Objective

To synthesize one Ugi product following the EXPLAN005 . The compound will contribute towards a library for falcipain-2 inhibitors. This compounds was ranked 12 in the DEXP014-V2B file from D-EXP014.

Procedure

As described in Explan005
One Ugi reaction was carried out in a vial labeled Exp153-1.To one dram vial was added methanol (500 ul), phenanthrene-9-carboxaldehyde (0.5mmol, 503.1mg), methylamine(in 2M methanolic solution, yielding 250 ul for 0.5mmol), 1-pyrenebutyric acid (0.5mmol, 144.1mg), another 500 ul of methanol, and t-butyl isocyanide (0.5mmol, 56.5ul), in that order. After each addition, the solution was vortexed for 15 seconds. The vial was also sonicated for one hour immediately after the addition of all components.The formation or absence of precipitate was noted. The dram vials were left at room temperature.

Comp ID/ Lib Rank
Solvent
Aldehyde
Amine
Carboxylic Acid
Isocyanide
Ppt Yes/No
153-1/12
Methanol (1000uL)
Phenanthrene-9-carboxaldehyde (0.5 mmol, 103.1 mg)
Methylamine (250uL,0.5mmol, 2M methanolic solution)
1-pyrenebutyric acid (0.5mmol, 144.1 mg)
t-butyl isocyanide (0.5mmol, 56.6ul)
reactant insolubility problem

Results

All results are recorded in the Master Table of all Ugi Synthesis Attempts

Photo of 153-1-A taken at 16:14 immediately after adding all components (before sonification):
exp_153_photo_before.jpg

Discussion

Speculate about what might be causing lack of solubility - is your experience consistent with what others in our group have observed?

The lack of solubility may arise from the fact that the amount of methanol in the normal procedure was insufficient to dissolve the compounds. Also, the compound was noted as insoluble upon the addition of 1-pyrenebutyric acid. Various factors may exist that could have caused this insolubility, including contamination of the aldehyde, amine, or acid. The acid utilized, 1-pyrenebutyric acid, was also used before Exp 153, in Exp 147, and the sample went into solution immediately following the the appropriate vortexing. At this point, an alternate cause of this insolubility in Exp 153 may also stem from the components not being able to solubilize with each other if contamination is negative.

But which compound specifically are you saying is insoluble? And if you are saying that a component is insoluble at this concentration, is that what all the other experiments report?

Conclusion

Experiment aborted

Log

11/28/2007

Exp 153-1

15:30 Weighed out phenanthrene 9-carboxaldehyde and 1-pyrenebutyric acid weighing paper
15:40: Added methanol (500uL) into the dram vials, followed by 15 seconds vortexing.
15:52: Added aldehyde into the dram vials, followed by 15 seconds vortexing.
15:57: Added amine into the dram vials, followed by 15 seconds vortexing.
16:00: Added acid into the dram vials followed by 15 seconds vortexing
16:05: Noticed poor solubility and added another 500 ul of methanol to vial, followed by 15 seconds of vortexing
16:10: Added isocyanide into dram vials followed by 15 seconds vortexing
16:14: Took picture of vial (153-1-A) before placing into sonicator
16:15: Placed vial in sonicater for one hour.
17:15: After one hour of sonification, solution still remained inhomogenous.

Tags

tert-butylisocyanide InChI=1/C5H9N/c1-5%282,3%296-4/h1-3H3
Phenanthrene 9-carboxaldehyde InChI=1/C15H10O/c16-10-12-9-11-5-1-2-6-13%2811%2915-8-4-3-7-14%2812%2915/h1-10H
Methylamine InChI=1/CH5N/c1-2/h2H2,1H3
1-pyrenebutyric acid InChI=1/C20H16O2/c21-18%2822%296-2-3-13-7-8-16-10-9-14-4-1-5-15-11-12-17%2813%2920%2816%2919%2814%2915/h1,4-5,7-12H,2-3,6H2,%28H,21,22%29/f/h21H