Phosphorus oxychloride → 6-chloro-9-[(4-fluorophenyl)methyl]-8-[[1-(phenylmethyl)-4-piperidinyl]methyl]-9H-purine

HRID 256646Notes

Reaction equation

HRID 256646 reaction equation
Cl.[C:2]1([CH2:8][N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][C:16](O)=O)[CH2:11][CH2:10]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:19][C:20]1[N:25]=[CH:24][N:23]=[C:22]([NH:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[C:21]=1[NH2:35].P(Cl)(Cl)(Cl)=O>>[Cl:19][C:20]1[N:25]=[CH:24][N:23]=[C:22]2[C:21]=1[N:35]=[C:16]([CH2:15][CH:12]1[CH2:13][CH2:14][N:9]([CH2:8][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:10][CH2:11]1)[N:26]2[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 140128442-(1-Benzylpiperidin-4-yl)acetic acid hydrochlorideHCID 140224096-chloro-N4-(4-fluorobenzyl)pyrimidine-4,5-diamine

Product 1

HCID 197852696-chloro-9-[(4-fluorophenyl)methyl]-8-[[1-(phenylmethyl)-4-piperidinyl]methyl]-9H-purineYield 75%

Procedure

A mixture of 20.65 parts of 1-(phenylmethyl)-4-piperidineacetic acid hydrochloride, 19.5 parts of 6-chloro-N4 -[(4-fluorophenyl)methyl]-4,5-pyrimidinediamine and 510 parts of phosphoryl chloride was stirred and refluxed for 13 hours. The reaction mixture was evaporated. The residue was poured into ice water. The whole was treated with sodium hydroxide. The product was extracted with 4-methyl-2-pentanone. The extract was washed with water, 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 first fraction was collected and the eluent was evaporated, yielding 23.6 parts (75%) of 6-chloro-9-[(4-fluorophenyl)methyl]-8-[[1-(phenylmethyl)-4-piperidinyl]-methyl]-9H-purine as an oily residue (compound 1).

Workup

  1. temperaturerefluxed for 13 hours
  2. customThe reaction mixture was evaporated
  3. additionThe residue was poured into ice water
  4. additionThe whole was treated with sodium hydroxide
  5. extractionThe product was extracted with 4-methyl-2-pentanone
  6. washThe extract was washed with water
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by column chromatography over silica gel using
  11. additiona mixture of trichloromethane and methanol
  12. customThe first fraction was collected
  13. customthe eluent was evaporated

Sources & evidence

ORD record
ord-96245a677c934246acda97af312737b7
Source dataset
uspto-grants-1993_11
Patent number
US05258380

Reaction notes

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