4-Aminopyridine → HCID 21101797, compound

HRID 1353377Notes

Reaction equation

HRID 1353377 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.Cl[C:9](OC1C=CC([N+]([O-])=O)=CC=1)=[O:10].C(N(C(C)C)CC)(C)C.[Cl:30][C:31]1[CH:40]=[C:39]2[C:34]([C:35]([N:41]3[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]3)=[CH:36][CH:37]=[N:38]2)=[CH:33][CH:32]=1>ClCCl.CCOC(C)=O>[Cl:30][C:31]1[CH:40]=[C:39]2[C:34]([C:35]([N:41]3[CH2:46][CH2:45][N:44]([C:9]([NH:1][C:2]4[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=4)=[O:10])[CH2:43][CH2:42]3)=[CH:36][CH:37]=[N:38]2)=[CH:33][CH:32]=1

Participants

7

Reactant 4

HCID 17274-AminopyridineHCID 81531Diisopropylethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 7383897-Chloro-4-(piperazin-1-yl)quinoline

Product 1

HCID 21101797HCID 21101797, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

At 0° C. under nitrogen, to a solution of 4-aminopyridine (114 mg, 1.21 mmol) and 4-nitrophenyl chloroformate (244 mg, 1.21 mmol) in dichloromethane (5 mL) is added diisopropyl(ethyl)amine dropwise (391 mg, 3.03 mmol). After 10 min, the ice bath is removed, and the reaction mixture is stirred at rt. for an additional hour. After removal of solvent under vacuum, EtOAc (5 mL), diisopropyl(ethyl)amine (261 mg, 2.02 mmol) and 7-chloro-4-(piperazin-1-yl)quinoline (250 mg, 1.01 mmol) are added. The resulting mixture is kept at reflux for about 5 hr, then cooled to rt, diluted with EtOAc (10 mL), and quenched with saturated sodium bicarbonate (5 mL). The aqueous solution is extracted with EtOAc (2×10 mL), and the combined organic phase is washed with brine (10 mL) and dried over sodium sulfate. Removal of solvent followed by purification through flash chromatography with CH2Cl2-MeOH affords the title product.

Workup

  1. customthe ice bath is removed
  2. waitfor an additional hour
  3. additionare added
  4. temperatureat reflux for about 5 hr
  5. temperaturecooled to rt
  6. customquenched with saturated sodium bicarbonate (5 mL)
  7. extractionThe aqueous solution is extracted with EtOAc (2×10 mL)
  8. washthe combined organic phase is washed with brine (10 mL)
  9. dry with materialdried over sodium sulfate
  10. customRemoval of solvent
  11. customfollowed by purification through flash chromatography with CH2Cl2-MeOH

Sources & evidence

ORD record
ord-b23c0cc5ae1744a287170674b444c6ec
Source dataset
uspto-grants-2007_05
Patent number
US07220856B2

Reaction notes

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