Phosphorus oxychloride → N-[4-[[(4-fluorophenyl)methyl]amino]-5-pyrimidinyl]-1-(phenylmethyl)-4-piperidineacetamide

HRID 256643Notes

Reaction equation

HRID 256643 reaction equation
Cl.[C:2]1([CH2:8][N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][C:16]([OH:18])=O)[CH2:11][CH2:10]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][NH:27][C:28]2[C:33]([NH2:34])=[CH:32][N:31]=[CH:30][N:29]=2)=[CH:22][CH:21]=1.P(Cl)(Cl)(Cl)=O>>[F:19][C:20]1[CH:21]=[CH:22][C:23]([CH2:26][NH:27][C:28]2[C:33]([NH:34][C:16](=[O:18])[CH2:15][CH:12]3[CH2:11][CH2:10][N:9]([CH2:8][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[CH2:14][CH2:13]3)=[CH:32][N:31]=[CH:30][N:29]=2)=[CH:24][CH:25]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 140128442-(1-Benzylpiperidin-4-yl)acetic acid hydrochlorideHCID 70462412N4-[(4-fluorophenyl)methyl]-4,5-pyrimidinediamine

Product 1

HCID 19785306N-[4-[[(4-fluorophenyl)methyl]amino]-5-pyrimidinyl]-1-(phenylmethyl)-4-piperidineacetamideYield 61%

Procedure

A mixture of 52.4 parts of 1-(phenylmethyl)-4-piperidineacetic acid hydrochloride, 38.7 parts of N4 -[(4-fluorophenyl)methyl]- 4,5-pyrimidinediamine and 765 parts of phosphoryl chloride was stirred and refluxed for 30 minutes. The reaction mixture was evaporated. The residue was decomposed with ice water. The product was extracted with dichloromethane after treatment with sodium hydroxide. 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, (95:5 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 37 parts (61%) of N-[4-[[(4-fluorophenyl)methyl]amino]-5-pyrimidinyl]-1-(phenylmethyl)-4-piperidineacetamide; mp. 157.3° C. (interm. 45).

Workup

  1. temperaturerefluxed for 30 minutes
  2. customThe reaction mixture was evaporated
  3. extractionThe product was extracted with dichloromethane after treatment with sodium hydroxide
  4. washThe extract was washed with water
  5. customdried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography over silica gel using
  9. additiona mixture of trichloromethane and methanol
  10. customThe pure fractions were collected
  11. customthe eluent was evaporated
  12. customThe residue was crystallized from acetonitrile
  13. filtrationThe product was filtered off
  14. customdried

Sources & evidence

ORD record
ord-e9400efbe6e14a7fb1fdc8c9de7d7020
Source dataset
uspto-grants-1993_11
Patent number
US05258380

Reaction notes

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