Potassium Iodide → 1-[(4-fluorophenyl)methyl]-N-[1'-[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]-[1,4'-bipiperidin]-4-yl]-1H-benzimidazol-2-amine monohydrate

HRID 979933Notes

Reaction equation

HRID 979933 reaction equation
Cl[C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[C:5]2[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=2[N:3]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][N:27]2[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=3[N:29]=[C:28]2[NH:36][CH:37]2[CH2:42][CH2:41][N:40]([CH:43]3[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]3)[CH2:39][CH2:38]2)=[CH:22][CH:21]=1.[I-].[K+].C(=O)([O-])[O-:52].[K+].[K+]>O.ClC(Cl)Cl>[OH2:52].[F:19][C:20]1[CH:21]=[CH:22][C:23]([CH2:26][N:27]2[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=3[N:29]=[C:28]2[NH:36][CH:37]2[CH2:42][CH2:41][N:40]([CH:43]3[CH2:48][CH2:47][N:46]([C:2]4[N:6]([CH2:7][C:8]5[CH:9]=[CH:10][C:11]([F:14])=[CH:12][CH:13]=5)[C:5]5[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=5[N:3]=4)[CH2:45][CH2:44]3)[CH2:39][CH2:38]2)=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 30202411-(4-Fluorobenzyl)-2-chlorobenzimidazoleHCID 15614720N-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-yl][1,4'-bipiperidine]-4-amine

Product 1

HCID 202228991-[(4-fluorophenyl)methyl]-N-[1'-[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]-[1,4'-bipiperidin]-4-yl]-1H-benzimidazol-2-amine monohydrate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 4 parts of 2-chloro-1-[(4-fluorophenyl)methyl]-1H-benzimidazole, 6.1 parts of N-[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]-[1,4'-bipiperidine]-4-amine and 1 part of potassium iodide was stirred and heated for 3 hours at 130° C. The reaction mixture was cooled and taken up in water and trichloromethane. The whole was alkalized with potassium carbonate. The organic phase was separated, dried, filtered and evaporated. The residue was purified by HPLC using a mixture of trichloromethane and methanol (98:2 by volume), saturated with ammonia, as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile, yielding 1.6 parts of 1-[(4-fluorophenyl)methyl]-N-[1'-[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]-[1,4'-bipiperidin]-4-yl]-1H-benzimidazol-2-amine monohydrate; mp. 130.2° C. (compound 65).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customThe organic phase was separated
  3. customdried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by HPLC
  7. additiona mixture of trichloromethane and methanol (98:2 by volume)
  8. customThe pure fractions were collected
  9. customthe eluent was evaporated
  10. customThe residue was crystallized from acetonitrile

Sources & evidence

ORD record
ord-c4cd608fbc59417dbc9f07e033b48523
Source dataset
uspto-grants-1987_01
Patent number
US04634704

Reaction notes

Loading…