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Potassium Carbonate → 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4-(1H-indol-4-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 2405324
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Reaktionsgleichung

Reaktionsgleichung von HRID 2405324
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][C@@H:14]3[CH2:18][CH2:17][N:16]([C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[CH2:15]3)=[N:11][NH:10][C:9]2=[O:24])=[CH:4][CH:3]=1.[NH:25]1[C:33]2[C:28](=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[CH:21]1([C:19]([N:16]2[CH2:17][CH2:18][C@@H:14]([CH2:13][C:12]3[N:8]([C:5]4[CH:6]=[CH:7][C:2]([C:29]5[CH:30]=[CH:31][CH:32]=[C:33]6[C:28]=5[CH:27]=[CH:26][NH:25]6)=[CH:3][CH:4]=4)[C:9](=[O:24])[NH:10][N:11]=3)[CH2:15]2)=[O:20])[CH2:23][CH2:22]1
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Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 27631731H-Indole-4-boronic acidHCID 673755254-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

Produkt 1

HCID 533734105-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4-(1H-indol-4-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-oneAusbeute 50,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A solution of 4-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (0.256 mmol) in dioxane (2 mL) was treated with 1H-indol-4-ylboronic acid (0.386 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (10.4 mg), and 2M aq potassium carbonate (0.511 mmol). The reaction mixture was purged with nitrogen, sealed, and stirred at 100° C. overnight. The reaction mixture was cooled to room temperature and was diluted with water (50 mL). The aqueous layer was acidified to pH ˜4 using 1N aq HCl and was extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The brown residue was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 20-40% acetonitrile w/0.1% TFA/water w/0.1% TFA). The combined product fractions were neutralized with the addition of saturated aq sodium bicarbonate, concentrated under reduced pressure, and extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Further purification of the resulting solid by flash chromatography (0-7% methanol/dichloromethane) gave the title compound as a white amorphous solid (55 mg, 48% yield). MS(ES)+ m/e 428.0 [M+H]+.

Aufarbeitung

  1. customThe reaction mixture was purged with nitrogen
  2. customsealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additionwas diluted with water (50 mL)
  5. extractionwas extracted with dichloromethane
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe brown residue was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 20-40% acetonitrile w/0.1% TFA/water w/0.1% TFA)
  10. additionThe combined product fractions were neutralized with the addition of saturated aq sodium bicarbonate
  11. concentrationconcentrated under reduced pressure
  12. extractionextracted with dichloromethane
  13. dry with materialThe combined organic layers were dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customFurther purification of the resulting solid by flash chromatography (0-7% methanol/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-890579981a5344f3b513c3a24a4da35c
Quelldatensatz
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08802864B2

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