Triethylamine → (R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-(4-ethoxycarbonyl methoxy-1,4'-bipiperidinyl-1'-yl)-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 2267265Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2267265
C(N(CC)CC)C.[O:8]=[C:9]1[N:15]([CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C@@H:25]([C:39](O)=[O:40])[CH2:26][C:27]3[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[C:30]([NH2:37])=[C:29]([Cl:38])[CH:28]=3)=[O:23])[CH2:18][CH2:17]2)[CH2:14][CH2:13][C:12]2[CH:42]=[CH:43][CH:44]=[CH:45][C:11]=2[NH:10]1.[CH2:46]([O:48][C:49](=[O:64])[CH2:50][O:51][CH:52]1[CH2:57][CH2:56][N:55]([CH:58]2[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]2)[CH2:54][CH2:53]1)[CH3:47].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C([O-])(O)=O.[Na+]>CN(C=O)C>[O:8]=[C:9]1[N:15]([CH:16]2[CH2:17][CH2:18][N:19]([C:22]([O:24][C@H:25]([CH2:26][C:27]3[CH:32]=[C:31]([C:33]([F:35])([F:36])[F:34])[C:30]([NH2:37])=[C:29]([Cl:38])[CH:28]=3)[C:39]([N:61]3[CH2:60][CH2:59][CH:58]([N:55]4[CH2:56][CH2:57][CH:52]([O:51][CH2:50][C:49]([O:48][CH2:46][CH3:47])=[O:64])[CH2:53][CH2:54]4)[CH2:63][CH2:62]3)=[O:40])=[O:23])[CH2:20][CH2:21]2)[CH2:14][CH2:13][C:12]2[CH:42]=[CH:43][CH:44]=[CH:45][C:11]=2[NH:10]1

Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57807779Ethyl([1,4']bipiperidinyl-4-yloxy)-acetateHCID 58202073(R)-2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Produkt 1

HCID 57807585(R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-(4-ethoxycarbonyl methoxy-1,4'-bipiperidinyl-1'-yl)-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

0.30 mL (2.16 mmol) triethylamine were added to a mixture of 300 mg (0.54 mmol) (R)-2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate (Example 1f), 220 mg (0.64 mmol) ethyl([1,4′]bipiperidinyl-4-yloxy)-acetate (Example A13c) and 200 mg (0.62 mmol) TBTU in 3 mL DMF and the reaction mixture was stirred for 4 h at RT. Ice and saturated NaHCO3 solution were added and the precipitate was filtered off. This was taken up in DCM and a little EtOH and dried over Na2SO4. After elimination of the desiccant and solvent the residue was purified by HPLC; the fractions containing the product were combined and lyophilised.

Aufarbeitung

  1. filtrationthe precipitate was filtered off
  2. dry with materiala little EtOH and dried over Na2SO4
  3. customAfter elimination of the desiccant and solvent the residue was purified by HPLC
  4. additionthe fractions containing the product

Quellen und Nachweise

ORD-Eintrag
ord-d5a9ffe1a1624f38884a7cc5dcbf8136
Quelldatensatz
uspto-grants-2010_12
Patentnummer
US07858622B2

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