Piperidine → HCID 71015365, compound

HRID 716068Notes

Reaction equation

HRID 716068 reaction equation
[C:1]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([NH:16][C:17]3[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=3)[N:14]=2)[N:9]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:8]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[N:33]1([CH2:38][C:39]#[N:40])[CH:37]=[N:36][CH:35]=[N:34]1.N1CCCCC1.C(OCC)(=O)C.CCCCCC>C(O)C>[C:1]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([NH:16][C:17]3[CH:18]=[CH:19][C:20]([CH:21]=[C:38]([N:33]4[CH:37]=[N:36][CH:35]=[N:34]4)[C:39]#[N:40])=[CH:23][CH:24]=3)[N:14]=2)[N:9]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:30])[CH3:31])[CH:8]=1)(=[O:6])[C:2]([CH3:3])([CH3:4])[CH3:5]

Participants

6

Reactant 4

HCID 8082PiperidineHCID 27648382-(1H-1,2,4-triazol-1-yl)acetonitrileHCID 21226206Ethyl acetate hexaneHCID 867121234-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)benzaldehyde

Product 1

HCID 71015365HCID 71015365, compoundYield 43.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a 50 ml three necked round bottom flask, 4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)-methyl)-5H-pyrrolo[2,3-b]pyrazine-2-ylamino)benzaldehyde (0.1 g, 0.22 mmole) and 2-(1H-1,2,4-triazol-1-yl)acetonitrile (0.0716 g, 0.66 mmole) was taken in ethanol (5 mL). To this reaction mixture, piperidine (0.2 mL) was added drop wise at RT. After completion of the addition, the reaction mass was refluxed for 16 hrs and the completion of the reaction was monitored on TLC using ethyl acetate:hexane (5:5) as a mobile phase. After completion of the reaction, ethanol was distilled out and water was added to residue. Aqueous was extracted with ethyl acetate, organic layers were combined, dried over Na2SO4, filtered and concentrated to afford crude product. The crude compound was purified using column purification by eluting the compound with 40% ethyl acetate in hexanes triturated with n-pentane, pentane layer was decanted and solid was dried under vacuum to yield 0.052 g of 3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)-2-(1H-1,2,4-triazol-1-yl)acrylonitrile.

Workup

  1. additionAfter completion of the addition
  2. temperaturethe reaction mass was refluxed for 16 hrs
  3. distillationwas distilled out and water
  4. additionwas added to residue
  5. extractionAqueous was extracted with ethyl acetate, organic layers
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford crude product
  10. customThe crude compound was purified
  11. customcolumn purification
  12. washby eluting the compound with 40% ethyl acetate in hexanes
  13. customtriturated with n-pentane, pentane layer
  14. customwas decanted
  15. customsolid was dried under vacuum

Sources & evidence

ORD record
ord-d1c86bb256144f508255fbadcd757ee6
Source dataset
uspto-grants-2015_11
Patent number
US09187487B2

Reaction notes

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