Phosphorus oxychloride → 9-[(4-fluorophenyl)methyl]-8-[[1-(phenylmethyl)-4-piperidinyl]methyl]-9H-purine

HRID 256647Notes

Reaction equation

HRID 256647 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]2[C:15]([NH:16][C:17](=O)[CH2:18][CH:19]3[CH2:24][CH2:23][N:22]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH2:21][CH2:20]3)=[CH:14][N:13]=[CH:12][N:11]=2)=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:17]([CH2:18][CH:19]3[CH2:24][CH2:23][N:22]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH2:21][CH2:20]3)=[N:16][C:15]3[C:10]2=[N:11][CH:12]=[N:13][CH:14]=3)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 19785306N-[4-[[(4-fluorophenyl)methyl]amino]-5-pyrimidinyl]-1-(phenylmethyl)-4-piperidineacetamide

Product 1

HCID 197852669-[(4-fluorophenyl)methyl]-8-[[1-(phenylmethyl)-4-piperidinyl]methyl]-9H-purineYield 30.4%

Procedure

A mixture of 36 parts of N-[4-[[(4-fluorophenyl)methyl]amino]-5-pyrimidinyl]-1-(phenylmethyl}-4-piperidineacetamide and 935 parts of phosphoryl chloride was stirred and refluxed for 8 hours. After cooling, the reaction mixture was evaporated. The residue was decomposed in ice water. The whole was treated with a sodium hydroxide solution. 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, (97:3 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was stirred in 2,2'-oxybispropane. The product was filtered off and crystallized from acetonitrile. The product was filtered off and dried, yielding 10.6 parts (30.4%) of 9-[(4-fluorophenyl)methyl]-8-[[1-(phenylmethyl)-4-piperidinyl]methyl]-9H-purine; mp. 136.4° C. (compound 4).

Workup

  1. temperaturerefluxed for 8 hours
  2. temperatureAfter cooling
  3. customthe reaction mixture was evaporated
  4. additionThe whole was treated with a sodium hydroxide solution
  5. extractionThe product was extracted with 4-methyl-2-pentanone
  6. customThe extract was dried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column chromatography over silica gel using
  10. additiona mixture of trichloromethane and methanol
  11. customThe pure fractions were collected
  12. customthe eluent was evaporated
  13. stirringThe residue was stirred in 2,2'-oxybispropane
  14. filtrationThe product was filtered off
  15. customcrystallized from acetonitrile
  16. filtrationThe product was filtered off
  17. customdried

Sources & evidence

ORD record
ord-be51f5a9a6cc4b90bf20c10538fe98b6
Source dataset
uspto-grants-1993_11
Patent number
US05258380

Reaction notes

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