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

HRID 133610

반응식

HRID 133610 반응식
[BH3-]C#N.[Na+].C(OC([NH:12][C:13]1[CH:32]=[C:31]([F:33])[C:30]([F:34])=[CH:29][C:14]=1[C:15]([NH:17][CH2:18][C:19]([NH:21][CH2:22][CH:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)=[O:20])=[O:16])=O)(C)(C)C.[CH2:35]([O:37][C:38]1[CH:39]=[C:40]([CH:43]=[CH:44][C:45]=1[O:46][CH2:47][CH3:48])[CH:41]=O)[CH3:36].CO>C(O)(=O)C>[NH2:12][C:13]1[CH:32]=[C:31]([F:33])[C:30]([F:34])=[CH:29][C:14]=1[C:15]([NH:17][CH2:18][C:19]([NH:21][CH2:22][CH:23]1[CH2:24][CH2:25][N:26]([CH2:41][C:40]2[CH:43]=[CH:44][C:45]([O:46][CH2:47][CH3:48])=[C:38]([O:37][CH2:35][CH3:36])[CH:39]=2)[CH2:27][CH2:28]1)=[O:20])=[O:16]

참가 물질

6

반응물 4

HCID 887MethanolHCID 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 176Acetic Acid용매

반응 조건

온도
50 °C

실험 절차

NaBH3CN (0.25 mmol) was added to a mixture of 4-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine (0.050 mmol) with 3,4-diethoxybenzaldehyde (0.15 mol), methanol (1.2 mL) and acetic acid (0.050 mL), and the obtained mixture was stirred at 50° C. overnight, cooled to room temperature, loaded onto a Varian™ SCX column and washed with methanol (5 mL×2). The obtained product was eluted with a 2 M methanol solution of NH3 (5 mL) and concentrated. Dichloromethane (2 mL) and phenyl isocyanate (0.10 mL) were added to the obtained residue, and the resulting mixture was stirred at room temperature for 1 hour, loaded onto a Varian™ SCX column and washed with methanol (5 mL). The obtained product was eluted with a 2 M methanol solution of NH3 (5 mL) and concentrated. The residue was dissolved in methanol (0.25 mL); and a 4 M dioxane solution of HCl (0.125 mL) was added to the resulting solution. The obtained mixture was stirred at room temperature overnight and concentrated. The resulting residue was dissolved in methanol, loaded onto a Varian™ SCX column and washed with methanol (5 mL×2). The obtained crude product was eluted with a 2 M methanol solution of NH3 (5 mL) and concentrated to thereby afford 4-[[N-(2-amino-4,5-difluorobenzoyl)glycyl]aminomethyl]-1-(3,4-diethoxybenzyl)piperidine (Compd. 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. temperaturecooled to room temperature
  2. washwashed with methanol (5 mL×2)
  3. washThe obtained product was eluted with a 2 M methanol solution of NH3 (5 mL)
  4. concentrationconcentrated
  5. additionDichloromethane (2 mL) and phenyl isocyanate (0.10 mL) were added to the obtained residue
  6. stirringthe resulting mixture was stirred at room temperature for 1 hour
  7. washwashed with methanol (5 mL)
  8. washThe obtained product was eluted with a 2 M methanol solution of NH3 (5 mL)
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in methanol (0.25 mL)
  11. additionand a 4 M dioxane solution of HCl (0.125 mL) was added to the resulting solution
  12. stirringThe obtained mixture was stirred at room temperature overnight
  13. concentrationconcentrated
  14. dissolutionThe resulting residue was dissolved in methanol
  15. washwashed with methanol (5 mL×2)
  16. customThe obtained crude product
  17. washwas eluted with a 2 M methanol solution of NH3 (5 mL)
  18. concentrationconcentrated to thereby afford 4-[[N-(2-amino-4,5-difluorobenzoyl)glycyl]aminomethyl]-1-(3,4-diethoxybenzyl)piperidine (Compd. No

출처 및 근거

ORD 기록
ord-6d0bd4d42a754ca78765b1a1ba3b4097
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07390830B1

연결된 노트

불러오는 중…