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

HRID 716034Notes

Reaction equation

HRID 716034 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]([NH:38][CH3:39])=[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]([NH:38][CH3:39])=[O:37])#[N:34]

Participants

5

Reactant 3

HCID 806222-Cyano-N-methylacetamideHCID 9793820Piperidine, acetateHCID 867121234-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)benzaldehyde

Product 1

HCID 779816132-cyano-N-methyl-3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylamideYield 95.7%

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]pyrazin-2-ylamino)benzaldehyde (0.25 g, 0.0005 mole) and 2-cyano-N-methylacetamide (0.22 g, 0.0022 mole) was taken in ethanol (20 ml). To this reaction mixture, piperidine acetate (1.0 ml) was added dropwise at RT. After completion of the addition, reaction mixture was refluxed for 2 hr. After completion of the reaction, ethanol was distilled out under vacuum and water was added to the residue. The aq. layer was extracted with ethyl acetate. Combined organic layer was dried over Na2SO4, filtered and concentrated to afford crude product. The crude compound was purified by triturated with n-pentane, the pentane layer was decanted and solid was dried under vacuum to yield 0.255 g of 2-cyano-N-methyl-3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylamide which was converted to the title compound as described in Example 1, Step 2 above.

Workup

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

Sources & evidence

ORD record
ord-dd029958a1594611b1cc8d41a3911bed
Source dataset
uspto-grants-2015_11
Patent number
US09187487B2

Reaction notes

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