Sulfur → 1-(4-fluorophenylmethyl)-N-[1-{2-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]ethyl}-4-piperidinyl]-1H-benzimidazol-2-amine

HRID 1856583Notes

Reaction equation

HRID 1856583 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[NH:16][C:17]([NH:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][CH:25]([NH:28][C:29]3[N:33]([CH2:34][C:35]4[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=4)[C:32]4[CH:42]=[CH:43][CH:44]=[CH:45][C:31]=4[N:30]=3)[CH2:24][CH2:23]2)=S)=[CH:4][CH:3]=1.[S]>[Hg]=O.O1CCCC1>[F:41][C:38]1[CH:39]=[CH:40][C:35]([CH2:34][N:33]2[C:32]3[CH:42]=[CH:43][CH:44]=[CH:45][C:31]=3[N:30]=[C:29]2[NH:28][CH:25]2[CH2:26][CH2:27][N:22]([CH2:21][CH2:20][NH:19][C:17]3[N:9]([CH2:8][C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=4[N:16]=3)[CH2:23][CH2:24]2)=[CH:36][CH:37]=1

Participants

5

Reactant 2

HCID 5362487SulfurHCID 53996556N-{2-[(4-fluorophenylmethyl)amino]phenyl}-N'-[2-{4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidinyl}ethyl]thiourea

Product 1

HCID 128917541-(4-fluorophenylmethyl)-N-[1-{2-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]ethyl}-4-piperidinyl]-1H-benzimidazol-2-amineYield 20%

Reagents, catalysts & solvents 2

HCID 30856Mercuric oxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 6 parts of N-{2-[(4-fluorophenylmethyl)amino]phenyl}-N'-[2-{4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidinyl}ethyl]thiourea, 3.2 parts of mercury (II) oxide, 0.1 parts of sulfur. and 90 parts of tetrahydrofuran is stirred and refluxed for 3 hours. The reaction mixture is filtered over Hyflo and the filtrate is evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from a mixture of 2-propanone and 2,2'-oxybispropane, yielding 1.2 parts (20%) of 1-(4-fluorophenylmethyl)-N-[1-{2-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]ethyl}-4-piperidinyl]-1H-benzimidazol-2-amine; mp. 196.9° C.

Workup

  1. temperaturerefluxed for 3 hours
  2. filtrationThe reaction mixture is filtered over Hyflo
  3. customthe filtrate is evaporated
  4. customThe residue is purified by column-chromatography over silica gel using
  5. additiona mixture of trichloromethane and methanol (98:2 by volume) as eluent
  6. customThe pure fractions are collected
  7. customthe eluent is evaporated
  8. customThe residue is crystallized from a mixture of 2-propanone and 2,2'-oxybispropane

Sources & evidence

ORD record
ord-59645d9a4df64065bf5a8558fc675b5b
Source dataset
uspto-grants-1980_08
Patent number
US04219559

Reaction notes

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