Acetyl chloride → HCID 18916382, compound

Participants

Reaction Steps

Additional moieties may also be added to the benzoxazole ring at this point. For example, bromine moieties are added to 3-(2-methyl-4-chloro-6-fluorobenzoxazol-7-yl)-1-methyl-6-trifluoromethyl-2,4-(1H,3H)-pyrimidinedione by reacting it with N-bromosuccinimide under basic conditions, yielding the corresponding 3-(2-dibromomethyl-4-chloro-6-fluorobenzoxazol-7-yl)-1-methyl-6-trifluoromethyl-2,4-(1H,3H)-pyrimidinedione (VB). An alkyl group can also be added to 3-(2-thio-4-chloro-6-fluorobenzoxazol-7-yl)-1-methyl-6-trifluoromethyl-2,4-(1H,3H)-pyrimidinedione by reacting it with an alkyl halide in the manner described previously, yielding the appropriate 3-(2-alkylthio-4-chloro-6-fluorobenzoxazol-7-yl)-1-methyl-6-trifluoromethyl-2,4-(1H,3H)-pyrimidinedione (VC). In addition, (V), where R in the 2-position is amino may be further reacted to add additional moieties to the amine. For example, an acetyl moiety is added to 3-(2-amino-4-chloro-6-fluorobenzoxazol-7-yl)-1-methyl-6-trifluoromethyl-2,4-(1H,3H)-pyrimidinedione by reacting it with acetyl chloride in the presence of pyridine affording 3-(2-acetylamino-4-chloro-6-fluorobenzoxazol-7-yl)-1-methyl-6-trifluoromethyl-2,4-(1H,3H)-pyrimidinedione (VD). The so-prepared pyrimidinedione (VD) is in turn reacted with sodium hydride and methanesulfonyl chloride to form the appropriate 3-[2-(N-acetyl-N-methylsulfonylamino)-disubstituted-benzoxazol-7-yl]-1-methyl-6-trifluoromethyl-2,4-(1H,3H)-pyrimidinedione (VE), which is hydrogenated under acidic conditions affording 3-(2-methylsulfonylamino-disubstituted-benzoxazol-7-yl)-1-methyl-6-trifluoromethyl-2,4-(1H,3H)-pyrimidinedione (VF). The pyrimidinedione (VF) is in turn alkylated in the manner described previously, affording 3-[2-(N-alkyl-N-methylsulfonyl-amino)-disubstituted-benzoxazol-7-yl]-1-methyl-6-trifluoromethyl-2,4-(1H,3H)-pyrimidinedione (VG). Examples 14, 17, 20, 21, 22, and 23 provide the detailed procedures for this route.

Provenance & Evidence