Water → (S)-benzyl 2-(8-amino-1-(4-(pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate

HRID 928296Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 928296
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@@H:12]3[CH2:16][CH2:15][CH2:14][N:13]3[C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])=[N:9][C:10]=2Br)[CH:5]=[CH:6][N:7]=1.[N:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[NH:33][C:34]([C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1)=[O:35].C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C@@H:12]3[CH2:16][CH2:15][CH2:14][N:13]3[C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])=[N:9][C:10]=2[C:39]2[CH:38]=[CH:37][C:36]([C:34](=[O:35])[NH:33][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][N:27]=3)=[CH:41][CH:40]=2)[CH:5]=[CH:6][N:7]=1

Komponenten

7

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 441195394-(Pyridin-2-yl)aminocarbonylphenylboronic acidHCID 71233875(S)-Benzyl 2-(8-amino-1-bromoimidazo(1,5-a)pyrazin-3-yl)pyrrolidine-1-carboxylate

Produkt 1

HCID 71233862(S)-benzyl 2-(8-amino-1-(4-(pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylateAusbeute 77 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

(S)-benzyl 2-(8-amino-1-bromoimidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate (0.237 mmol, 98.5 mg) and 4-(pyridin-2-yl-aminocarbonyl)benzeneboronic acid (0.260 mmol, 63.0 mg) were suspended in a mixture of 2N aqueous potassium carbonate solution (2.37 mmol, 1.18 mL) and dioxane (2.96 mL). Nitrogen was bubbled through the mixture, followed by the addition of 1,1′-bis(diphenylphosphino)ferrocene palladium (ii) chloride (0.059 mmol, 47.8 mg). The reaction mixture was heated for 20 minutes at 140° C. in the microwave. Water was added to the reaction mixture, followed by an extraction with ethyl acetate (2×). The combined organic layer was washed with brine, dried over magnesium sulfate and evaporated. The product was purified using silica gel and dichloromethane/methanol=9/1 v/v % as eluent to afford 97.1 mg of (S)-benzyl 2-(8-amino-1-(4-(pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate (77%).

Aufarbeitung

  1. customNitrogen was bubbled through the mixture
  2. extractionfollowed by an extraction with ethyl acetate (2×)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated
  6. customThe product was purified

Quellen und Nachweise

ORD-Eintrag
ord-54c5f334c3924f3da75e50ccadc823de
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09290504B2

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