Nitrogen → Ammonia

HRID 1524192Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1524192
Br[C:2]1[N:7]=[C:6]2[N:8]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([Cl:17])[CH:12]=3)[CH:9]=[N:10][C:5]2=[CH:4][CH:3]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.N#N.[NH2:66][CH:67]1[CH2:72][CH2:71][CH:70]([OH:73])[CH2:69][CH2:68]1.CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH3:7].[Cl:17][C:13]1[CH:12]=[C:11]([N:8]2[C:6]3=[N:7][C:2]([NH:66][CH:67]4[CH2:72][CH2:71][CH:70]([OH:73])[CH2:69][CH2:68]4)=[CH:3][CH:4]=[C:5]3[N:10]=[CH:9]2)[CH:16]=[CH:15][N:14]=1

Komponenten

9

Edukt 5

HCID 947NitrogenHCID 812934-AminocyclohexanolHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 866518705-bromo-3-(2-chloro-pyridin-4-yl)-3-H-imidazo[4,5-b]pyridine2×

Produkt 2

HCID 222AmmoniaHCID 866518694-[3-(2-Chloro-pyridin-4-yl)-3H-imidazo[4,5-b]pyridine-5-ylamino]-cyclohexanol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A mixture comprising 5-bromo-3-(2-chloro-pyridin-4-yl)-3-H-imidazo[4,5-b]pyridine (Intermediate A)(1 eq, 0.323 mmol, 100 mg), BINAP (0.025 mmol, 40 mg) and Pd2(dba)3 (0.0125 mmol, 25 mg) is suspended in dioxane under an inert atmosphere of N2 and heated to 85° C. In a separate flask 4-amino-cyclohexanol (2 eq, 0.647 mmol, 74 mg) and sodium tertbutoxide (2.5 eq, 0.809 mmol, 77 mg) is dissolved in dioxane and warmed to 50° C., before adding to the reaction mixture. The combined mixture was heated for 2 hours. After cooling to room temperature, the mixture is purified by chromatography on silica eluting with 98:2 DCM: ammonia in MeOH to afford the title compound which is used in the next step without further purification; [M+H]+310.

Aufarbeitung

  1. temperaturewarmed to 50° C.
  2. additionbefore adding to the reaction mixture
  3. temperatureThe combined mixture was heated for 2 hours
  4. temperatureAfter cooling to room temperature
  5. customthe mixture is purified by chromatography on silica eluting with 98:2 DCM

Quellen und Nachweise

ORD-Eintrag
ord-3655ddf336a3491fa1fb4684e4496b1e
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09079897B2

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