Process for the synthesis of an indoleamine 2,3-dioxygenase inhibitor
The present application is directed to processes and intermediates for making 4-({2-[(aminosulfonyl)amino]ethyl}amino)-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide, which is an inhibitor of indoleamine 2,3-dioxygenase, useful in the treatment of cancer and other disorders.
1. A compound of Formula F16:
or a salt thereof, wherein:
each R 1 is independently an amino protecting group; and
R 3 is C 1-6 alkyl or benzyl.
2. The compound of claim 1 , or a salt thereof, wherein R 1 is C 2-4 alkenyl-C 1-3 alkyl or phenyl-C 1-3 alkyl, wherein said phenyl-C 1-3 alkyl is optionally substituted by 1, 2, or 3 independently selected C 1-4 alkoxy groups.
3. The compound of claim 1 , or a salt thereof, wherein R 1 is allyl.
4. The compound of claim 1 , or a salt thereof, wherein R 1 is 4-methoxybenzyl.
5. The compound of claim 1 , or a salt thereof, wherein R 3 is C 1-6 alkyl.
6. The compound of claim 1 , or a salt thereof, wherein R 3 is C 1-4 alkyl.
7. The compound of claim 1 , or a salt thereof, wherein R 3 is tert-butyl.
8. The compound of claim 1 , or a salt thereof, wherein R 3 is butyl.
9. The compound of claim 1 , wherein the compound of Formula F16 is tert-butyl allyl(N-allyl-N-(2-(4-(4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1,2,5-oxadiazol-3-ylamino)ethyl)sulfamoyl)carbamate, or a salt thereof.
10. The compound of claim 1 , wherein the compound of Formula F16 is tert-butyl allyl(N-allyl-N-(2-(4-(4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1,2,5-oxadiazol-3-ylamino)ethyl) sulfamoyl)carbamate.
11. The compound of claim 1 , wherein the compound of Formula F16 is tert-butyl (4-methoxybenzyl)-(N-(4-methoxybenzyl)-N-(2-(4-(4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1,2,5-oxadiazol-3-ylamino)ethyl)sulfamoyl)carbamate, or a salt thereof.
12. The compound of claim 1 , wherein the compound of Formula F16 is tert-butyl (4-methoxybenzyl)-(N-(4-methoxybenzyl)-N-(2-(4-(4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1,2,5-oxadiazol-3-ylamino)ethyl)sulfamoyl)carbamate.