Potassium Carbonate → HCID 67376212, Verbindung

HRID 2405387Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2405387
[CH:1]1([C:4]([N:6]2[CH2:10][CH2:9][C@@H:8]([CH2:11][C:12]3[N:13]([C:18]4[CH:23]=[CH:22][C:21](B5OC(C)(C)C(C)(C)O5)=[CH:20][C:19]=4[F:33])[C:14](=[O:17])[NH:15][N:16]=3)[CH2:7]2)=[O:5])[CH2:3][CH2:2]1.Br[C:35]1[CH:36]=[CH:37][C:38]2[S:42][CH:41]=[N:40][C:39]=2[CH:43]=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>[S:42]1[C:38]2[CH:37]=[CH:36][C:35]([C:21]3[CH:22]=[CH:23][C:18]([N:13]4[C:12]([CH2:11][C@@H:8]5[CH2:9][CH2:10][N:6]([C:4]([CH:1]6[CH2:3][CH2:2]6)=[O:5])[CH2:7]5)=[N:16][NH:15][C:14]4=[O:17])=[C:19]([F:33])[CH:20]=3)=[CH:43][C:39]=2[N:40]=[CH:41]1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 36101555-BromobenzothiazoleHCID 67376890HCID 67376890, Verbindung

Produkt 1

HCID 67376212HCID 67376212, VerbindungAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A solution of 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (0.230 mmol) in dioxane (1.5 mL) was treated with 5-bromo-1,3-benzothiazole (0.230 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (9 mg), and 2M aq potassium carbonate (0.690 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, treated with Si-Thiol (Silicycle, 20 mg), filtered, and concentrated in vacuo. Silica gel chromatography (0-8% methanol/dichloromethane) and reverse phase HPLC (20-50% acetonitrile w/0.1% TFA/water w/0.1% TFA) were utilized in purifying this compound. The product fractions from the HPLC were combined, adjusted to pH˜5 with the addition of saturated aq sodium bicarbonate, and extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo, providing the title compound as an amorphous off-white solid (39%). MS(ES)+ m/e 464.3 [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. additiontreated with Si-Thiol (Silicycle, 20 mg)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customin purifying this compound
  11. additionadjusted to pH˜5 with the addition of saturated aq sodium bicarbonate
  12. extractionextracted with dichloromethane
  13. dry with materialThe organic layer was dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-c7c48cbaa45340838cd98a8829624df9
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08802864B2

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