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

HRID 2248799ノート

反応式

HRID 2248799 の反応式
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

参加物

4

反応物 3

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

生成物 1

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

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-d9c054a23ec34b78962549eaf978de95
出典データセット
uspto-grants-1991_08
特許番号
US05041448

反応ノート

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