Dimethylformamide → 1-[(4-fluorophenyl)methyl]-N-[1-[2-(thiazolo[5,4-b]pyridin-2-ylthio)ethyl]-4-piperidinyl]-1H-benzimidazol-2-amine

HRID 2309523Notes

Reaction equation

HRID 2309523 reaction equation
[N:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[S:3][C:2]=1[SH:10].[H-].[Na+].CN(C)C=O.Cl[CH2:19][CH2:20][N:21]1[CH2:26][CH2:25][CH:24]([NH:27][C:28]2[N:32]([CH2:33][C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=3)[C:31]3[CH:41]=[CH:42][CH:43]=[CH:44][C:30]=3[N:29]=2)[CH2:23][CH2:22]1>O>[F:40][C:37]1[CH:38]=[CH:39][C:34]([CH2:33][N:32]2[C:31]3[CH:41]=[CH:42][CH:43]=[CH:44][C:30]=3[N:29]=[C:28]2[NH:27][CH:24]2[CH2:23][CH2:22][N:21]([CH2:20][CH2:19][S:10][C:2]3[S:3][C:4]4[C:9]([N:1]=3)=[CH:8][CH:7]=[CH:6][N:5]=4)[CH2:26][CH2:25]2)=[CH:35][CH:36]=1

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 12891727N-[1-(2-chloroethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amineHCID 178527801HCID 178527801, compound

Product 1

HCID 139831061-[(4-fluorophenyl)methyl]-N-[1-[2-(thiazolo[5,4-b]pyridin-2-ylthio)ethyl]-4-piperidinyl]-1H-benzimidazol-2-amineYield 6.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 2.5 parts of thiazolo[5,4-b]pyridine-2-thiol, 1 part of a sodium hydride dispersion 50% and 45 parts of N,N-dimethylformamide was stirred for 1 hour. Then there was added a solution of 6.9 parts of N-[1-(2-chloroethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine in 45 parts of N,N-dimethylformamide. The whole was stirred overnight. Water was added dropwise. 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, saturated with ammonia, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 0.5 parts (6.4%) of 1-[(4-fluorophenyl)methyl]-N-[1-[2-(thiazolo[5,4-b]pyridin-2-ylthio)ethyl]-4-piperidinyl]-1H-benzimidazol-2-amine; mp. 159.9° C. (compound 105).

Workup

  1. stirringThe whole was stirred overnight
  2. extractionThe product was extracted with 4-methyl-2-pentanone
  3. customThe extract was dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography over silica gel using
  7. additiona mixture of trichloromethane and methanol
  8. customThe pure fractions were collected
  9. customthe eluent was evaporated
  10. customThe residue was crystallized from acetonitrile
  11. filtrationThe product was filtered off
  12. customdried

Sources & evidence

ORD record
ord-c04df2999c234b36a464b7d8c72bde10
Source dataset
uspto-grants-1987_09
Patent number
US04695569

Reaction notes

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