Phosphorus pentachloride → 4,6-Dichloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidine

HRID 650797

Reaktionsgleichung

Reaktionsgleichung von HRID 650797
C(C1N=CC=CN=1)#N.[ClH:9].N1C=CC=NC=1C(N)=N.N.[NH4+].[Cl-:21].C[O-].[Na+].CO.C[O-].[Na+].COC1C=CC=CC=1OC(C(OCC)=O)C(OCC)=O.[CH3:50][O:51][C:52]1[CH:72]=[CH:71][CH:70]=[CH:69][C:53]=1[O:54][CH:55]1[C:60](=O)[NH:59][CH:58]([C:62]2[N:67]=[CH:66][CH:65]=[CH:64][N:63]=2)[NH:57][C:56]1=O.C(N(C(C)C)CC)(C)C.P(Cl)(Cl)(Cl)(Cl)Cl>>[Cl:9][C:60]1[C:55]([O:54][C:53]2[CH:69]=[CH:70][CH:71]=[CH:72][C:52]=2[O:51][CH3:50])=[C:56]([Cl:21])[N:57]=[C:58]([C:62]2[N:67]=[CH:66][CH:65]=[CH:64][N:63]=2)[N:59]=1

Komponenten

10

Edukt 9

HCID 24819Phosphorus pentachlorideHCID 81531DiisopropylethylamineHCID 27579792-CyanopyrimidineHCID 10942334Sodium MethoxideHCID 11140560Diethyl (2-methoxyphenoxy)propanedioateHCID 219795675-(2-Methoxyphenoxy)-2-(pyrimidin-2-yl)-tetrahydropyrimidin-4,6-dioneHCID 219837312-Amidinopyrimidine hydrochlorideHCID 23694274Sodium methanolate methanolHCID 86743336Ammonia ammonium chloride

Produkt 1

HCID 105457064,6-Dichloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidine

Versuchsvorschrift

The process of the present invention is especially useful for the preparation of 4-tert.butyl-N-6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(pyrimidine-2-yl)-pyrimidine-4-yl-benzenesulphonamide (bosentan). For the preparation of this compound 2-cyanopyrimidine is prepared as described above and converted into pyrimidin-2-carboxamidine hydrochloride by means of NH3/NH4Cl in a sodium methanolate/methanol solution. This compound is converted in the presence of sodium methanolate with diethyl (o-methoxy-phenoxy-malonate) into rac-5-(2-methoxy-phenoxy)-2-pyrimidin-2-yl-tetrahydro-pyrimidin-4,6-dione. The obtained product is reacted with N,N-diisopropyl-N-ethylamine and phosphorus pentachloride to give 4,6-dichloro-5-(2-methoxy-phenoxy)-2,2′-bipyrimidine. This substance is then reacted with p-tert.butylbenzenesulphonamide to give 4-tert.butyl-N-6-chloro-5-[2-(2-methoxy-phenoxy)-2-(pyrimidin-2-yl)-pyrimidin-4-yl]-benzenesulphonamide and further reacted with sodium ethylene glycolate to give 4-tert.butyl-N-6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(pyrimidin-2-yl)-pyrimidin-4-yl-benzenesulphonamide (bosentan).

Aufarbeitung

  1. customis prepared

Quellen und Nachweise

ORD-Eintrag
ord-241e0788f69d4e2f8b251b0f174be803
Quelldatensatz
uspto-grants-2001_08
Patentnummer
US06274734B1

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