Processes for the production of α-difluoromethyl ornithine (DFMO)
View Patent ↗Provided are processes and synthetic intermediates useful for the preparation of α-difluoromethylornithine (DFMO) having the formula
1. A process for the preparation of a compound of the formula
the process comprising:
providing an intermediate compound having fluorine and a nitrile moiety; and
selectively reducing said nitrile moiety to form an amine moiety,
wherein said intermediate compound is:
wherein R 1 is linear or branched C 1 to C 4 alkyl and Z is
(i) —NH 2 or
(ii) a moiety selected from the group consisting of
wherein R 2 is hydrogen, linear or branched C 1 to C 4 alkyl or aryl, and
wherein R 4 is linear or branched C 1 to C 4 alkyl, alkoxy, or aryl.
2. The process of claim 1 , wherein Z is
further comprising hydrolyzing the intermediate compound to produce a compound having one of the following formulas
3. The process of claim 2 further comprising hydrolyzing the compound of formula 7, 9, or 10 to form the compound of formula 1.
4. The process of claim 1 , wherein the intermediate compound is ethyl 2-benzylideneamino-2-difluoromethyl-4-cyanobutanote, ethyl 2-(diphenylmethylene)amino-2-difluoromethyl-4-cyanobutanoate, ethyl 2-amino-2-difluoromethyl-4-cyanobutanoate, ethyl 2-acetylamino-2-difluoromethyl-4-cyanobutanote, or a salt thereof.
5. A compound of the formula
wherein R 1 is linear or branched C 1 to C 4 alkyl; and
wherein R 5 is:
(a)
wherein R 2 is hydrogen, linear or branched C 1 to C 4 alkyl or aryl;
(b) NH 2 ; or
(c)
wherein R 4 is linear or branched C 1 to C 4 alkyl, alkoxy or aryl.
6. The compound of claim 5 wherein R 1 is selected from the group consisting of methyl, ethyl, and t-butyl.