Piperidine, acetate → 2-(azetidine-1-carbonyl)-3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)-methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylonitrile

HRID 716035Notes

Reaction equation

HRID 716035 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([C:37](=[O:41])[CH2:38][C:39]#[N:40])[CH2:36][CH2:35][CH2:34]1.C(O)(=O)C.N1CCCCC1>C(O)C>[N:33]1([C:37]([C:38](=[CH:21][C:20]2[CH:23]=[CH:24][C:17]([NH:16][C:13]3[N:14]=[C:15]4[C:7]([C:1](=[O:6])[C:2]([CH3:4])([CH3:3])[CH3:5])=[CH:8][N:9]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:31])([CH3:30])[CH3:32])[C:10]4=[N:11][CH:12]=3)=[CH:18][CH:19]=2)[C:39]#[N:40])=[O:41])[CH2:36][CH2:35][CH2:34]1

Participants

5

Reactant 3

HCID 9793820Piperidine, acetateHCID 450871943-(Azetidin-1-yl)-3-oxopropanenitrileHCID 867121234-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)benzaldehyde

Product 1

HCID 867121242-(azetidine-1-carbonyl)-3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)-methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylonitrileYield 86.4%

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 (0.13 g, 0.00029 mole) and 3-(azetidin-1-yl)-3-oxopropanenitrile (0.107 g, 0.00086 mole) was taken in ethanol (20 ml). To this reaction mixture, piperidine acetate (0.05 ml) was added drop wise at RT. After completion of the addition, the 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 and the combined organic layer was 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 0.14 g of 2-(azetidine-1-carbonyl)-3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)-methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylonitrile which was converted to the title compound as described in Example 1, Step 2.

Workup

  1. additionAfter completion of the addition
  2. temperaturethe reaction mixture was 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 materialthe combined 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, pentane layer
  12. customwas decanted
  13. customsolid was dried under vacuum

Sources & evidence

ORD record
ord-dcc9e1e61f1b42c4b87766ea4c43e682
Source dataset
uspto-grants-2015_11
Patent number
US09187487B2

Reaction notes

Loading…