Cyanoacetamide → 2-cyano-3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylamide

HRID 716032Notes

Reaction equation

HRID 716032 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].[C:33]([CH2:35][C:36]([NH2:38])=[O:37])#[N:34].C(O)(=O)C.N1CCCCC1>C(O)C>[C:33]([C:35](=[CH:21][C:20]1[CH:23]=[CH:24][C:17]([NH:16][C:13]2[N:14]=[C:15]3[C:7]([C:1](=[O:6])[C:2]([CH3:5])([CH3:3])[CH3:4])=[CH:8][N:9]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:10]3=[N:11][CH:12]=2)=[CH:18][CH:19]=1)[C:36]([NH2:38])=[O:37])#[N:34]

Participants

5

Reactant 3

HCID 7898CyanoacetamideHCID 9793820Piperidine, acetateHCID 867121234-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)benzaldehyde

Product 1

HCID 710142392-cyano-3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylamideYield 96.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a 50 ml three necked round bottom flask 4-(7-pivaloyl-5-((2-(trimethylsilyl)-ethoxy)-methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)benzaldehyde (0.25 g, 0.0005 mole) and 2-cyanoacetamide (0.094 g, 0.0011 mole) was taken in ethanol (20 ml). To this reaction mixture, piperidine acetate (3.3 M solution in water) (1.0 ml) was added drop wise at RT. After completion of the addition, reaction mixture was refluxed for 2 hr. After completion of the reaction, the ethanol was distilled out and water was added to residue. The aq. layer was extracted with ethyl acetate, the organic layers were combined, dried over Na2SO4, filtered and concentrated to afford crude product. The crude compound was purified by triturated with n-pentane, pentane layer was decanted and solid was dried under vacuum to yield 0.25 g of 2-cyano-3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)-methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylamide.

Workup

  1. additionAfter completion of the addition, reaction mixture
  2. temperaturewas refluxed for 2 hr
  3. customAfter completion of the reaction
  4. distillationthe ethanol was distilled out and water
  5. additionwas added to residue
  6. extractionThe aq. layer was extracted with ethyl acetate
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford crude product
  11. customThe crude compound was purified
  12. customby triturated with n-pentane, pentane layer
  13. customwas decanted
  14. customsolid was dried under vacuum

Sources & evidence

ORD record
ord-1d42c67dd5af4bdf8997376efd5f7bfc
Source dataset
uspto-grants-2015_11
Patent number
US09187487B2

Reaction notes

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