Dichloromethane → HCID 86647917, Verbindung

HRID 1970945Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1970945
Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C:10]2[CH:11]=[CH:12][C:13](B(O)O)=[N:14][CH:15]=2)[CH:7]=[CH:8][CH:9]=1.[Cl:19][C:20]1[CH:25]=[C:24](Cl)[N:23]=[C:22]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)[N:21]=1.C(Cl)Cl>COCCOC.C(=O)([O-])[O-].[Na+].[Na+].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]>[Cl:19][C:20]1[CH:25]=[C:24]([C:12]2[CH:13]=[N:14][CH:15]=[C:10]([C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([O:3][CH3:2])[CH:5]=3)[CH:11]=2)[N:23]=[C:22]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)[N:21]=1

Komponenten

7

Edukt 3

HCID 6344DichloromethaneHCID 120574654,6-dichloro-2-(2-pyridinyl)pyrimidineHCID 67331136HCID 67331136, Verbindung

Produkt 1

HCID 86647917HCID 86647917, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 80711,2-DimethoxyethaneLösungsmittelHCID 10340Sodium CarbonateLösungsmittel

Versuchsvorschrift

A solution of 5-(3-methoxy-phenyl)-pyridine boronic acid hydrochloride (Int. D) (1 eq, 59 mg) in DME (1 ml) and 2M sodium carbonate (0.4 ml) is treated with 4,6-dichloro-2-pyridin-2-yl-pyrimidine (Int. C) (1 eq, 50 mg) and placed under an atmosphere of argon. PdCl2(dppf).DCM (0.1 eq. 16 mg) is added and the reaction mixture is heated using microwave radiation at 90° C. for 1 h. After cooling to room temperature, the mixture is partitioned between EtOAc/water and the organic portion is separated, washed with brine, dried (MgSO4) and concentrated in vacuo. The crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-100% acetonitrile in water—0.1% TFA) and the appropriate fractions are combined and concentrated in vacuo. The residue is loaded onto a SCX-2 cartridge eluting with MeOH followed by 2M NH3 in MeOH. The methanolic ammonia fractions are concentrated in vacuo and dried under vacuum overnight to afford the title compound [M+H]+=375/377.

Aufarbeitung

  1. temperaturethe reaction mixture is heated
  2. customat 90° C.
  3. customfor 1 h
  4. customthe mixture is partitioned between EtOAc/water
  5. customthe organic portion is separated
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-100% acetonitrile in water—0.1% TFA)
  10. concentrationconcentrated in vacuo
  11. washeluting with MeOH
  12. concentrationThe methanolic ammonia fractions are concentrated in vacuo
  13. customdried under vacuum overnight

Quellen und Nachweise

ORD-Eintrag
ord-ec8f9c9cd6dc480e92e99b2aff1d680f
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08431578B2

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