2-Chlorobenzothiazole → N-[1-[2-(2-benzothiazolyloxy)ethyl]-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-amine

HRID 979934Notes

Reaction equation

HRID 979934 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[NH:18][CH:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][OH:27])[CH2:21][CH2:20]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:31]1[S:32][C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[N:35]=1>CN(C)C=O>[S:32]1[C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[N:35]=[C:31]1[O:27][CH2:26][CH2:25][N:22]1[CH2:23][CH2:24][CH:19]([NH:18][C:10]2[N:9]([CH2:8][C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=2)[CH2:20][CH2:21]1

Participants

5

Reactant 3

HCID 119872-ChlorobenzothiazoleHCID 24758Sodium hydrideHCID 128916994-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidineethanol

Product 1

HCID 13769694N-[1-[2-(2-benzothiazolyloxy)ethyl]-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-amineYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of 5.5 parts of 4-[1-[(4-fluorophenyl)-methyl]-1H-benzimidazol-2-ylamino]-1-piperidineethanol and 135 parts of N,N-dimethylformamide were added 0.75 parts of a sodium hydride dispersion 50%. After stirring for 30 minutes at room temperature, 2.54 parts of 2-chlorobenzothiazole were added and the whole was further stirred for 3 hours. The reaction mixture was poured onto water and the product was extracted with 4-methyl-2-pentanone. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (96:4 by volume) saturated with ammonia, as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile, yielding 4.6 parts (61%) of N-[1-[2-(2-benzothiazolyloxy)ethyl]-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-amine; mp. 147.0° C. (compound 67).

Workup

  1. stirringthe whole was further stirred for 3 hours
  2. additionThe reaction mixture was poured onto water
  3. extractionthe product was extracted with 4-methyl-2-pentanone
  4. customThe extract was dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol (96:4 by volume) saturated with ammonia
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customThe residue was crystallized from acetonitrile

Sources & evidence

ORD record
ord-7d38d7cfecb74a3082d4ee983ca3602d
Source dataset
uspto-grants-1987_01
Patent number
US04634704

Reaction notes

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