reaction mixture was concentrated, and 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. Preparative TLC (SiO2, ethyl acetate/methanol=10/1) gave 4-[{N-(2-amino-4,5-difluorobenzoyl)glycyl}aminomethyl]-1-(5-bromo-2-ethoxybenzyl)piperidine (Compound No. 2052) (10.2 mg, 38%): The purity was determined by RPLC/MS (96%); ESI/MS m/e 539.2 (M++H, C24H29BrF2N4O3).

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with CH3OH (5 mL×3)
  3. washProduct was eluted off
  4. concentrationconcentrated
  5. additionTo the resulting material were added dichloromethane (1 mL) and trifluoroacetic acid (TFA) (0.50 mL)
  6. stirringthe solution was stirred at room temperature for 10 min
  7. concentrationThe reaction mixture was concentrated
  8. dissolutionthe residue was dissolved in methanol
  9. washwashed with CH3OH (5 mL×2)
  10. washProduct was eluted off
  11. concentrationconcentrated

出典と根拠

ORDレコード
ord-b999fcc9697e417ea71b96dd66618cd6
出典データセット
uspto-grants-2002_03
特許番号
US06362177B1

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