1-Hydroxybenzotriazole → N-((3S,5S,6R)-6-Methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-yl)-2'-oxo-1'-((2-(trimethylsilyl)ethoxy)methyl)-1',2'-dihydro-3H-spiro[furo[2,3-b]pyridine-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide

HRID 931402Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 931402
[O:1]=[C:2]1[N:10]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C:3]21[O:29][C:21]1=[N:22][CH:23]=[C:24]([C:26]([OH:28])=O)[CH:25]=[C:20]1[CH2:19]2.[NH2:30][C@H:31]1[CH2:36][C@@H:35]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C@@H:34]([CH3:43])[N:33]([CH2:44][C:45]([F:48])([F:47])[F:46])[C:32]1=[O:49].Cl.N[C@H]1C[C@@H](C2C=CC=CC=2)[C@@H](C)N(CC(F)(F)F)C1=O.C(N(CC)C(C)C)(C)C.Cl.C(N=C=NCCCN(C)C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[CH3:43][C@H:34]1[N:33]([CH2:44][C:45]([F:48])([F:46])[F:47])[C:32](=[O:49])[C@@H:31]([NH:30][C:26]([C:24]2[CH:25]=[C:20]3[CH2:19][C:3]4([C:4]5[C:5](=[N:6][CH:7]=[CH:8][CH:9]=5)[N:10]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:17])([CH3:18])[CH3:16])[C:2]4=[O:1])[O:29][C:21]3=[N:22][CH:23]=2)=[O:28])[CH2:36][C@H:35]1[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Komponenten

8

Edukt 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68749751(3S,5S,6R)-3-amino-6-methyl-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-2-one hydrochlorideHCID 68749752(3S,5S,6R)-3-Amino-6-methyl-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-2-oneHCID 900505402'-Oxo-1'-((2-(trimethylsilyl)ethoxy)methyl)-1',2'-dihydro-3H-spiro[furo[2,3-b]pyridine-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxylic acid

Produkt 1

HCID 131735169N-((3S,5S,6R)-6-Methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-3-yl)-2'-oxo-1'-((2-(trimethylsilyl)ethoxy)methyl)-1',2'-dihydro-3H-spiro[furo[2,3-b]pyridine-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of 2′-oxo-1′-((2-(trimethylsilyl)ethoxy)methyl)-1′,2′-dihydro-3H-spiro[furo[2,3-b]pyridine-2,3′-pyrrolo[2,3-b]pyridine]-5-carboxylic acid, (described in Intermediate 5) (0.095 g, 0.23 mmol), (3S,5S,6R)-3-amino-6-methyl-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-2-one, (described in Intermediate 1) (0.098 g, 0.35 mmol), N,N-diisopropylethylamine (0.12 mL, 0.69 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.065 g, 0.35 mmol) and HOBT (0.015 g, 0.12 mmol) in DMF (3 mL) was stirred initially at 0° C. for 15 min, then gradually warmed to 23° C. and stirred for 3 h. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate. The organic layer was dried over sodium sulfate, and concentrated. The residue was purified by flash chromatography on silica gel eluting with 50% ethyl acetate in petroleum ether to give the title compounds as a 1:1 mixture of isomers. MS: m/z=682.5 (M+1).

Aufarbeitung

  1. temperaturegradually warmed to 23° C.
  2. stirringstirred for 3 h
  3. customThe reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel eluting with 50% ethyl acetate in petroleum ether

Quellen und Nachweise

ORD-Eintrag
ord-fc3574ec31384f328832f5a0a2da9470
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09296750B2

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