Compounds and methods for the treatment or prevention of
View Patent ↗The present invention provides novel compounds represented by formula I: or pharmaceutically acceptable salts thereof useful for treating flaviviridae viral infection.
1. A process for preparing a compound of formula A:
said process comprising the steps of adding:
an enol ether;
an hydride donating agent; and
an organic carboxylic acid;
to a compound of formula B:
wherein,
Y 1 is chosen from a bond, C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl;
Y is chosen from COOR 16 , COCOOR 5 , P(O)OR a OR b , S(O)OR 5 , S(O) 2 OR 5 , tetrazole, CON(R 9 )CH(R 5 )COOR 5 , CONR 10 R 11 , CON(R 9 )—SO 2 —R 5 , CONR 9 OH or halogen, wherein R 9 , R 5 , R 10 and R 11 are each independently chosen from H, C 1-12 alkyl, C 2-12 alkenyl, C 2-12 alkynyl, C 6-14 aryl, C 3-12 heterocycle, C 3-18 heteroaralkyl, C 6-18 aralkyl;
or R 10 and R 11 are taken together with the nitrogen to form a 3 to 10 membered heterocycle;
R a and R b are each independently chosen from H, C 1-12 alkyl, C 2-12 alkenyl, C 2-12 alkynyl, C 6-14 aryl, C 3-12 heterocycle, C 3-18 heteroaralkyl and C 6-18 aralkyl;
or R a and R b are taken together with the oxygens to form a 5 to 10 membered heterocycle;
R 16 is chosen from H, C 1-12 alkyl, C 2-12 alkenyl, C 2-12 alkynyl, C 6-14 aryl, C 3-12 heterocycle, C 3-18 heteroaralkyl and C 6-18 aralkyl;
R 1 is chosen from C 1-12 alkyl, C 2-12 alkenyl, C 2-12 alkynyl, C 6-14 aryl, C 3-12 heterocycle, C 3-18 heteroaralkyl, C 6-18 aralkyl or halogen;
R 2 is chosen from C 1-12 alkyl, C 2-12 alkenyl, C 2-12 alkynyl, C 3-12 heterocycle, C 3-18 heteroaralkyl, or C 6-18 aralkyl;
R 3 is chosen from H, C 1-12 alkyl, C 2-12 alkenyl, C 2-12 alkynyl, C 6-14 aryl, C 3-12 heterocycle, C 3-18 heteroaralkyl or C 6-18 aralkyl;
Z is chosen from H, halogen, C 1-6 alkyl.
2. The process according to claim 1 , wherein said enol ether comprises
a) an alkylated or silylated enolate of an aldehyde, ketone, or ester; or
b) 2-methoxypropene.
3. The process according to claim 2 , wherein said enol ether is 2-methoxypropene.
4. The process according to claim 1 , wherein said hydride donating agent is selected from the group consisting of boron hydride, sodium hydride, aluminum hydride, sodium borohydride (NaBH4), sodium cyanoborohydride (NaCNBH 3 ), sodium triacetoxyborohydride (NaBH(OAc) 3 ), borane-pyridine complexe (BH 3 -Py), resin-supported hydride, and polymer-supported hydride.
5. The process according to claim 4 , wherein said hydride donating agent is NaBH(OAc) 3 .
6. The process according to claim 1 , wherein said organic carboxylic acid is selected from the group consisting of aliphatic acid, aromatic acid, dicarboxylic acid, and resin-supported organic carboxylic acid.
7. The process according to claim 6 , wherein said organic carboxylic acid is aliphatic acid.
8. The process according to claim 7 , wherein said aliphatic acid is selected from the group consisting of acetic acid, formic acid, and trifluoroacetic acid.
9. The process according to claim 8 , wherein said aliphatic acid is acetic acid.
10. The process according to claim 6 , wherein said carboxylic acid is aromatic acid.
11. The process according to claim 10 , wherein said aromatic acid is benzoic acid or salicylic acid.
12. The process according to claim 6 , wherein said carboxylic acid is dicarboxylic acid.
13. The process according to claim 12 , wherein said dicarboxylic acid is oxalic acid or phthalic acid.