2,2,6,6-Tetramethylpiperidine → HCID 86706147, Verbindung

HRID 2176298Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2176298
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([NH:14][C:15]([C@@H:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:27])[C@@H:24]([NH2:26])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1.[C:28]([CH:31]([O:36][C:37](=[O:43])[C:38]([CH3:42])([CH3:41])[CH:39]=[CH2:40])[CH:32]1[CH2:35][O:34][CH2:33]1)(O)=[O:29].CC1(C)CCCC(C)(C)N1.F[P-](F)(F)(F)(F)F.C(C(=NO[C+](N(C)C)N1CCOCC1)C(OCC)=O)#N>CN(C)C=O.ClCCl>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C@H:12]([NH:14][C:15]([C@@H:17]3[CH2:22][CH2:21][CH2:20][N:19]([C:23](=[O:27])[C@@H:24]([NH:26][C:28]([CH:31]([O:36][C:37](=[O:43])[C:38]([CH3:42])([CH3:41])[CH:39]=[CH2:40])[CH:32]4[CH2:35][O:34][CH2:33]4)=[O:29])[CH3:25])[NH:18]3)=[O:16])[CH3:13])=[N:9]2)=[CH:4][CH:3]=1

Komponenten

7

Edukt 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 86706144HCID 86706144, VerbindungHCID 86706146HCID 86706146, VerbindungHCID 178472143HCID 178472143, Verbindung

Produkt 1

HCID 86706147HCID 86706147, VerbindungAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A stirred solution of (S)-1-((S)-2-amino-propionyl)-hexahydro-pyridazine-3-carboxylic acid [(R)-1-(7-bromo-quinolin-2-yl)-ethyl]-amide (141 mg, 0.618 mmol) and 2,2-dimethyl-but-3-enoic acid carboxy-oxetan-3-yl-methyl ester (315 mg, 0.725 mmol) in anhydrous N,N-dimethylformamide (10 mL) was cooled to 0° C. under nitrogen. 2,2,6,6-Tetramethylpiperidine (261 mg, 313 μL, 1.85 mmol) was added, rapidly followed by (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate (371 mg, 0.865 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 15 h. The reaction mixture was diluted with dichloromethane and washed with saturated ammonium chloride solution (2×), saturated sodium bicarbonate solution (2×), the organic layer was filtered through a phase-separator and evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 1:0 to 0:1 to give the title compound (167 mg, 42%) as a yellow/brown foam and as an approximate 1:1 mixture of diastereoisomers. LCMS (m/z) 644.2, 646.1[M+H], Tr=2.63 min.

Aufarbeitung

  1. washwashed with saturated ammonium chloride solution (2×), saturated sodium bicarbonate solution (2×)
  2. filtrationthe organic layer was filtered through a phase-separator
  3. customevaporated
  4. customThe residue was purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-ade14bc13d72466c9b37879833c51c9c
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09062092B2

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