Hydrochloric Acid → N-({1-(2-benzyloxycarbonyl-2-methylpropyl)piperidin-4-yl}methyl)-3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-carboxamide

HRID 736425Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 736425
C(N1C2C=CC=CC=2NC1=O)(C)C.C(N(CC)CC)C.ClC(OC1C=CC([N+]([O-])=O)=CC=1)=O.Cl.[CH2:35]([O:42][C:43]([C:45]([CH3:56])([CH3:55])[CH2:46][N:47]1[CH2:52][CH2:51][CH:50]([CH2:53][NH2:54])[CH2:49][CH2:48]1)=[O:44])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[CH:57]([N:60]1[C:64]2[CH:65]=[CH:66][CH:67]=[CH:68][C:63]=2[N:62]([C:69](NCC2CCN(CC3(C(O)=O)CCOCC3)CC2)=[O:70])[C:61]1=[O:89])([CH3:59])[CH3:58].Cl.[OH-].[Na+]>ClCCl.CO>[CH2:35]([O:42][C:43]([C:45]([CH3:56])([CH3:55])[CH2:46][N:47]1[CH2:52][CH2:51][CH:50]([CH2:53][NH:54][C:69]([N:62]2[C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][C:64]=3[N:60]([CH:57]([CH3:58])[CH3:59])[C:61]2=[O:89])=[O:70])[CH2:49][CH2:48]1)=[O:44])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Komponenten

10

Edukt 7

HCID 313Hydrochloric AcidHCID 8471Triethylamine2×HCID 14798Sodium HydroxideHCID 821294-Nitrophenyl chloroformateHCID 16535801-(Propan-2-yl)-1,3-dihydro-2H-benzimidazol-2-oneHCID 117122634-((4-((((3-Isopropyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)carbonyl)amino)methyl)piperidin-1-yl)methyl)tetrahydro-2H-pyran-4-carboxylic acidHCID 685840941-(2-Benzyloxycarbonyl-2-methylpropyl)-4-aminomethylpiperidine hydrochloride

Produkt 1

HCID 68585579N-({1-(2-benzyloxycarbonyl-2-methylpropyl)piperidin-4-yl}methyl)-3-isopropyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-carboxamideAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a stirred mixture of 1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one (J. Med. Chem. 1999, 42, 2870-2880) (411 mg, 2.33 mmol) and triethylamine (1.00 mL, 7.17 mmol) in dichloromethane (20.0 mL) was added 4-nitrophenyl chloroformate (470 mg, 2.33 mmol) at room temperature. The resulting mixture was stirred for 2 h at room temperature. To the mixture was added a suspension of 1-(2-benzyloxycarbonyl-2-methylpropyl)-4-aminomethylpiperidine hydrochloride [prepared from concentration of a mixture of tert-butyl [{1-(2-benzyloxycarbonyl-2-methylpropyl)piperidin-4-yl}methyl]carbamate (step 1 of Example 1) (640 mg, 1.49 mmol) and 10% HCl in MeOH (20.0 mL)] and triethylamine (1.00 mL, 7.17 mmol) in dichloromethane (5.00 mL). The resulting mixture was stirred for 13 h at room temperature and 0.5 M NaOH aq. was added to the mixture. The mixture was extracted with dichloromethane. The extracts were washed with 0.5 M NaOH aq. and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by preparative thin layer chromatography (silica gel, eluting with dichloromethane/methanol (10:1)) to give 508 mg (63%) of the title compound as a pale yellow oil.

Aufarbeitung

  1. additionTo the mixture was added
  2. stirringThe resulting mixture was stirred for 13 h at room temperature
  3. extractionThe mixture was extracted with dichloromethane
  4. washThe extracts were washed with 0.5 M NaOH aq. and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by preparative thin layer chromatography (silica gel, eluting with dichloromethane/methanol (10:1))

Quellen und Nachweise

ORD-Eintrag
ord-3c7ba23e335941e1a9ead078a67b6a05
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07595329B2

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