1,2-Dichloroethane → HCID 21193132, compound

HRID 1068224Notes

Reaction equation

HRID 1068224 reaction equation
[NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1.[C:9]([N:12]1[CH2:17][CH2:16][CH:15]([C:18](O)=O)[CH2:14][CH2:13]1)(=[O:11])[CH3:10].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[OH-].[NH4+]>C(Cl)Cl.O>[CH:2]1[N:1]=[C:18]([CH:15]2[CH2:16][CH2:17][N:12]([C:9](=[O:11])[CH3:10])[CH2:13][CH2:14]2)[N:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=12

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 14923Ammonium HydroxideHCID 195092-PyridinemethanamineHCID 757711-HydroxybenzotriazoleHCID 1172551-Acetylpiperidine-4-carboxylic acid

Product 1

HCID 21193132HCID 21193132, compoundYield 10.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-(aminomethyl)pyridine (3.17 g, 29.3 mmol), 1-acetylpiperidine-4-carboxylic acid (5.02 g, 29.3 mmol) and HOBT (4.78 g, 35.2 mmol) in 30 mL of CH2Cl2 was added EDC (8.43 g, 44.0 mmol) at rt. After stirring at rt overnight, the reaction mixture was diluted with methylene chloride and washed with aqueous sodium bicarbonate followed by brine. The organic phase was dried over anhydrous MgSO4. Concentration under reduced pressure afforded a viscous oil, which was dissolved in polyphosphoric acid (5 mL). The mixture was heated at ˜120° C. for 18 h. After cooling to rt, the syrup was poured onto ice and water was added to keep the solution temperature below 10° C. The resulting dark brown solution was basified with ammonium hydroxide. Aqueous layer was extracted with EtOAC (3×). The combined organic phase was washed with brine and dried over anhydrous MgSO4. Concentration under reduced pressure afforded 761 mg of the title compound as a viscous oil. 1H NMR (400 MHz, CDCl3): δ 1.80˜2.20 (m, 6H), 2.88˜2.95 (m, 1H), 3.30˜3.34 (m, 2H), 4.00˜4.04 (br d, 1H), 4.62˜4.65 (br d, 1H), 6.58 (dt, J=6.8, 1.1 Hz, 1H), 6.68 (dt, J=6.4, 0.7 Hz, 1H), 7.38 (s, 1H), 7.44 (d, J=9.2 Hz, 1H), 7.79 (dd, J=7.3, 0.8 Hz, 1H).

Workup

  1. washwashed with aqueous sodium bicarbonate
  2. dry with materialThe organic phase was dried over anhydrous MgSO4
  3. concentrationConcentration under reduced pressure
  4. customafforded a viscous oil, which
  5. temperatureThe mixture was heated at ˜120° C. for 18 h
  6. temperatureAfter cooling to rt
  7. additionwas added
  8. customthe solution temperature below 10° C
  9. extractionAqueous layer was extracted with EtOAC (3×)
  10. washThe combined organic phase was washed with brine
  11. dry with materialdried over anhydrous MgSO4
  12. concentrationConcentration under reduced pressure

Sources & evidence

ORD record
ord-f0789333f34d44fa9d2b347ffed8d4f9
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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