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Cesium carbonate → 1-(2-Cyclopropylpyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine

HRID 1662252
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1662252
Br[C:2]1[CH:3]=[C:4]([C:8]2([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([CH:25]4[CH2:27][CH2:26]4)[CH:20]=3)[C:16]3[C:11](=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=3)[C:10]([NH2:18])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[N:28]1[CH:33]=[C:32](B(O)O)[CH:31]=[N:30][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.CCO.O.CCOC(C)=O.[Cl-].[Na+].O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[CH:25]1([C:21]2[CH:20]=[C:19]([C:8]3([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([C:32]5[CH:33]=[N:28][CH:29]=[N:30][CH:31]=5)[CH:3]=4)[C:16]4[C:11](=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=4)[C:10]([NH2:18])=[N:9]3)[CH:24]=[CH:23][N:22]=2)[CH2:27][CH2:26]1
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Komponenten

8

Edukt 3

HCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 593275531-(3-Bromophenyl)-1-(2-cyclopropylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine

Produkt 1

HCID 462020811-(2-Cyclopropylpyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amineAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 53485975
CID 53485975
Katalysator
HCID 8857Ethyl AcetateLösungsmittel
HCID 57417360Sodium chloride; waterLösungsmittel
HCID 86587095Dimethoxyethane ethanol waterLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To a solution of 1-(3-bromophenyl)-1-(2-cyclopropylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine (97 mg, 0.23 mmol) in DME:EtOH:water (6:3:1) (5 mL) was added pyrimidin-5-ylboronic acid (37.0 mg, 0.30 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]-palladium (II) dichloromethane adduct (9.38 mg, 0.01 mmol) and cesium carbonate (225 mg, 0.69 mmol). The vial was sealed and heated in a microwave reactor at 150° C. for 20 minutes. The reaction was diluted with EtOAc and brine, the layers were separated and the aqueous layer was extracted with EtOAc. The organics were combined, dried (Na2SO4), filtered and the solvent was removed under reduced pressure. The crude was purified by preparative HPLC, appropriate fractions combined and the MeOH removed by evaporation. The remaining aqueous phase was basified by addition of sat. aqueous NaHCO3 (pH˜9) and extracted with dichloromethane (×3). The organics were combined, washed once with sat. aqueous NaHCO3, dried (Na2SO4), filtered and evaporated to give 60 mg (62%) of the title compound.

Aufarbeitung

  1. customThe vial was sealed
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure
  7. customThe crude was purified by preparative HPLC, appropriate fractions
  8. customthe MeOH removed by evaporation
  9. additionThe remaining aqueous phase was basified by addition of sat. aqueous NaHCO3 (pH˜9)
  10. extractionextracted with dichloromethane (×3)
  11. washwashed once with sat. aqueous NaHCO3
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-e175f6894d734e34b52fa7bbad214535
Quelldatensatz
uspto-grants-2011_10
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08030500B2

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