exp170a.gif

Objective

To synthesize a Ugi adduct from furfurylamine, phenanthrene-9-carboxaldehyde, phenyl acetic acid and n-butyl isocyanide in methanol using Ugi 4CR following Explan005. The target compound was ranked 29 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, phenyl 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
170/29
Methanol
Phenanthrene-9-
carboxaldehyde
furfurylamine
phenyl acetic acid
n-butyl isocyanide
Aborted
Quantity
1000uL
0.5 mmol, 103.1 mg
0.5mmol, 44.2uL
(density=1.022g/ml)
0.5mmol, 68.08 mg
0.5mmol, 52.28 ul
(density=0.795g/ml)

Density information: Ugi Chemicals


Results

(170A)
(170B)
Exp170A.JPG
Exp170B.JPG
(170C)

Exp170C.JPG




Discussion

All results are recorded Master Table and Workflow Tables.

Conclusion

A solid was formed but it was not washed - experiment aborted. Next time centrifugation and only vortexing should be used (no sonication), as described in EXPLAN005.

Log

2008-02-07

16:07- Charged a vial with 1 ml of methanol.
16:10- Started to weigh out the phenanthrene-9-carboxaldehyde
16:15- Started to weigh out the phenylacetic acid.
16:19- Added the furfurylamine to the vial and vortexed for 15 seconds. A clear solution was obtained.
16:21- Added the phenanthrene-9-carboxaldehyde to the vial and vortexed for 5 minutes. No clear solution was obtained.
16:28- Added the phenylacetic acid and vortexed for 3 minutes. A clear solution was obtained.
16:32- Added the n-butylisocyanide and vortexed for 15 seconds. A clear solution was obtained.
16:35- Took a photo of the vial (170A).

2008-02-08

15:15- Took another photo (170B) of the solid Ugi product in the vial.
16:14- Vortexed the product in the vial for 15 seconds. No solvent could be seen. this is where you should have centrifuged the first time
16:16- Added 500 ul of methanol to the vial and vortexed for 15 seconds. The solvent remained on top of the solid.
16:18- Sonicated the vial containing undissolved solid and methanol on top for 1 min, then vortexed it for 15 sec. At this time the solid packing at the bottom of the vial mixed well with the solvent and a pasty mixture covered the walls of the vial.
16:21- The vial was then emptied onto a clean watch glass.
16:22- Next 250 ul of methanol was added to the vial vortexed. Then the remaining solid was emptied onto the watch glass.
16:25- A photo was taken (170C) of the watch glass and empty vial. The methanol will evaporate so the product can be weighed.


Tags


furfurylamine InChI=1/C5H7NO/c6-4-5-2-1-3-7-5/h1-3H,4,6H2 InChIKey: 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
phenyl acetic acid InChI=1/C8H8O2/c9-8(10)6-7-4-2-1-3-5-7/h1-5H,6H2,(H,9,10) InChIKey: WLJVXDMOQOGPHL-UHFFFAOYAR
n-butyl isocyanide InChI=1/C5H9N/c1-3-4-5-6-2/h3-5H2,1H3 InChIKey: FSBLVBBRXSCOKU-UHFFFAOYAR
Ugi Product (not found in CS) InChI=1/C3 ​3H32N2O3/c​1-2-3-19-3​4-33(37)32​(30-22-25-​14-7-8-16-​27(25)28-1​ 7-9-10-18-​29(28)30)3​5(23-26-15​-11-20-38-​26)31(36)2​1-24-12-5-​ 4-6-13-24/​h4-18,20,2​2,32H,2-3,​19,21,23H2​,1H3,(H,34​,37) InChIKey: RGGYLRDGJAJICY-UHFFFAOYAH