Pyridine → HCID 178508400, compound

HRID 1752806Notes

Reaction equation

HRID 1752806 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:16][CH2:17][OH:18])[CH2:9][CH2:10][CH2:11][C:12](OC)=O)=[CH:4][CH:3]=1.C(=O)(O)O.[NH2:23][NH:24][C:25]([NH2:27])=[NH:26].N1C=CC=CC=1>C(Cl)(Cl)Cl.CO.C(O)(=O)C>[NH2:27][C:25]1[NH:24][N:23]=[C:12]([CH2:11][CH2:10][CH2:9][N:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:16][CH2:17][OH:18])[N:26]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 86719322HCID 86719322, compoundHCID 178513185HCID 178513185, compound2×

Product 1

HCID 178508400HCID 178508400, compoundYield 45.7%

Reagents, catalysts & solvents 1

HCID 21866353chloroform methanol HOAcSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of methyl 4-[(4-fluorophenyl)(2-hydroxyethyl)amino]butanoate (1.1 g, 4.31 mmol), aminoguanidine bicarbonate (1.47 g, 10.78 mmol), and pyridine (12 mL) was added to a 200 mL RBF with a magnetic stirring bar. The flask was fitted with a condenser and heated to 125° C. using an oil bath. Progress of the reaction was monitored by TLC using chloroform:methanol: acetic acid (9:1:0.2) (Rf starting material=0.8, Rf product=0.1). During the course of heating, additional portions of aminoguanidine bicarbonate were added at 15 h and 22 h (2×1.0 g, 14.7 mmol total). After 37 hours of heating, the reaction was complete by TLC analysis and was allowed to cool to ambient temperature. The mixture was concentrated under reduced pressure and partitioned between ethyl acetate (60 mL) and water (30 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with saturated aqueous NaCl (10 mL), dried (Na2SO4), filtered and concentrated. The crude material was purified by silica gel column chromatography using 100% ethyl acetate, followed by 10% methanol in dichloromethane to afford the title compound as an oil (0.55 g, 45% yield).

Workup

  1. additionwas added to a 200 mL RBF with a magnetic stirring bar
  2. customThe flask was fitted with a condenser
  3. temperatureDuring the course of heating
  4. temperatureAfter 37 hours of heating
  5. temperatureto cool to ambient temperature
  6. concentrationThe mixture was concentrated under reduced pressure
  7. custompartitioned between ethyl acetate (60 mL) and water (30 mL)
  8. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  9. washThe combined organic layers were washed with saturated aqueous NaCl (10 mL)
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude material was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f6faf946cebe42d590890c180e3ed5c0
Source dataset
uspto-grants-2015_10
Patent number
US09163027B2

Reaction notes

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