2-morpholin-4-ylethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-isobenzofuran-5-yl)-4-methyl-hex-4-enoate hydrochloride Struktur

2-morpholin-4-ylethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-isobenzofuran-5-yl)-4-methyl-hex-4-enoate hydrochloride

Bezeichnung:2-morpholin-4-ylethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-isobenzofuran-5-yl)-4-methyl-hex-4-enoate hydrochloride

CAS-Nr116680-01-4

Englisch Name:2-morpholin-4-ylethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-isobenzofuran-5-yl)-4-methyl-hex-4-enoate hydrochloride

CBNumberCB91564362

SummenformelC23H32ClNO7

Molgewicht0

MOL-Datei116680-01-4.mol

2-morpholin-4-ylethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-isobenzofuran-5-yl)-4-methyl-hex-4-enoate hydrochloride physikalisch-chemischer Eigenschaften

Schmelzpunkt	154-155 °C
storage temp.	Store at -20°C
Löslichkeit	>83.3mg/mL in DMSO
Aggregatzustand	Powder

Gefahreninformationscode (GHS)

2-morpholin-4-ylethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-isobenzofuran-5-yl)-4-methyl-hex-4-enoate hydrochloride Chemische Eigenschaften,Einsatz,Produktion Methoden

Originator
CellCept,Pharmacia,Italy
Verwenden
Transplantation (immunosuppressant).
Manufacturing Process
The synthesis of Mycophenolic acid (Canonica L. Et al., Tetrahedron Letters, 1971, N 28, p.2691-2692)
By condensation of sodium diethylmalonate and 3-methylpent-3-en-2-on in ethanol was obtained 2,3-dimethyl-4,6-dioxocyclohexanecarboxilic acid ethyl ester, which was aromatised to 4,6-dihydroxy-2,3-dimethylbenzoic acid ethyl ester (melting point 115-116°C). By treatment with diazomethane or with CH3I and K2CO3 this compound was transformed into 2,4-dimethoxy-5,6- dimethylbenzoic acid ethyl ester (melting point 62-63°C). The hydrolysis of the ester group furnished the 2,4-dimethoxy-5,6-dimethylbenzoic acid (melting point 208-210°C), which was converted into the amide: carbamic acid 3-methoxy-4,5,6-trimethylphenyl ester (melting point 225-229°C). Treatment of the amide with t-butylhypochlorite in methylene dichloride yielded the corresponding N-chloroamide which was photolysed to the intermediate iminolactone and was immediately hydrolized to 5,7-dimethoxy- 4-methyl-3H-isobenzofuran-1-one.
This compound with hydriodic acid in acetic acid in the presence of red phosphorous at reflux yielded 5,7-dihydroxy-4-methyl-3H-isobenzofuran-1- one. Condensation of 6-bromo-4-methylhex-4-enoic acid methyl ester and 5,7-dihydroxy-4-methyl-3H-isobenzofuran-1-one with silver oxide in dioxane at room temperature yielded 6-(4,6-dihydroxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoic acid methyl ester (36% yield). At last, monomethylation with diazomethane yield 6-(4-hydroxy-6-methoxy-7- methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methylhex-4-enoic acid methyl ester, which was hydrolysed with aqueous sodium hydroxide to 6-(4- hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4- methylhex-4-enoic acid (Mycophenolic acid).
Mycophenolic acid may be obtained by the fermentation broth of Pennicillium brevicompactum. The synthesis of Mycophenolate mofetil (Patent U.S. 4,753,935). The mixture of Mycophenolic acid (32.0 g), thionyl chloride (25.0 ml) and DMF (0.3 ml) in dichloromethane (250 ml) was stirred at room temperature for 3 hours, after which the volatile components were removed under vacuum to afford mycophenolic acid chloride as an oil. The mycophenolic acid chloride oil was dissolved in dichloromethane (50.0 ml) and added to the chilled solution of morpholinoethanol (30.5 ml) in dichloromethane (250 ml). After stirring for 90 min at 4°C, the reaction mixture was washed with water and then with aqueous sodium bicarbonate. The organic solution was dried with sodium sulfate and evaporated to yield Mycophenolate mofetil: morpholinoethyl E-6-(1,3-dihydro-4-hydroxy-6- methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate (melting point 93-94°C).
The product (38.0 g) was dissolved in isopropanol (200 ml) and the solution was added to a solution of hydrogen chloride (10.0 g) in isopropanol (150 ml). The hydrochloride of Mycophenolate mofetil was collected by filtration and dried under vacuum (melting point 154-155°C).
Trademarks
Cellcept (Roche).
Therapeutic Function
Antiarthritic, Immunosuppressive

2-morpholin-4-ylethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-isobenzofuran-5-yl)-4-methyl-hex-4-enoate hydrochloride Upstream-Materialien And Downstream Produkte

2-morpholin-4-ylethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-isobenzofuran-5-yl)-4-methyl-hex-4-enoate hydrochloride Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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