4-Methylmorpholine → 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-(5-{[(6-ethyl-2-pyridinyl)amino]carbonyl}-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoate

HRID 1396970Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1396970
[CH:1]1([CH2:6][C@H:7]([CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:8]([N:10]2[CH:14]([C:15](O)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.CN1CCOCC1.[CH2:50]([C:52]1[N:57]=[C:56]([NH2:58])[CH:55]=[CH:54][CH:53]=1)[CH3:51]>C(#N)C>[CH:1]1([CH2:6][C@@H:7]([C:8]([N:10]2[CH:14]([C:15]([NH:58][C:56]3[CH:55]=[CH:54][CH:53]=[C:52]([CH2:50][CH3:51])[N:57]=3)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:18][C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:2][CH2:3][CH2:4][CH2:5]1

Komponenten

6

Edukt 4

HCID 79724-MethylmorpholineHCID 890216-Ethylpyridin-2-amineHCID 27340604-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-iumHCID 682877191-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid

Produkt 1

HCID 682879751,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-(5-{[(6-ethyl-2-pyridinyl)amino]carbonyl}-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoateAusbeute 79 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a solution of 1-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid (352 mg, 1.0 mmol) in acetonitrile (10 mL) at 0° C. was added 4-[4,6-bis(methyloxy)-1,3,5-triazin-2-yl]-4-methylmorpholin-4-ium (656 mg, 2.0 mmol) and N-methylmorpholine (0.28 mL, 2.5 mmol). The reaction mixture was stirred for 2 hours. After this time, 6-ethyl-2-pyridinamine (159 mg, 1.3 mmol) was added to the mixture, which was then allowed to warm to room temperature and stirred for 3 hours. The solvent was removed under reduced pressure, and water (5 mL) and DCM (15 mL) were added to the resulting residue. The phases were separated. The aqueous phase was extracted twice with DCM (15 mL), and the combined organic phases were dried over sodium sulfate and concentrated. The crude product residue was purified by Combiflash silica gel chromatography (0-100% EtOAc in hex) to provide 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-(5-{[(6-ethyl-2-pyridinyl)amino]carbonyl}-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoate (359 mg, 0.79 mmol, 79% yield) as a clear oil. MS: 457 ([M+H]+).

Aufarbeitung

  1. stirringstirred for 3 hours
  2. customThe solvent was removed under reduced pressure, and water (5 mL) and DCM (15 mL)
  3. additionwere added to the resulting residue
  4. customThe phases were separated
  5. extractionThe aqueous phase was extracted twice with DCM (15 mL)
  6. dry with materialthe combined organic phases were dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product residue was purified by Combiflash silica gel chromatography (0-100% EtOAc in hex)

Quellen und Nachweise

ORD-Eintrag
ord-c8e86cde5be74d63a582e12f5f973b26
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901119B2

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