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

HRID 2405316Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2405316
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.[Cl:25][C:26]1[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:27]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[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:28]=[CH:27][C:26]([Cl:25])=[CH:31][C:30]=5[Cl:32])=[CH:3][CH:4]=4)[C:9](=[O:24])[NH:10][N:11]=3)[CH2:15]2)=[O:20])[CH2:23][CH2:22]1

Komponenten

7

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 2734659(2,4-Dichlorophenyl)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 533735535-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-(2',4'-dichloro-4-biphenylyl)-2,4-dihydro-3H-1,2,4-triazol-3-oneAusbeute 22,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittel2×HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A vial was charged with a slurry of 4-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (100 mg, 0.256 mmol), (2,4-dichlorophenyl)boronic acid (98 mg, 0.511 mmol), tetrakis(triphenylphosphine)palladium(0) (29.5 mg, 0.026 mmol) and tripotassium phosphate (217 mg, 1.022 mmol) in ethanol (4.0 mL) and water (4.00 mL) then purged with nitrogen and sealed with a standard teflon septa (crimped aluminum seal). The reaction was heated in an aluminum block at 110° C. for 2 h. The cooled reaction was diluted with ethanol then evaporated under reduced pressure to a yellow residue. The residue was triturated from methanol and the filtered methanol layer was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 20-70% acetonitrile w/0.1% TFA/water w/0.1% TFA). The desired product fractions were combined and evaporated in vacuo to a residue that was recrystallized from hexanes/ethyl acetate to afford the title compound as a white solid (26 mg, 21.8%). MS(ES)+ m/e 457.0, 459.2 [M+H]+, chlorine pattern.

Aufarbeitung

  1. customthen purged with nitrogen
  2. customsealed with a standard teflon
  3. custom(crimped aluminum seal)
  4. customThe cooled reaction
  5. customthen evaporated under reduced pressure to a yellow residue
  6. customThe residue was triturated from methanol
  7. customthe filtered methanol layer was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 20-70% acetonitrile w/0.1% TFA/water w/0.1% TFA)
  8. customevaporated in vacuo to a residue that
  9. customwas recrystallized from hexanes/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-ea9048ca8b3f49328e2664207ec51ddc
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08802864B2

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