PROCESS FOR PREPARING 4-AMINOPYRIDINES USING PYRIDINE BETAINE INTERMEDIATES AND PYRIDINE BETAINES

摘要

The invention provides a process for preparing a 4-(secondary or tertiary)aminopyridine, comprising: reacting a 4-substituted pyridine base having a leaving group as the 4-substituent, with an activating agent of the formula: <IMG> wherein R3 and R4, which may be the same as or may differ from one another, are each -H or a C1-C4 alkyl group, and Z is -OR7 or NR5R6, wherein R5 and R6, which may be the same as or may differ from one another, and may taken together form a ring, are each -H or Cl-C8 alkyl; and R7 is -H or C1-C8 alkyl; so as to form a corresponding 1,4-substituted pyridine; reacting said 1,4-substituted pyridine with a primary or secondary amine to substitute an amino group for the leaving group at the 4-position, and thereby form a corresponding 1-substituted-4-(secondary or tertiary)aminopyridine, wherein said amine is included in a molar ratio of at least about 2:1 relative to the 1,4-substituted pyridine and said reacting is conducted in a substitution reaction medium essentially free from strong base; and treating the 1-substituted-4-aminopyridine compound to remove the 1-substituent and thereby form a product medium including the 4-(secondary or tertiary)amino- pyridine as well as a process for preparing a 4-substituted pyridine compound, which comprises: first reacting a 4-substituted pyridine base having a leaving group as the 4-substituent, with an a-unsaturated acid of the formula <IMG> wherein R3 and R4, which may be the same as or may differ from one another, are each -H or a C1-C4 alkyl group; so as to form a corresponding first 1,4-substituted pyridine betaine; second reacting the 1,4-substituted betaine with a nucleophile to displace the leaving group and form a second 1,4-substituted-pyridine betaine; and treating the second 1,4-substituted betaine to remove the 1-substituent and form the 4-substitued pyridine compound. The products produced by these processes are useful as catalysts in acylation reactions. The invention also provides pyridine betaine intermediates useful in these processes as well as more pyridine betaine intermediates.