Chloroacetyl chloride → 1-(4-Benzylpiperidinecarbonyl)methyl-5-cyanobenzimidazole

HRID 1419609Notes

Reaction equation

HRID 1419609 reaction equation
C(C1CCNCC1)C1C=CC=CC=1.ClCC(Cl)=O.[C:19]([C:21]1[CH:29]=[CH:28][C:24]2[N:25]=[CH:26][NH:27][C:23]=2[CH:22]=1)#[N:20].[CH2:30]([CH:37]1[CH2:42][CH2:41][N:40]([C:43]([CH:45]([Cl:47])[Cl:46])=[O:44])[CH2:39][CH2:38]1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[H-].[Na+]>C1COCC1.C([O-])([O-])=O.[K+].[K+].CN(C=O)C>[CH2:30]([CH:37]1[CH2:38][CH2:39][N:40]([C:43]([CH:45]([Cl:47])[Cl:46])=[O:44])[CH2:41][CH2:42]1)[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1.[CH2:30]([CH:37]1[CH2:38][CH2:39][N:40]([C:43]([CH2:45][N:27]2[C:23]3[CH:22]=[C:21]([C:19]#[N:20])[CH:29]=[CH:28][C:24]=3[N:25]=[CH:26]2)=[O:44])[CH2:41][CH2:42]1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[CH2:30]([CH:37]1[CH2:38][CH2:39][N:40]([C:43]([CH2:45][N:25]2[C:24]3[CH:28]=[CH:29][C:21]([C:19]#[N:20])=[CH:22][C:23]=3[N:27]=[CH:26]2)=[O:44])[CH2:41][CH2:42]1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

11

Reactant 5

HCID 6577Chloroacetyl chlorideHCID 24758Sodium hydrideHCID 317384-BenzylpiperidineHCID 2239061H-Benzimidazole-6-carbonitrileHCID 4251733(4-Benzylpiperidinecarbonyl)methylene chloride

Product 3

HCID 4251733(4-Benzylpiperidinecarbonyl)methylene chlorideHCID 154629441-(4-Benzylpiperidinecarbonyl)methyl-6-cyanobenzimidazoleHCID 188005711-(4-Benzylpiperidinecarbonyl)methyl-5-cyanobenzimidazoleYield 167.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 11430Potassium CarbonateSolvent

Procedure

(4-Benzylpiperidinecarbonyl)methylene chloride was prepared by acylation of 4-benzylpiperidine (100 mmol) with a-chloroacetyl chloride (100 mmol) in THF (250 mL) and K2CO3 (100 mL. Alkylation of 5-cyanobenzimidazole (2 mmol) with (4-benzylpiperidinecarbonyl)methylene chloride (2 mmol) in DMF (5 mL) in the presence of NaH (3 mmol) at from 0° C. to room temperature over 16 hours, followed by purification on TLC plates gave 1-(4-benzylpiperidinecarbonyl)methyl-6-cyanobenzimidazole and 1-(4-benzylpiperidinecarbonyl)methyl-5-cyanobenzimidazole (0.4 g, 56% of yield). This mixture (1.11 mmol) was then carried through the Pinner reaction, followed by purification on TLC plates with 10% MeOH in CH2Cl2, and further purification by HPLC to give the title compounds: MP: 54°-56° C.; MS: 376.4 (M+H)+ ; HRMS: 376.2118 (obs.), 376.2137 (calcd.); Anal.: (C22H25N5O1 +1.8TFA+0.1 HCl).

Workup

  1. customfollowed by purification on TLC plates

Sources & evidence

ORD record
ord-66752642933f44f2b9abefede4920977
Source dataset
uspto-grants-1999_03
Patent number
US05886191

Reaction notes

Loading…