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

HRID 716037Notes

Reaction equation

HRID 716037 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].[CH3:33][N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.[O:40]=[CH:41][CH2:42][C:43]#[N:44].C(O)(=O)C.N1CCCCC1>C(O)C>[CH3:33][N:34]1[CH2:39][CH2:38][N:37]([C:41]([C:42](=[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]([CH3:32])([CH3:30])[CH3:31])[C:10]4=[N:11][CH:12]=3)=[CH:18][CH:19]=2)[C:43]#[N:44])=[O:40])[CH2:36][CH2:35]1

Participants

5

Reactant 3

HCID 9793820Piperidine, acetateHCID 867121234-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)benzaldehydeHCID 867121254-Methylpiperazin 3-oxopropanenitrile

Product 1

HCID 710144592-(4-methylpiperazine-1-carbonyl)-3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylonitrileYield 103.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
80 °C

Procedure

To a 35 ml reaction vial, 4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)benzaldehyde (0.200 g, 0.0004 mole) and 3-(4-methylpiperazin-3-oxopropanenitrile (0.211 g, 0.0013 mole) was taken in ethanol (10 ml). To this, piperidine acetate (3.3 M solution in water) (3 ml, 0.0099 mole) was added at RT and the reaction mixture was heated to 80° C. for 16 hr. After completion of the reaction, ethanol was evaporated under reduced pressure from the reaction mixture and then diluted with EtOAc (20 ml). The organic layer was washed with water, dried over Na2SO4 and evaporated to get product which was subjected for the column purification. The crude compound was purified using column purification using 60-120 mesh size neutral silica by eluting the compound with 2% MeOH in CH2Cl2 to yield 0.25 g of 2-(4-methylpiperazine-1-carbonyl)-3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylonitrile.

Workup

  1. customTo a 35 ml reaction vial
  2. customwas evaporated under reduced pressure from the reaction mixture
  3. additiondiluted with EtOAc (20 ml)
  4. washThe organic layer was washed with water
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customto get product which
  8. customwas subjected for the column purification
  9. customThe crude compound was purified
  10. customcolumn purification
  11. washby eluting the compound with 2% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-579a979da01c443cb08cdeb4b0eff2bb
Source dataset
uspto-grants-2015_11
Patent number
US09187487B2

Reaction notes

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