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

HRID 716036Notes

Reaction equation

HRID 716036 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].[O:33]1[CH2:38][CH2:37][N:36]([C:39](=[O:43])[CH2:40][C:41]#[N:42])[CH2:35][CH2:34]1.C(O)(=O)C.N1CCCCC1>C(O)C>[N:36]1([C:39]([C:40](=[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:41]#[N:42])=[O:43])[CH2:37][CH2:38][O:33][CH2:34][CH2:35]1

Participants

5

Reactant 3

HCID 2292794-(Cyanoacetyl)morpholineHCID 9793820Piperidine, acetateHCID 867121234-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)benzaldehyde

Product 1

HCID 779816212-(morpholine-4-carbonyl)-3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)-methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylonitrileYield 55.6%

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]pyrazin-2-ylamino)benzaldehyde (0.25 g, 0.00055 mole) and 3-morpholino-3-oxopropanenitrile (0.34 g, 0.0022 mole) was taken in ethanol (20 ml). To this reaction mixture, piperidine acetate (1.0 ml) was added drop wise at RT. After completion of the addition, reaction mixture was refluxed for 4 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 using column purification by eluting the compound with 40-50% ethyl acetate in hexanes to yield 0.18 g of 2-(morpholine-4-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 using the procedure described in Example 1, Step 2 above.

Workup

  1. additionAfter completion of the addition, reaction mixture
  2. temperaturewas refluxed for 4 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. customcolumn purification
  12. washby eluting the compound with 40-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c6594fc6dfc54d359911f7bd63c14bcc
Source dataset
uspto-grants-2015_11
Patent number
US09187487B2

Reaction notes

Loading…