Ammonia → N6-[2-[4-[[1-[(4-fluorophenyl)methyl]1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-3-nitro-2,6-pyridinediamine

HRID 477666Notes

Reaction equation

HRID 477666 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH2:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1.[NH2:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:22]2[N:26]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[C:25]3[CH:35]=[CH:36][CH:37]=[CH:38][C:24]=3[N:23]=2)[CH2:17][CH2:16]1.CN1CCCC1=O.N>CO>[F:34][C:31]1[CH:32]=[CH:33][C:28]([CH2:27][N:26]2[C:25]3[CH:35]=[CH:36][CH:37]=[CH:38][C:24]=3[N:23]=[C:22]2[NH:21][CH:18]2[CH2:19][CH2:20][N:15]([CH2:14][CH2:13][NH:12][C:2]3[N:7]=[C:6]([NH2:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=3)[CH2:16][CH2:17]2)=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 13387N-methyl-2-pyrrolidoneHCID 27240356-Chloro-3-nitropyridin-2-ylamineHCID 12891741N-[1-(2-aminoethyl)-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine

Product 1

HCID 13588113N6-[2-[4-[[1-[(4-fluorophenyl)methyl]1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-3-nitro-2,6-pyridinediamineYield 50%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 3.4 parts of 6-chloro-3-nitro-2-pyridinamine, 7.4 parts of N-[1-(2-aminoethyl)-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-amine and 10 parts of 1-methyl-2-pyrrolidinone was stirred and heated for 2 hours at 150° C. The reaction mixture was cooled and taken up in methanol saturated with ammonia. The whole was evaporated and water was added to the residue. The product was extracted three times with 4-methyl-2-pentanone. The combined extracts were dried, filtered and evaporated in vacuo. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 4-methyl-2-pentanone, yielding 5 parts (50%) of N6 -[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]-amino]-1-piperidinyl]ethyl]-3-nitro-2,6-pyridinediamine; mp. 205.7° C. (intermediate 150).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customThe whole was evaporated
  3. additionwater was added to the residue
  4. extractionThe product was extracted three times with 4-methyl-2-pentanone
  5. customThe combined extracts were dried
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by column chromatography over silica gel using
  9. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  10. customThe pure fractions were collected
  11. customthe eluent was evaporated
  12. customThe residue was crystallized from 4-methyl-2-pentanone

Sources & evidence

ORD record
ord-5a0092febdd5469e8bbd596001994a0e
Source dataset
uspto-grants-1989_12
Patent number
US04888426

Reaction notes

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