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

HRID 279325

반응식

HRID 279325 반응식
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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol용매2회

반응 조건

온도
50 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-fb8fb4addae1454b8f8e181ff8a087a7
출처 데이터셋
uspto-grants-2002_03
특허 번호
US06362177B1

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