9-Cyclohexyl-2-alkoxy-9H-adenine process
AssigneeMead Johnson & Company
InventorDavis L. Temple, Jr.
Life of this patent
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Abstract
A process for preparing 9-cyclohexyl-2-alkoxy-9H-adenine derivatives such as 9-cyclohexyl-2-n-propoxy-9H-adenine from 7-amino-5-(methylthio)[1,2,5]oxadiazolo[3,4-d]pyrimidine and 7-amino-5-(methylthio)[1,2,5]thiadiazolo[3,4-d]pyrimidine is described. Other aspects of the invention are directed to novel intermediates such as the compound 4-amino-6-(cyclohexylamino)-5-(formylamino)-2-(methylthio)pyrimidine.
Claims3
A process for preparing 9-cyclohexyl-2-alkoxy-9H-adenine derivatives of Formula I ##STR20## which comprises the consecutive steps of:
- (1) reacting a diazolo[3,4-d]pyrimidine of Formula II wherein X is oxygen or sulfur ##STR21## with 1 to 2 equivalents of cyclohexylamine in an inert reaction solvent at a temperature ranging from 20.degree.-130.degree. to produce the diazolo[3,4-d]pyrimidine of Formula III wherein X is oxygen or sulfur;
- ##STR22## (2) reductively formylating III in 50-100% formic acid employing, when X is oxygen, catalytic hydrogenation with palladium-on-carbon catalyst or when X is sulfur, Raney nickel, to produce the formylated compound of Formula IV;
- ##STR23## (3) cyclizing IV with alkali metal hydroxide to produce the adenine derivative of Formula V;
- ##STR24## (4) oxidizing V in an inert solvant to produce sulfone VI;
- ##STR25## (5) displacing the methylsulfone radical of VI with an alkali metal alkoxide of the formula RO-alk wherein alk represents sodium or potassium and R is 1 to 6 carbon atoms inclusive in an inert reaction solvant to produce a 2-alkoxy-9-cyclohexyladenine of Formula I.
A process for preparing 6-amino-9-cyclohexyl-2-(n-propoxy)purine which comprises the consecutive steps of:
- reductively formylating diazolo[3,4-d]pyrimidine of Formula IIIa ##STR26## in 85-98% formic acid with palladium-on-carbon catalyst to produce the formylated compound of Formula IV;
- ##STR27## cyclizing IV by heating with aqueous sodium hydroxide solution to produce the adenine derivative of Formula V;
- ##STR28## oxidizing V with meta-chloroperbenzoic acid in acetic acid to produce the sulfone of Formula VI;
- ##STR29## displacing the methylsulfone radical of VI with sodium n-propoxide in n-propanol to produce 6-amino-9-cyclohexyl-2-(n-propoxy)purine.
Dependencies are inferred from the claim text.