Hydrochloric Acid → HCID 58010006, Verbindung

HRID 1854434Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1854434
S([N:11]1[C:15]2[N:16]=[CH:17][C:18]3[N:19]([C:20]([C@@H:23]4[CH2:28][CH2:27][CH2:26][N:25](C(OCC5C6C=CC=CC=6C6C5=CC=CC=6)=O)[CH2:24]4)=[CH:21][N:22]=3)[C:14]=2[CH:13]=[CH:12]1)(C1C=CC(C)=CC=1)(=O)=O.[OH-].[Na+].Cl.[C:49]([C:51]1([C:54]([OH:56])=O)[CH2:53][CH2:52]1)#[N:50].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>O1CCOCC1.CN(C=O)C>[CH:13]1[C:14]2[N:19]3[C:20]([C@@H:23]4[CH2:28][CH2:27][CH2:26][N:25]([C:54]([C:51]5([C:49]#[N:50])[CH2:53][CH2:52]5)=[O:56])[CH2:24]4)=[CH:21][N:22]=[C:18]3[CH:17]=[N:16][C:15]=2[NH:11][CH:12]=1

Komponenten

9

Edukt 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 27332591-Cyanocyclopropanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58010039HCID 58010039, Verbindung

Produkt 1

HCID 58010006HCID 58010006, VerbindungAusbeute 9,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 312751,4-DioxaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of (R)-(9H-fluoren-9-yl)methyl 3-(3-tosyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)piperidine-1-carboxylate (0.20 g, 0.32 mmol) in 1,4-dioxane (3 mL) was added aqueous NaOH (2 N, 0.97 mL, 1.9 mmol). The reaction mixture was heated at about 100° C. for about 3 h before it was allowed to cool to ambient temperature. The reaction was neutralized with 4N HCl in 1,4-dioxane (0.5 mL) and was concentrated under reduced pressure. To the residue was added MeCN (25 mL) before it was concentrated under reduced pressure. This procedure was repeated before the addition of 1-cyanocyclopropanecarboxylic acid (0.072 g, 0.65 mmol), HATU (0.111 g, 0.291 mmol) and DMF (2 mL) followed by DIEA (0.170 mL, 0.971 mmol). After stirring at room temperature for about 3 h, the reaction was partitioned between EtOAc (2×50 mL) and aqueous NaHCO3 (50 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude reaction was purified by RP-HPLC (Table 2, Method j). The combined product-containing fractions were concentrated under reduced pressure to remove MeCN and then lyophilized to give (R)-1-(3-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)piperidine-1-carbonyl)cyclopropanecarbonitrile as a white solid (0.010 g, 9%): LC/MS (Table 2, Method a) Rt=1.67 min; MS m/z: 335 (M+H)+.

Aufarbeitung

  1. temperatureto cool to ambient temperature
  2. concentrationwas concentrated under reduced pressure
  3. additionTo the residue was added MeCN (25 mL) before it
  4. concentrationwas concentrated under reduced pressure
  5. customthe reaction was partitioned between EtOAc (2×50 mL) and aqueous NaHCO3 (50 mL)
  6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude reaction
  10. customwas purified by RP-HPLC (Table 2, Method j)
  11. additionThe combined product-containing fractions
  12. concentrationwere concentrated under reduced pressure
  13. customto remove MeCN

Quellen und Nachweise

ORD-Eintrag
ord-b04b691f0e554393b1c5a1e8b4b132d6
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08962629B2

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