Potassium Carbonate → 1-[2-(4-{2-[2-(3,5-dimethoxyphenyl)ethyl]-5H-pyrrolo[2,3-b]pyrazin-6-yl}-1H-pyrazol-1-yl)ethyl]piperidin-4-ol

HRID 1052263Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1052263
[N:1]1([CH2:7][CH2:8]O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=[O:32].[CH3:41][O:42][C:43]1[CH:44]=[C:45]([CH2:51][CH2:52][C:53]2[N:54]=[C:55]3[CH:61]=[C:60]([C:62]4[CH:63]=[N:64][NH:65][CH:66]=4)[N:59](S(C4C=CC=CC=4)(=O)=O)[C:56]3=[N:57][CH:58]=2)[CH:46]=[C:47]([O:49][CH3:50])[CH:48]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1>[CH3:41][O:42][C:43]1[CH:44]=[C:45]([CH2:51][CH2:52][C:53]2[N:54]=[C:55]3[CH:61]=[C:60]([C:62]4[CH:66]=[N:65][N:64]([CH2:8][CH2:7][N:1]5[CH2:2][CH2:3][CH:4]([OH:32])[CH2:5][CH2:6]5)[CH:63]=4)[NH:59][C:56]3=[N:57][CH:58]=2)[CH:46]=[C:47]([O:49][CH3:50])[CH:48]=1

Komponenten

7

Edukt 5

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 18232N-PiperidinoethanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 89963624HCID 89963624, Verbindung

Produkt 1

HCID 730565351-[2-(4-{2-[2-(3,5-dimethoxyphenyl)ethyl]-5H-pyrrolo[2,3-b]pyrazin-6-yl}-1H-pyrazol-1-yl)ethyl]piperidin-4-olAusbeute 13,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a stirred solution of 1-piperidineethanol (7.9 mg, 0.0613 mmol) and triphenylphosphine (16.1 mg, 0.0613 mmol) in tetrahydrofuran (1.0 mL), diethyl azodicarboxylate (9.65 μL, 0.0613 mmol) was added at ambient temperature. After 15 minutes, a solution of 2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-6-(1H-pyrazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine (from Example 35, Step 1, 25 mg, 0.0510 mmol) in tetrahydrofuran (0.5 mL) was added. After 16 hours, the reaction was quenched with saturated aqueous NaHCO3, extracted with methylene chloride. The combined organic layers were dried over MgSO4, and then concentrated. The residue was dissolved in methanol (2 mL) and potassium carbonate (14.1 mg, 0.102 mmol) was added. The reaction mixture was then warmed up to 60° C. After 30 minutes, the crude mixture was cooled to ambient temperature and purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min) to give the desired product (3.2 mg) as its TFA salt. LCMS calculated for C26H33N6O3 (M+H)+: m/z=477.3. Found: 477.2.

Aufarbeitung

  1. waitAfter 16 hours
  2. customthe reaction was quenched with saturated aqueous NaHCO3
  3. extractionextracted with methylene chloride
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in methanol (2 mL)
  7. waitAfter 30 minutes
  8. custompurified on RP-HPLC (XBridge C18 column
  9. washeluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min)

Quellen und Nachweise

ORD-Eintrag
ord-039587e520f34430b2cea64bf8e77cbb
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388185B2

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