4,5-Dihydro-2-(methylthio)-1h-imidazole-1-carboxylic acid methyl ester → HCID 178501934, compound
Reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:12]#[N:13])[C:5]2[N:9]=[CH:8][NH:7][C:6]=2[C:10]=1[CH3:11].CS[C:16]1[N:17]([C:21]([O:23][CH3:24])=[O:22])[CH2:18][CH2:19][N:20]=1>>[CH3:24][O:23][C:21]([N:17]1[CH2:18][CH2:19][NH:20][C:16]1=[N:1][C:2]1[CH:3]=[C:4]([C:12]#[N:13])[C:5]2[NH:9][CH:8]=[N:7][C:6]=2[C:10]=1[CH3:11])=[O:22]Participants
Procedure
There are many suitable methods for coupling intermediate (10) with side chain 4,5-Dihydro-2-(methylthio)-1H-imidazole-1-carboxylic Acid, Methyl Ester (29). Referring to General Scheme (4), intermediate (10) is coupled to side chain (29) to yield intermediate 2-(7-Cyano-4-methyl-1H-benzimidazol-5-yl-imino)-imidazolidine-1-carboxylic Acid Methyl Ester (30), and thereafter deprotected to yield product 6-[(4,5-Dihydro-1H-imidazol-2-yl)amino-]-7-methyl-1H-benzimidazole-4-carbonitrile (31a) as the preferred anhydrous, monoacetate salt (which can be further purified by recrystallization to yield final product (31b)). See Example 5. The assay described in Example 3 may be used to analyze products (31a) and (31b) for the level of 2,3,7-triamino-4,6-dimethyl-1,9-phenazinedicarbonitrile that is present. In one embodiment, the preferred anhydrous monoacetate salt of 6-[(4,5-Dihydro-1H-imidazol-2-yl)amino-]-7-methyl-1H-benzimidazole-4-carbonitrile (31a) and (31b) that is produced is substantially free of 2,3,7-triamino-4,6-dimethyl-1,9-phenazinedicarbonitrile. In one embodiment, the preferred anhydrous monoacetate salt of 6-[(4,5-Dihydro-1H-imidazol-2-yl)amino-]-7-methyl-1H-benzimidazole-4-carbonitrile (31a) and (31b) that is produced contains less than 70 ppb (parts per billion), preferably less than 15 ppb, more preferably less than 5 ppb, of 2,3,7-triamino-4,6-dimethyl-1,9-phenazinedicarbonitrile. Other solvent systems that may be used to recrystallize product (31a) to yield final product (31b) include: ethanol/water, acetone/water, acetonitrile/water, tetrahydrofuran/water, methanol, N,N-dimethylacetamide, and acetonitrile. Although in General Scheme 4 intermediate (30) is carried forward without isolation, it may be isolated as shown in Example 16. Another method to attach the side chain includes Example 17. Still another suitable method is described in U.S. Pat. No. 6,066,740.
Sources & evidence
- ORD record
- ord-c5094c1d8eec4d6db6078d03b6e0841d
- Source dataset
- uspto-grants-2007_12
- Patent number
- US07304084B2
Reaction notes
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