Potassium Carbonate → 799557-88-3

HRID 734346Notes

Reaction equation

HRID 734346 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[CH:21][N:20]=1.C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])O.[Na+]>CS(C)=O.CCOC(C)=O>[ClH:18].[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([CH:12]2[CH2:13][CH2:14][N:15]([C:19]3[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[CH:21][N:20]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 282821951-Isopropyl-4-(piperidine-4-carbonyl)-piperazine

Product 1

HCID 68817996799557-88-3Yield 39.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To 1-isopropyl-4-(piperidine4-carbonyl)-piperazine (0.239 g)(D1) and 2-chloro-5-cyano-pyridine (0.138 g), dissolved in DMSO (5 ml), was added potassium carbonate (0.14 g). The reaction was heated to 80° C. for 4 h before cooling and dilution with saturated sodium hydrogen carbonate (50 ml) and EtOAc (80 ml). The EtOAc layer was washed further with brine (3×80 ml) and then extracted with 1N HCl. The aqueous HCl extract was basified and back-extracted with EtOAc which was concentrated under vacuum. A solution of 2N HCl in diethyl ether (1 ml) was then added and the precipitate filtered and washed with diethyl ether. Crystallisation from methanol afforded the title compound (E1)(0.15 g). 1H NMR δ [DMSO-d6]:1.29 (6H, d, J=6.4 Hz), 1.4-1.6 (2H, m), 1.7-1.85 (2H, m), 2.8-3.27 (6H, m), 3.32-3.62 (3H, m), 3.69 (1H, m), 4.24 (1H, brd, J=13 Hz), 4.35-4.55 (3H, m), 6.96 (1H, d, J=9.1 Hz), 7.84 (1H, dd, J=9.1Hz and 1.5 Hz), 8.47 (1H, d, J=1.5 Hz) and 11.36 (1H, brs). MS electrospray; (+ve ion) 342 (MH+).

Workup

  1. temperaturebefore cooling
  2. washThe EtOAc layer was washed further with brine (3×80 ml)
  3. extractionextracted with 1N HCl
  4. extractionThe aqueous HCl extract
  5. extractionback-extracted with EtOAc which
  6. concentrationwas concentrated under vacuum
  7. additionA solution of 2N HCl in diethyl ether (1 ml) was then added
  8. filtrationthe precipitate filtered
  9. washwashed with diethyl ether
  10. customCrystallisation from methanol

Sources & evidence

ORD record
ord-eef5cd896ae542688a5745cf2f88775e
Source dataset
uspto-grants-2009_09
Patent number
US07592347B2

Reaction notes

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