Piperidine → HCID 57677479, compound

HRID 492701Notes

Reaction equation

HRID 492701 reaction equation
[NH2:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH2:13])[CH:8]=2)=[CH:4][C:3]=1[Cl:16].C(N(CC)CC)C.Cl[C:25](OC1C=CC=CC=1)=[O:26].[NH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>O1CCCC1.C(OCC)C.CN(C)C=O>[NH2:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:25]([N:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)=[O:26])[CH:8]=2)=[CH:4][C:3]=1[Cl:16]

Participants

8

Reactant 4

HCID 8082PiperidineHCID 8471Triethylamine2×HCID 15891Phenyl chloroformate2×HCID 229367984-(4-Amino-3-chlorophenoxy)pyridin-2-ylamine

Product 1

HCID 57677479HCID 57677479, compoundYield 41.9%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-(4-Amino-3-chlorophenoxy)pyridin-2-ylamine (750 mg, 3.18 mmol) was dissolved in tetrahydrofuran (30 ml), and then triethylamine (0.444 ml, 4.77 mmol) was added thereto. Phenyl chloroformate (0.399 ml, 4.77 mmol) was added dropwise thereto while ice-cooling, followed by stirring at room temperature for 3.5 hrs. Triethylamine (0.444 ml) and phenyl chloroformate (0.399 ml) were further added thereto while ice-cooling, followed by stirring for 15 min. N,N-dimethylformamide (6.0 ml) and piperidine (1.5 ml) were added thereto, followed by stirring at room temperature for 5.5 hrs. The reaction mixture was concentrated under a reduced pressure, and then N,N-dimethylformamide (4.0 ml) and piperidine (1.0 ml) were added thereto, followed by stirring at room temperature for 36 hrs. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:1 to 1:2, ethyl acetate, then ethyl acetate:methanol=10:1). Fractions containing the target compound were concentrated to give a solid, which was suspended in diethyl ether, filtered, and dried under aeration to provide the titled compound (462 mg, 1.33 mmol, 41.9%) as a pale yellow solid.

Workup

  1. temperaturewhile ice-cooling
  2. temperaturewhile ice-cooling
  3. stirringby stirring for 15 min
  4. stirringby stirring at room temperature for 5.5 hrs
  5. concentrationThe reaction mixture was concentrated under a reduced pressure
  6. additionN,N-dimethylformamide (4.0 ml) and piperidine (1.0 ml) were added
  7. stirringby stirring at room temperature for 36 hrs
  8. customThe reaction mixture was partitioned between ethyl acetate and water
  9. washThe organic layer was washed with brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. customThe solvent was evaporated
  12. customto give a residue, which
  13. customwas then purified by silica gel column chromatography (eluent
  14. additionFractions containing the target compound
  15. concentrationwere concentrated
  16. customto give a solid, which
  17. filtrationfiltered
  18. customdried under aeration

Sources & evidence

ORD record
ord-576f50153be24846af6b342acb742ccb
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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