Tributylamine → 3-amino-N-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-2-pyrazinecarboxamide

HRID 637430Notes

Reaction equation

HRID 637430 reaction equation
N[C:2]1([C:8]([OH:10])=O)[N:7]=[CH:6][CH:5]=[N:4][CH2:3]1.C([N:15](CCCC)CCCC)CCC.[I-].ClC1C=CC=C[N+]=1C.[NH2:33][CH2:34][CH2:35][N:36]1[CH2:41][CH2:40][CH:39]([NH:42][C:43]2[N:47]([CH2:48][C:49]3[CH:54]=[CH:53][C:52]([F:55])=[CH:51][CH:50]=3)[C:46]3[CH:56]=[CH:57][CH:58]=[CH:59][C:45]=3[N:44]=2)[CH2:38][CH2:37]1>ClCCl>[NH2:15][C:3]1[C:2]([C:8]([NH:33][CH2:34][CH2:35][N:36]2[CH2:41][CH2:40][CH:39]([NH:42][C:43]3[N:47]([CH2:48][C:49]4[CH:54]=[CH:53][C:52]([F:55])=[CH:51][CH:50]=4)[C:46]4[CH:56]=[CH:57][CH:58]=[CH:59][C:45]=4[N:44]=3)[CH2:38][CH2:37]2)=[O:10])=[N:7][CH:6]=[CH:5][N:4]=1

Participants

6

Reactant 4

HCID 7622TributylamineHCID 1670692-Chloro-1-methylpyridinium iodideHCID 12891741N-[1-(2-aminoethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amineHCID 70488794HCID 70488794, compound

Product 1

HCID 135881203-amino-N-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-2-pyrazinecarboxamideYield 38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of 2.1 parts of 3-amino-3-pyrazinecarboxylic acid, 2.8 parts of N,N-dibutylbutanamine and 195 parts of dichloromethane were added 3.83 parts of 2-chloro-1-methylpyridinium iodide. After stirring for 15 minutes at room temperature, 5.5 parts of N-[1-(2-aminoethyl)-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-amine were added and stirring was continued for one hour. The reaction mixture was washed with water, dried, filtered and evaporated. The residue was stirred in 2,2'-oxybispropane. The latter was decanted and the residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (96:4 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 1,1'-oxybisethane, yielding 2.8 parts (38%) of 3-amino-N-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-2-pyrazinecarboxamide; mp. 156.9° C. (compound 113).

Workup

  1. stirringstirring
  2. waitwas continued for one hour
  3. washThe reaction mixture was washed with water
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. stirringThe residue was stirred in 2,2'-oxybispropane
  8. customThe latter was decanted
  9. customthe residue was purified by column-chromatography over silica gel using
  10. additiona mixture of trichloromethane and methanol (96:4 by volume) as eluent
  11. customThe pure fractions were collected
  12. customthe eluent was evaporated
  13. customThe residue was crystallized from 1,1'-oxybisethane

Sources & evidence

ORD record
ord-69e2e516e4a84091b44941e71401e5eb
Source dataset
uspto-grants-1985_12
Patent number
US04556660

Reaction notes

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