Reaktion #80914

Reaktionsgleichung

2,4-diamino-6-cyano-5-methylquinazoline

3,4,5-trimethoxyaniline

hydrogen

→

2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyphenylamino)methyl]quinazoline

Ausbeute 27.1%

Lösungsmittel

water

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationAfter this time the reaction mixture was filtered
2. 2
   workup.ADDITIONThe filter cake was slurried with a boiling mixture of 15 mL of water and 35 mL of acetic acid
3. 3
   Filtrationwas then filtered
4. 4
   FiltrationAfter this time the reaction mixture was filtered
5. 5
   Einengenconcentrated under reduced pressure to a residual oil
6. 6
   WaschenElution
7. 7
   Einengenconcentrated under reduced pressure to a residual solid
8. 8
   SonstigeThe solid was recrystallized from water

Vorschrift

A mixture of 1.1 grams (0.005 mole) of 2,4-diamino-6-cyano-5-methylquinazoline, 4.6 grams (0.025 mole) 3,4,5-trimethoxyaniline and 2.0 grams (catalyst) of Raney nickel (50% slurry in water) in 30 mL of water and 70 mL of acetic acid was hydrogenated at 50 psi of hydrogen for 6 hours using a Parr hydrogenator. After this time the reaction mixture was filtered. The filter cake was slurried with a boiling mixture of 15 mL of water and 35 mL of acetic acid and was then filtered. The filtrates were combined and subjected to thin layer chromatography (TLC). The TLC analysis indicated that a small amount of the starting quinazoline remained unreacted. The filtrate was combined with 1.0 gram of Raney nickel and the mixture was again hydrogenated for an additional 1.5 hours using the Parr hydrogenator. After this time the reaction mixture was filtered and concentrated under reduced pressure to a residual oil. The residual oil was subjected to column chromatography on silica gel. Elution was accomplished initially using 25% N,N-dimethylformamide in ethyl acetate and, finally 40% N,N-dimethylformamide in ethyl acetate. The product-containing fractions were combined and concentrated under reduced pressure to a residual solid. The solid was recrystallized from water, yielding 0.5 gram of 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyphenylamino)methyl]quinazoline, mp 95°-210° C. The NMR analysis was consistent with the proposed structure; however, it indicated that the compound was a complex with acetic acid and water. NOTE: The compound of Example 14 is known in the literature as Trimetrexate®, for use in treatments of certain kinds of cancers. [J. Med. Chem., 26, 1753-1760 (1983)]

Quelle