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Trifluoroacetic acid → 6-[2-(2-Oxopiperazin-1-yl)ethyl]pyridine-3-carbonitrile

HRID 1466050
Notes
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Reaction equation

HRID 1466050 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][NH:11][CH2:12][CH2:13][NH:14][C:15](=O)OC(C)(C)C)=[N:7][CH:8]=1)#[N:2].ClC[C:24](Cl)=[O:25].C(O)(C(F)(F)F)=O>C(Cl)Cl>[O:25]=[C:24]1[CH2:15][NH:14][CH2:13][CH2:12][N:11]1[CH2:10][CH2:9][C:6]1[N:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 6577Chloroacetyl chlorideHCID 121005078tert-Butyl (2-{[2-(5-cyanopyridin-2-yl)ethyl]amino}ethyl)carbamate

Product 1

HCID 895247896-[2-(2-Oxopiperazin-1-yl)ethyl]pyridine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

TEA (1 eq) was added dropwise to a solution of tert-Butyl (2-{[2-(5-cyanopyridin-2-yl)ethyl]amino}ethyl)carbamate (1 eq) and chloroacetyl chloride (1 eq) in 200 mL of DCM at 0° C. The mixture was stirred at room temperature for 30 minutes and washed with water and brine, dried over anhydrous Na2SO4 and condensed under vacuum. The resulting solid (1.0 g, 2.7 mmol) was added to the mixture of 10 mL TFA and 10 mL of DCM and stirred at RT for 1 hour then concentrated by vacuum. The residue was re-dissolved in CH3CN, K2CO3 was added and the mixture was stirred at RT for 2 hours. The mixture was poured into water and extracted with EtOAc twice. The combined organic layers were concentrated and the residue was purified by flash chromatography (DCM:MeOH=10:1) to afford the title compound 1H-NMR (400 MHz, CDCl3) δ ppm 8.74 (d, J=1.6 Hz, 1H), 7.81-7.83 (m, 1H), 7.31 (d, J=8.0 Hz, 1H), 3.71 (t, J=7.2 Hz, 2H), 3.42 (d, J=7.2 Hz, 2H), 3.24 (t, J=5.6 Hz, 2H), 3.09 (t, J=7.2 Hz, 2H), 2.98 (t, J=5.6 Hz, 2H).

Workup

  1. washwashed with water and brine
  2. dry with materialdried over anhydrous Na2SO4 and condensed under vacuum
  3. stirringstirred at RT for 1 hour
  4. concentrationthen concentrated by vacuum
  5. dissolutionThe residue was re-dissolved in CH3CN
  6. additionK2CO3 was added
  7. stirringthe mixture was stirred at RT for 2 hours
  8. additionThe mixture was poured into water
  9. extractionextracted with EtOAc twice
  10. concentrationThe combined organic layers were concentrated
  11. customthe residue was purified by flash chromatography (DCM:MeOH=10:1)

Sources & evidence

ORD record
ord-26792eb4f3b44751b79f7e7510341d7b
Source dataset
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08999990B2

Reaction notes

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