Piperidine → Ether hydrochloride

HRID 849406Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 849406
[C:1]([N:8]1[CH:12]=[CH:11]N=[CH:9]1)(N1[CH:7]=[CH:6]N=C1)=[O:2].[ClH:13].Cl.[NH:15]1[CH:19]=[C:18]([CH2:20][N:21]2[C:27]3[CH:28]=[C:29]([NH2:32])[CH:30]=[CH:31][C:26]=3[CH2:25][N:24]([C:33]([C:35]3[C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[CH:38]=[CH:37][CH:36]=3)=[O:34])[CH2:23][CH2:22]2)[N:17]=[CH:16]1.[CH2:45](N(CC)CC)[CH3:46].N1CCCCC1>C(Cl)Cl.C([O-])(O)=O.[Na+].C(Cl)(Cl)Cl>[ClH:13].[ClH:13].[NH:15]1[CH:19]=[C:18]([CH2:20][N:21]2[C:27]3[CH:28]=[C:29]([NH:32][C:1]([N:8]4[CH2:9][CH2:46][CH2:45][CH2:11][CH2:12]4)=[O:2])[CH:30]=[CH:31][C:26]=3[CH2:25][N:24]([C:33]([C:35]3[C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[CH:38]=[CH:37][CH:36]=3)=[O:34])[CH2:23][CH2:22]2)[N:17]=[CH:16]1.[ClH:13].[CH3:6][CH2:7][O:34][CH2:33][CH3:35]

Komponenten

9

Edukt 4

HCID 8082PiperidineHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 1784786502,3,4,5-Tetrahydro-1-(1H-imidazol-4-ylmethyl)-4-(1-naphthalenylcarbonyl)-8-amino-1H-1,4-benzodiazepine, dihydrochloride

Produkt 2

HCID 10953452Ether hydrochlorideHCID 178478887N-[2,3,4,5-Tetrahydro-1-(1H-imidazol-4-ylmethyl)-4-(1-naphthalenylcarbonyl)-1H-1,4-benzodiazepin-8-yl]-1-piperidinecarboxamide, dihydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6212ChloroformLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

Carbonyidiimidazole (0.045 g, 0.137 mmol), was added to a solution of Example 26 (0.050 g, 0.125 mmol), and triethylamine (0.038 mL, 0.275 mmol) in dry methylene chloride (1 mL) at rt under argon. After stirring for 2 hr, piperidine (0.013 mL, 0.13 mmol) was added. After stirring for 15 hr, the reaction was diluted with NaHCO3 and CHCl3. The organic layer was washed with NaHCO3, water, and brine (1×3 mL each), dried over MgSO4, filtered and concentrated. The product was purified by reverse phase HPLC with a gradient of 40-90% aquous methanol with 0.1% TFA and the HCl salt was formed by treatment with 1M HCl/ether to afford Example 247 (0.006 g, 10%).

Aufarbeitung

  1. stirringAfter stirring for 15 hr
  2. washThe organic layer was washed with NaHCO3, water, and brine (1×3 mL each)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe product was purified by reverse phase HPLC with a gradient of 40-90% aquous methanol with 0.1% TFA

Quellen und Nachweise

ORD-Eintrag
ord-2139a2414ebb49b38fba161beabdfbc8
Quelldatensatz
uspto-grants-2000_01
Patentnummer
US06011029

Notizen zur Reaktion

Wird geladen…