Cesium carbonate → (5-(3-Amino-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanol

HRID 1662201Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1662201
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[F:11])[C:4]([C:19]2[CH:20]=[C:21]([CH3:29])[C:22]([O:27][CH3:28])=[C:23]([CH2:25][OH:26])[CH:24]=2)([C:12]2[CH:17]=[CH:16][CH:15]=[C:14](Br)[CH:13]=2)[N:3]=1.[N:30]1[CH:35]=[C:34](B(O)O)[CH:33]=[N:32][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.CCO.O.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]>[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[F:11])[C:4]([C:19]2[CH:20]=[C:21]([CH3:29])[C:22]([O:27][CH3:28])=[C:23]([CH2:25][OH:26])[CH:24]=2)([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:34]3[CH:35]=[N:30][CH:31]=[N:32][CH:33]=3)[CH:13]=2)[N:3]=1

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 58579488(5-(3-Amino-1-(3-bromophenyl)-4-fluoro-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanol

Produkt 1

HCID 58579497(5-(3-Amino-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanolAusbeute 74,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 86587095Dimethoxyethane ethanol waterLösungsmittel

Versuchsvorschrift

(5-(3-Amino-1-(3-bromophenyl)-4-fluoro-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanol (338 mg, 0.74 mmol), pyrimidine-5-boronic acid (110 mg, 0.89 mmol), cesium carbonate (726 mg, 2.23 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (60.6 mg, 0.07 mmol) were dissolved in DME:EtOH:water (6:3:1) (5 mL) and irradiated in a microwave oven for 20 min at 150° C. The solvent was evaporated in vacuo and to the residue was added water, 2 M HCl solution to reach pH˜7, and EtOAc. The organic phase was collected, dried and filtered. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC to give 250 mg (74%) of the title compound.

Aufarbeitung

  1. customirradiated in a microwave oven for 20 min at 150° C
  2. customThe solvent was evaporated in vacuo and to the residue
  3. additionwas added water, 2 M HCl solution
  4. customThe organic phase was collected
  5. customdried
  6. filtrationfiltered
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-0d854741bca347e5980e91958ca2c20d
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08030500B2

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