EXP026

==

=Objective= To produce a [|diketopiperazine] by a Ugi synthesis and cyclization using [|piperonal], [|5-methylfurfurylamine], [|Boc-Gly-OH], and [|benzylisocyanide] using the protocol described [|here] with the modification that THF will be used instead of 1,2-dichloroethane in the cyclization step. This compound is not an anti-malarial target but is a close analog of the product that we wish to make once the [|catechol aldehyde] is obtained.

=Procedure= Methanol (20 mL), [|piperonal] (73.75mg, 0.49 mmol), [|Boc-Gly-OH] (85.85 mg, 0.49 mmol), [|5-methylfurfurylamine] (55µL, 0.49 mmol), and [|benzylisocyanide] (60µL, 0.43 mmol) were added to a 50 mL Erlenmeyer flask. The flask was stoppered and the mixture was stirred for 24 hr, then evaporated on rotovap and high vacuum.

=Results=

Characterization of 26A
-- [|Picture of setup] with a colorless solution, right after stirring was started. -- TLC of 26A against piperonal and benzylisocyanide in 1:1 methylene chloride to hexanes. Left to right: piperonal, benzylisocyanide, and 26A ([|Picture under UV light]).

Characterization of 26B
-- [|H-NMR], [|C13-NMR] -- TLCs of 26B in [|pure methylene chloride] and [|2% methanol].

Characterization of 26B-F1
-- [|H-NMR], [|C13-NMR], [|C13-NMR 30s relaxation] -- [|MALDI] (not enough sample?) -- mass: 131.9 mg

=Discussion= -- HNMRs of starting materials: [|piperonal], [|Boc-Gly-OH], [|5-methylfurfurylamine] and [|benzylisocyanide]. -- C13-NMRs of startinng materials: [|piperonal], [|Boc-Gly-OH], 5-methylfurfurylamine (//**pending**//) and [|benzylisocyanide].

The CMRs of 26B and 26B-F1 are almost identical. The peak at 190 ppm in 26B was suspected to be a glitch, which is confirmed by its absence in 26B-F1. The strong peak at 175 ppm in both CMRs of 26B-F1 is not present in 26B. If it were a glitch it would not be expected to show up in both spectra.

=Conclusion=

=Log=

2006-08-30
1. **14:53)** Mixed chemicals and started stirring at room temperature, stir setting 3. The solution was colorless. The 5-methylfurfurylamine and the benzylisocyanide were added by using a 500 microliter GC syringe.

2006-08-31
2. **14:53)** Stopped stirring the solution, which is now a yellow color. 3. **14:58)** Rotovap solution at 60C. 4. **16:10**) Sample was taken off rotovap. 5. **16:24)** Sample was put on high vacuum at 1.1 mmHg for 10 hours to get 26A. Mass of 26A is 254.4 mg.

2006-09-01
6. Ran TLC of 26A against piperonal and benzylisocyanide in 1:1 methylene chloride to hexanes. 7. 5 mL of methanol was added to the sample (26A).

2006-09-27
8. **15:01)** Evaporated the methanol by nitrogen for 2 hours. 9. **17:10)** Put solution on high vac for 1.5 hour to get 26B 191.1 mg.

2006-10-04
10. Ran TLC of 26B against piperonal and benzylisocyanide in 3:1 methylene chloride to hexanes ([|Picture]). 11. Ran TLC of 26B in pure methylene chloride ([|Picture]).

2006-10-04
12. Ran TLC of 26B in [|2% methanol] and [|4% methanol].

2006-10-10
13. Flash chromatography (28.5g silica) was done on 26B with methylene chloride then 2% methanol in methylene chloride and one fraction 26B-F1 was collected. 14. 26B-F1 was rotovaped for 45 minutes.

2006-10-11
15. **14:30)** 26B-F1 was put on high vac for 45 minutes. The mass of the crude product was 131.9 mg. =Tags= [|Benzylisocyanide] [|InChI=1/C8H7N/c1-9-7-8-5-3-2-4-6-8/h2-6H,7H2] [|Piperonal][|InChI=1/C8H6O3/c9-4-6-1-2-7-8(3-6)11-5-10-7/h1-4H,5H2] [|Boc-Gly-OH][|InChI=1/C7H13NO4/c1-7(2,3)12-6(11)8-4-5(9)10/h4H2,1-3H3,(H,8,11)(H,9,10)] [|5-methylfurfurylamine][|InChI=1/C6H9NO/c1-5-2-3-6(4-7)8-5/h2-3H,4,7H2,1H3] ugi019:[|InChI=1/C29H33N3O7/c1-19-10-12-22(38-19)17-32(25(33)16-31-28(35)39-29(2,3)4)26(21-11-13-23-24(14-21)37-18-36-23)27(34)30-15-20-8-6-5-7-9-20/h5-14,26H,15-18H2,1-4H3,(H,30,34)(H,31,35)] [|DKP019][|InChI=1/C17H16N2O5/c1-10-2-4-12(24-10)8-19-15(20)7-18-17(21)16(19)11-3-5-13-14(6-11)23-9-22-13/h2-6,16H,7-9H2,1H3,(H,18,21)]

media type="custom" key="6657"