Toluene → (S)-{1-[7-(3,4-difluorophenyl)-3-(4-ethoxyphenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-2-yl)methanol

HRID 872094Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 872094
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]3[N:15]=[C:16]([CH3:19])[C:17](I)=[C:13]3[N:12]=[C:11]([N:20]3[CH2:24][CH2:23][CH2:22][C@H:21]3[CH2:25][OH:26])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].[CH2:27]([O:29][C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)[CH3:28].C1(C)C=CC=CC=1.C([O-])(O)=O.[Na+]>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.C(O)C>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]3[N:15]=[C:16]([CH3:19])[C:17]([C:33]4[CH:34]=[CH:35][C:30]([O:29][CH2:27][CH3:28])=[CH:31][CH:32]=4)=[C:13]3[N:12]=[C:11]([N:20]3[CH2:24][CH2:23][CH2:22][C@H:21]3[CH2:25][OH:26])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 516892Sodium BicarbonateHCID 27343514-Ethoxyphenylboronic acidHCID 68026319(S)-(1-(7-(3,4-difluorophenyl)-3-iodo-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-2-yl)methanol

Produkt 1

HCID 56932644(S)-{1-[7-(3,4-difluorophenyl)-3-(4-ethoxyphenyl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-2-yl)methanolAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

(S)-(1-(7-(3,4-Difluorophenyl)-3-iodo-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-2-yl)methanol (27 mg), 4-ethoxyphenylboronic acid (16 mg) and tetrakis(triphenylphosphine)palladium (10 mg) are added to toluene (8 mL), ethanol (3 mL) and 1 N NaHCO3 aqueous solution (1.5 mL) and stirred at 85° C. for 6 hours under argon atmosphere. After cooling to room temperature, the reaction solvent is removed by distillation under reduced pressure. The remainder is extracted with ethyl acetate and water. The organic layer is washed with brine and dehydrated with anhydrous MgSO4. The dehydrated organic layer is distilled under reduced pressure, concentrated and purified by column chromatography to yield the target compound (20 mg).

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. customthe reaction solvent is removed by distillation under reduced pressure
  3. extractionThe remainder is extracted with ethyl acetate and water
  4. washThe organic layer is washed with brine
  5. distillationThe dehydrated organic layer is distilled under reduced pressure
  6. concentrationconcentrated
  7. custompurified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-190c35a266874ea09325dab17886b4e4
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08975264B2

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