Methods of making 6-[(4,5-Dihydro-1H-imidazol-2-yl)amino-]-7-methyl-1H-benzimidazole-4-carbonitrile and its preferred salt form

A method of making a compound of formula (II):

• 63
• wherein:
• (a) Q1, and Q3 are each independently selected from the group consisting of hydrogen, hydrogen functional group equivalent and nil;
• (b) Q2 is selected from the group consisting of hydrogen, and hydrogen functional group equivalent;
• (c) R4 is selected from the group consisting of amide, carboxylic acid, cyano, carboxylic acid functional group equivalent and cyano functional group equivalent;
• (d) Q5 is selected from hydrogen or hydrogen functional group equivalent;
• (e) R6 is selected from the group consisting of amino, nitro, formylamino, and amino functional group equivalent;
• and
• (f) R7 is either methyl or methyl functional group equivalent;
• (g) or tautomer thereof;
• comprising:
• a) providing a compound of formula (I):
• 64
• wherein:
• (a) X and Y are each independently selected from the group consisting of nitro, amino, formylamino and nitrogen/one carbon equivalent conjugate, and amino functional group equivalent;
• (b) R4 is selected from the group consisting of carboxylic acid, cyano, carboxylic acid functional group equivalent, and cyano functional group equivalent;
• (c) Q5 is selected from hydrogen or hydrogen functional group equivalent;
• (d) R6 is selected from the group consisting of hydrogen, amino, nitro, and amino functional group equivalent;
• (e) R7 is selected from methyl or methyl functional group equivalent;
• (f) provided X and Y are not both amino;
• and
• (g) provided X and Y are not both nitrogen/one carbon equivalent conjugate.
• b) cyclizing the formula (I) compound in a single pot by using a non ferrous metal hydrogenation catalyst, in the presence of hydrogen or a hydrogen donor, and optionally a cyclization agent, yielding the compound of formula (II).

A composition comprising 7-Cyano-4-methyl-1H-benzimidazol-5-amine substantially free of a compound of formula III comprising:

• 66
• wherein:
• (a) Q11, Q12 and Q13 are each independently selected from the group consisting of nitro, amino, formylamino and amino functional group equivalent;
• (b) R11 and R12 are each independently selected from methyl or methyl functional group equivalent;
• and
• (c) R13 and R14 are each independently selected from the group consisting of amide, carboxylic acid, cyano, and cyano functional group equivalent.