exp160b.gif

Objective

To synthesize a Ugi adduct from furfurylamine, phenanthrene-9-carboxaldehyde, 3,4-dihydroxyphenyl acetic acid and n-butyl isocyanide in methanol using Ugi 4CR following Explan005. The target compound was ranked 19 in the DEXP014-V1B file from D-EXP014. The purpose of this experiment is to synthesize an anti-malarial compound based on the inhibition of falcipain-2, as described in this summary post.

Procedure

To a one dram vial, charged with methanol (1mL) and furfurylamine, phenanthrene-9-carboxaldehyde, 3,4-dihydroxyphenyl acetic acid and n-butyl isocyanide (0.5mmol each) was added in that order. After each addition, the resulting solution was vortexed for at least 15 seconds and confirmed that a homogeneous solution had been obtained. The vial was capped tight and left at room temperature for 1 day.

ID/ Lib Rank
Solvent
Aldehyde
Amine
Carboxylic Acid
Isocyanide
Ppt Yes/No
160/19
Methanol
Phenanthrene-9-
carboxaldehyde
furfurylamine
3,4-dihydroxyphenyl
acetic acid
n-butyl isocyanide
No
Quantity
1000uL
0.5 mmol, 103.12 mg
0.5mmol, 44.19uL
(density=1.099g/ml)
0.5mmol, 84.08 mg
0.5mmol, 52.28 ul
(density=0.795g/ml)


Density information: Ugi Chemicals

Results


5 min after mixing
all components (160A)

One day after mixing
all components (160B)

Exp160day1.JPG
Exp160day2.JPG

After sonication (160C)

Exp160day2a.JPG



Discussion


The phenanthrene-9-carboxaldehyde appeared to be less soluble than the other starting materials. The vortex time recorded in the log is five minutes compared to the 15 seconds necessary for the other components.
All results are recorded Master Table and Workflow Tables.


Conclusion


After the vial set out at room temperature for a day and was sonicated. No precipitate was formed.


Log

2008-01-18
17:13- Started to weigh out the phenanthrene-9-carboxaldehyde.
17:20- Started to weigh out the 3,4-dihydroxyphenyl acetic acid.
17:25- Charged a vial with 1 mL of methanol.
17:28- Added the furfurylamine to the vial and vortexed for 15 seconds. A clear solution was obtained.
17:33- Added the phenanthrene-9-carboxaldehyde to the vial and vortexed for 5 minutes until a clear solution was obtained.
17:38- Added the 3,4-dihydroxyphenyl acetic acid to the vial and vortexed for 15 seconds. A clear solution was obtained.
17:44- Added the n-butyl isocyanide to the vial and vortexed for 15 seconds. A clear solution was obtained.
17:49- Took a photo (160A) of the vial, and left it to sit for 24 hours at room temperature.

2008-01-19
16:50- Took a photo (160B) of the vial. There was no precipitate that formed.
16:55- Put the vial into the sonicator for ten minutes.
17:05- Removed the vial and took another picture (160C). No solid has formed.

Tags


furfurylamine InChI=1/C5H7NO/c6-4-5-2-1-3-7-5/h1-3H,4,6H2InChIKey:DDRPCXLAQZKBJP-UHFFFAOYAX
phenanthrene-9-carboxaldehyde InChI=1/C15H10O/c16-10-12-9-11-5-1-2-6-13(11)15-8-4-3-7-14(12)15/h1-10H InChIKey: QECIGCMPORCORE-UHFFFAOYAE
3,4-dihydroxyphenyl acetic acid InChI=1/C8H8O4/c9-6-2-1-5(3-7(6)10)4-8(11)12/h1-3,9-10H,4H2,(H,11,12) InChIKey: CFFZDZCDUFSOFZ-UHFFFAOYAU
n-butyl isocyanide InChI=1/C5H9N/c1-3-4-5-6-2/h3-5H2,1H3 InChIKey: FSBLVBBRXSCOKU-UHFFFAOYAR
Ugi product InChIKey: NVRQEIRPSKDYGZ-UHFFFAOYAO