Objective

To synthesize a Ugi adduct (wrong link) from benzaldehyde, 5-methyl-2-furylmethylamine, 3-(4-methoxyphenyl)propionic acid, and tert-Butyl isocyanide in methanol using Ugi 4CR following Explan005. The target compound was ranked 159 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 (1 ml), 5-methyl-2-furylmethylamine, benzaldehyde, 3-(4-methoxyphenyl)propionic acid and tert-butyl isocyanide. (0.5mmol each) was added in that order. After each addition, the resulting solution was vortexed for 15 seconds and confirmed that a homogeneous solution had been obtained. The vial was capped tight and left at room temperature.



ID/ Lib Rank
Solvent
Aldehyde
Amine
Carboxylic Acid
Isocyanide
Ppt Yes/No
155/159
Methanol
benzaldehyde
5-methyl-2-furylmethylamine
3-(4-methoxyphenyl)propionic acid
tert-butylisocyanide
No
Quantity
1000uL
0.5mmol, 50.78ul
(density=1.045 g/ml)
0.5mmol, 55.9ul
(density=0.997g/ml)
0.5mmol, 90.2mg
0.5mmol, 56.6uL
(density=0.735g/ml)

The densities were obtained the the Sigma-Aldrich website (www.sigmaaldrich.com)


Results

5 min after mixing
all components (155A)


Approx. 24 hours after
mixing all components (155B)

Exp155day1.JPG

Exp155day2.JPG


After sonication

Exp155day2a.JPG




Discussion


All results are recorded in the Master Table of all Ugi synthesis attempts

Conclusion


After the vial set out at room temperature for a day and was sonicated, no Ugi product was formed.

Log


2008-01-10
15:18- Charged vial with 1ml of methanol
15:23- Weighed out the acid.
15:26- Added amine to vial and vortexed for 15 seconds. A clear solution was achieved.
15:28- Added the aldehyde to the vial and vortexed for 15 seconds. A clear solution was achieved.
15:30- Added acid to the solution and vortexed for 15 seconds and the acid was dissolved. A clear solution was achieved.
15:32- Added isocyanide to the vial and vortexed for 15 seconds. A clear solution was achieved.
15:34- The vial was left to sit at room temperature for a day. The liquid is an amber/brown color.
15:39- Took picture of the vial.

2008-01-11
15:25- Took picture of the vial. No precipitate has formed yet.
15:38- Put the vial into the sonicator for ten minutes.
15:48- Removed the vial from the sonicator. No precipitate has formed.
15:58- Took another picture of the vial after sonication.

Tags


Benzaldehyde InChI=1/C7H6O/c8-6-7-4-2-1-3-5-7/h1-6H InChIKey: HUMNYLRZRPPJDN-UHFFFAOYAE
5-methyl-2-furylmethylamine InChI=1/C6H9NO/c1-5-2-3-6(4-7)8-5/h2-3H,4,7H2,1H3 InChIKey: YSEAGSCGERFGBL-UHFFFAOYAH
3-(4-methoxyphenyl)propionic acid InChI=1/C10H12O3/c1-13-9-5-2-8(3-6-9)4-7-10(11)12/h2-3,5-6H,4,7H2,1H3,(H,11,12) InChIKey: FIUFLISGGHNPSM-UHFFFAOYAL
tert-Butyl isocyanide InChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3 InChIKey: FAGLEPBREOXSAC-UHFFFAOYAL