Reaction equation
Br[C:2]1[CH:18]=[CH:17][C:5]2[NH:6][C:7]([CH2:9][CH2:10][N:11]3[CH2:15][CH2:14][CH2:13][CH:12]3[CH3:16])=[N:8][C:4]=2[CH:3]=1.[C:19]([C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1)#[N:20]>>[CH3:16][CH:12]1[CH2:13][CH2:14][CH2:15][N:11]1[CH2:10][CH2:9][C:7]1[NH:6][C:5]2[CH:17]=[CH:18][C:2]([C:24]3[CH:25]=[CH:26][C:21]([C:19]#[N:20])=[CH:22][CH:23]=3)=[CH:3][C:4]=2[N:8]=1Participants
Procedure
Compounds of formula (55) and (55a) can be prepared from 2(R)-methylpyrrolidine HCl (50) and ethyl acrylate (51) as shown in Scheme 6. 2(R)-Methylpyrrolidine HCl can be treated with potassium carbonate to provide 2(R)-methylpyrrolidine (41), which is reacted with ethyl acrylate (51) to provide 3-(2-methyl-pyrrolidin-1-yl)-propionic acid ethyl ester (52). Compound (52) is reacted with 4-bromo-benzene-1,2-diamine (53), which is produced by controlled hydrogenation of 2-amino-5-bromo-nitrobenzene, Chemical Abstracts number 875-51-4, to provide 5-bromo-2-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-1H-benzoimidazole (54). Compound (54) can be reacted with a 4-cyanophenylboronic acid to provide 4-{2-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-1H-benzoimidazol-5-yl}-benzonitrile (55). As previously described for Scheme 5, the amine compound (41) can be any amine of the formula HNRaRb, wherein Ra and Rb are as defined for R4 and R5. Also, the 4-cyanophenylboronic acid can be replaced with any boronic acid of the formula RcB(OH)2, wherein Rc is aryl or heteroaryl to provide compounds of general structure (55a). Additionally, compounds (55) and (55a) may be alkylated on the benzimidazole nitrogen by treatment with a base, such as cesium carbonate, and an alkylating agent, such as methyl iodide.
Sources & evidence
- ORD record
- ord-d7024dd9e5254cfbaa00ffa5e9ae3740
- Source dataset
- uspto-grants-2006_08
- Patent number
- US07094790B2
Linked notes
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