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

HRID 2309525Notes

Reaction equation

HRID 2309525 reaction equation
Cl.Cl.[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[N:13]=[C:12]2[NH:20][CH:21]2[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][OH:29])[CH2:23][CH2:22]2)=[CH:6][CH:5]=1.[H-].[Na+].CN(C)C=O.CS([C:41]1[S:42][C:43]2[C:48]([N:49]=1)=[CH:47][CH:46]=[CH:45][N:44]=2)(=O)=O>O>[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[N:13]=[C:12]2[NH:20][CH:21]2[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][O:29][C:41]3[S:42][C:43]4[C:48]([N:49]=3)=[CH:47][CH:46]=[CH:45][N:44]=4)[CH2:23][CH2:22]2)=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 36045032-(Methylsulfonyl)thiazolo[5,4-b]pyridineHCID 679186284-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidineethanol dihydrochloride

Product 1

HCID 139831081-[(4-fluorophenyl)methyl]N-[1-[2-[(thiazolo[5,4-b]pyridin-2-yl)oxy]ethyl]-4-piperidinyl]-1H-benzimidazol-2-amineYield 15%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred mixture of 5.3 parts of 4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidineethanol dihydrochloride, 2.8 parts of a sodium hydride dispersion 50% and 90 parts of N,N-dimethylformamide were added 2.55 parts of 2-(methylsulfonyl)thiazolo[5,4-b]pyridine. The whole was stirred for 2 hours. The reaction mixture was poured into water. 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, hexane and methanol (45:45:10 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 0.9 parts (15%) of 1-[(4-fluorophenyl)methyl]-N-[1-[2-[(thiazolo[5,4-b]pyridin-2-yl)oxy]ethyl]-4-piperidinyl]-1H-benzimidazol-2-amine; mp. 151.0° C. (compound 107).

Workup

  1. extractionThe product was extracted with 4-methyl-2-pentanone
  2. customThe extract was dried
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by column chromatography over silica gel using
  6. additiona mixture of trichloromethane, hexane and methanol (45:45:10 by volume) as eluent
  7. customThe pure fractions were collected
  8. customthe eluent was evaporated
  9. customThe residue was crystallized from acetonitrile
  10. filtrationThe product was filtered off
  11. customdried

Sources & evidence

ORD record
ord-81e92dcd1cb342eaadb15a30c6655788
Source dataset
uspto-grants-1987_09
Patent number
US04695569

Reaction notes

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