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

HRID 525192Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 525192
[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][CH:19]=4)[C:14](=[O:17])[NH:15][N:16]=3)[CH2:7]2)=[O:5])[CH2:3][CH2:2]1.Br[C:34]1[CH:35]=[C:36]([CH:45]=[CH:46][CH:47]=1)[C:37]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:38].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C>[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:19]=[CH:20][C:21]([C:43]5[CH:42]=[CH:41][CH:40]=[C:39]([C:37]([C:36]6[CH:45]=[CH:46][CH:47]=[CH:34][CH:35]=6)=[O:38])[CH:44]=5)=[CH:22][CH:23]=4)[C:14](=[O:17])[NH:15][N:16]=3)[CH2:7]2)=[O:5])[CH2:3][CH2:2]1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 705483-BromobenzophenoneHCID 673756365-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

Produkt 1

HCID 673773895-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[3'-(phenylcarbonyl)-4-biphenylyl]-2,4-dihydro-3H-1,2,4-triazol-3-oneAusbeute 55 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

In a sealed tube, a mixture of 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (179 mg, 0.265 mmol), 3-bromobenzophenone (66 mg, 0.253 mmol), and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (10 mg, 0.012 mmol) in 2M aq potassium carbonate (0.5 mL, 1.00 mmol) and 1,4-dioxane (1.5 mL) was stirred at 100° C. for 1 h. The reaction was cooled to room temperature and the reaction mixture was diluted with ethyl acetate (10 mL). The layers were separated and the aqueous layer was acidified to pH˜5 using 1N aq HCl. The aqueous layer was then extracted with ethyl acetate (20 mL). The organic layers were combined, dried over MgSO4, and concentrated in vacuo. Purification of the residue by silica gel chromatography (0-3% methanol/ethyl acetate) provided the title compound as an ivory solid (68 mg, 55%) after drying in the vacuum oven (70° C.) for 4 days. MS(ES)+ m/e 493.2 [M+H]+.

Aufarbeitung

  1. temperatureThe reaction was cooled to room temperature
  2. customThe layers were separated
  3. extractionThe aqueous layer was then extracted with ethyl acetate (20 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by silica gel chromatography (0-3% methanol/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-876e802e027f4db6a9d67b1f04a6ee4c
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09340529B2

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