Coupling process for preparing quinolone intermediates
View Patent ↗Process for making 7-cycloamino-1-cyclopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acids. Borate ester compounds suitable for use in such process.
1. A process for perparing a substituted quinolone according to Formula I:
wherein:
R 1 is C 1 -C 4 alkyl;
R 2 is C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl;
R 4 and R 5 are each independently selected from a group consisting of amino, C 1 -C 4 alkylamino, protected amino, and C 1 C 4 alkyl; and
n is 1 or 2;
said process comprising: the step of reacting a compound of Formula II with compound of Formula III in the presence of a suitable base at about 20° C. to about 80° C., followed by hydrolysis:
wherein:
R 3 is acetoxy; and
R 1 ,R 2 ,R 4 ,R 5 , and n are as defined for Formula I above.
2. A process for preparing a substituted quinolone according to Formula I:
wherein:
R 1 is C 1 -C 4 alkyl;
R 2 is C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl;
R 4 is selected from a group consisting of amino, C 1 -C 4 alkylamino, protected amino, and C 1 -C 4 alkyl;
R 5 is amino-tert-butoxycarbonyl; and
n is 1 or 2;
said process comprising: the step of reacting a compound of Formula II with compound of Formula III in the presence of a suitable base at about 20° C. to about 80° C., followed by hydrolysis:
wherein:
R 3 is unsubstituted or substituted C 1 -C 4 acyloxy; and
R 1 ,R 2 ,R 4 ,R 5 , and n are as defined for Formula I above.
3. A process according to claim 2 , wherein the resulting compound of Formula I is subsequently subjected to a process of deprotecting the amino group of R 5 .
4. A process for preparing a substituted quinolone according to Formula I:
wherein:
R 1 is C 1 -C 4 alkyl;
R 2 is C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl;
R 4 is methyl;
R 5 is amino-tert-butoxycarbonyl; and
n is 2;
said process comprising: the step of reacting a compound of Formula II with compound of Formula III in the presence of a suitable base at about 20° C. to about 80° C., followed by hydrolysis:
wherein:
R 3 is unsubstituted or substituted C 1 -C 4 acyloxy;
R 1 and R 2 are as defined for Formula I above; and
the compound of Formula III is:
5. A process for preparing a substituted quinolone according to Formula I:
wherein:
R 1 is C 1 -C 4 alkyl;
R 2 is C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl;
R 4 and R 5 are each independently selected from a group consisting of amino, C 1 -C 4 alkylamino, protected amino, and C 1 C 4 alkyl; and
n is 1 or 2;
said process comprising: the step of reacting a compound of Formula II with compound of Formula III in the presence of a suitable base at about 20° C. to about 80° C., followed by hydrolysis:
wherein:
the base is selected from the group consisting of triethylamine,
diisopropylethylamine, triisopropyl amine, and 1,8-diazabicyclo[5.4.0]undec-7-ene;
R 3 is unsubstituted or substituted C 1 -C 4 acyloxy; and
R 1 ,R 2 ,R 4 ,R 5 , and n are as defined for Formula I above.
6. A process according to claim 5 , wherein the base is triethylamine.