Piperazine → HCID 40715854, compound

HRID 1619202Notes

Reaction equation

HRID 1619202 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1C(O)=O.C1C=[CH:13][C:14]2N(O)N=[N:17][C:15]=2C=1.C[CH2:22][N:23]([CH:27](C)C)[CH:24](C)C.[NH:30]1CCNCC1.[CH3:36][N:37]([CH:39]=[O:40])[CH3:38]>C(OCC)(=O)C.O>[Cl:1][C:2]1[N:10]=[CH:9][C:8]([C:39]([N:37]2[CH2:38][CH2:24][N:23]([C:22]3[N:17]=[CH:15][CH:14]=[CH:13][N:30]=3)[CH2:27][CH2:36]2)=[O:40])=[CH:7][CH:3]=1

Participants

8

Reactant 5

HCID 4837PiperazineHCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 762582-Chloronicotinic acidHCID 81531Diisopropylethylamine

Product 1

HCID 40715854HCID 40715854, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of chloronicotinic acid (2.51 g, 15.9 mmol) in DMF (64 ml), EDO (4.57 g, 23.9 mmol) and HOBt (3.23 g, 23.9 mmol) were added. Hunig's base (19.3 ml, 111 mmol) was added and the reaction was allowed to stir for 5 minutes. After this induction period, piperazine (4.52 g, 19.1 mmol) was added and the reaction stirred at room temperature. After stirring for 72 hours, the reaction was diluted with ethyl acetate and water. The layers were separated, and the aqueous portion was extracted twice more with ethyl acetate. The combined organic layers were washed with water three times and once with brine, dried over MgSO4, filtered, and concentrated. The crude product was purified by silica gel chromatography using 20-25% acetone/hexanes, yielding the product (2.05 g, 42%) as a tan solid: 1H NMR (400 MHz, CDCl3) δ 8.49 (d, J=1.8 Hz, 1H), 8.34 (d, J=4.7 Hz, 2H), 7.77 (dd, J=8.2, 2.4 Hz, 1H), 7.43 (d, J=8.1 Hz, 1H), 6.57 (t, J=4.8 Hz, 1H), 3.89 (bs, 6H), 3.52 (bs, 2H); m/z calcd. for C14H14ClN5O: 303.08 found: (M+H)+304.1; HPLC retention time=1.822 min (gradient of solvent B-0 to 100%; wavelength 254 nm), purity=100%.

Workup

  1. stirringthe reaction stirred at room temperature
  2. stirringAfter stirring for 72 hours
  3. customThe layers were separated
  4. extractionthe aqueous portion was extracted twice more with ethyl acetate
  5. washThe combined organic layers were washed with water three times and once with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-d832ee7544a84c589518aff5c1fa1056
Source dataset
uspto-grants-2014_07
Patent number
US08772291B2

Reaction notes

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