Imine and Ugi synthesis


The library of 218 potential enoyl reductase inhibitors provided by Find-A-Drug consists of diketopiperazine derivatives. The four-component Ugi reaction followed by a cyclization should prove to be a convenient and general approach to making these compounds. Many of these reactions require DOPAL as the aldehyde component. Before attempting the Ugi reaction with DOPAL, we are practicing with other commercially available aldehydes. In the more recent experiments, detailed analysis of the progress of the reactions using NMR with JSpecView permits the determination of the rate constants of imine formation.

More on the Ugi reaction from our Reference page.

Experiments in progress or with pending issues are marked by *

Imine Analysis

Attempts with DOPAL:
EXP023 - Khalid

Our most recent attempts
Exp110 Reaction of the Ugi product 108C with 50% TFA in CDCl3 (prolonged exposure) - Khalid / Jessica
Exp109 Ugi synthesis using 5-(Trifluoromethyl)-2-furylmethylamine, benzaldehyde, benzylisocyanide and boc-glycine - Khalid
Exp108 Ugi synthesis using furfurylamine, benzaldehyde, benzylisocyanide and boc-glycine - Khalid
Exp107 Tert-butylation of furfurylamine with t-butanol and Amberlyst 15(H) in CDCl3 at room temperature - Khalid
Exp105 FriedelCrafts tert-butylation of N-(2-furylmethyl)acetamide-Khalid
Exp104 Ugi synthesis using furfurylamine, veratraldehyde, tert-butylisocyanide and boc-glycine - Khalid
Exp103 Synthesis of the acetamide of furfurylamine -Khalid
Exp102 FriedelCrafts tert-butylation of N-(2-furylmethyl)acetamide-Khalid
Exp101 Reaction of the Ugi product 99C with 50% TFA in CDCl3 (prolonged exposure) - Khalid
Exp100 Ugi synthesis using tert-butylamine, benzaldehyde, tert-butylisocyanide and boc-glycine - Khalid
Exp099 Ugi synthesis using furfurylamine, benzaldehyde, tert-butylisocyanide and boc-glycine - Khalid
Exp098 Reaction of the Ugi product 64C with 50% TFA in CDCl3 (prolonged exposure) - Khalid
Exp097 Reaction of the Ugi product 86B with 50% TFA in CDCl3 (prolonged exposure) - Khalid
Exp096 Ugi synthesis using furfurylamine, veratraldehyde, tert-butylisocyanide and boc-glycine - Khalid
Exp095 Ugi synthesis using furfurylamine, veratraldehyde, tert-butylisocyanide and boc-glycine - Khalid
Exp094 3,4-Dihydroxybenzaldehyde, 5-methylfurfurylamine, Boc-Glycine, t-Butyl isocyanide (CHCl3 for imine, MeOH for rxn) - Sean
Exp093 Ugi synthesis using aniline, benzophenone, tert-butylisocyanide and boc-glycine - Khalid
Exp092 Test for the stability of the furan ring of amide of BocGlycine and 5MFA in 50% TFA - Khalid
Exp091 Reaction of the Ugi product 62E with 50% TFA in CDCl3.Khalid
Exp089 Ugi synthesis using tert-butylamine, benzaldehyde, tert-butylisocyanide and boc-glycine - Khalid
Exp088 Synthesis of an amide of Boc Glycine and 5-methylfurfurylamine in methanol-d4- Khalid
*Exp087 Synthesis of the Boc-deprotected amine of the Ugi product 86C- Khalid
Exp086 Benzaldehyde, 5-methylfurfurylamine, tert-butylisocyanide, Boc-glycine - Khalid
Exp085Crotonaldehyde, Methylfurfurylamine in CDCl3 - jgiammarco
Exp084Piperonal, Aniline, Boc-Gly-OH, Tertbutyalisocyanide in CDCl3- jgiammarco
Exp083Crotonaldehyde, Tertbutyalamine, Boc-Gly-OH, Tertbutylisocyanide in CDCl3- jgiammarco
Exp082 Synthesis of the Boc-deprotected amine of the Ugi product(64C-2) - Khalid
Exp081 Test for the stability of the furan ring of N-[(5-methyl-2-furyl)methyl]acetamide in 10% TFA - Khalid
Exp080 Piperonal, tertbutylamine, Boc-Gly-OH, tertbutylisocyanide (CDCl3) -jgiammarco
Exp078 Synthesis of the acetamide of 5-methyl furfurylamine -Khalid
Exp077 Piperonal, tertbutylamine, Boc-Gly-OH(CDCl3) -jgiammarco
Exp076 Piperonal, tertbutylamine, Boc-Gly-OH (MeOH) -jgiammarco
Exp073 Test for the stability of the furan ring of 5-Methylfurfurylamine in TFA - Khalid
Exp070 Ugi Product (diamide) Cycliztion using 50% TFA in CDCl3 - Khalid
*Exp069 Piperonal, tertbutylamine, Boc-Gly-OH, tertbutyl isocyanide in MeOH-d4 - jgiammarco
Exp068 Reaction of Boc-Glycine with 10%TFA in CDCl3 - Khalid
Exp067 Ugi Product (diamide) Cycliztion using 10% TFA in CDCl3 - Khalid
Exp066 Piperonal, tertbutylamine, Boc-Gly-OH, tertbutyl isocyanide in MeOH-d4 - jgiammarco
*Exp065 Ugi Product (diamide) Cycliztion using 10% TFA in CDCl3 - Alicia
*Exp064 [Veratraldehyde, 5-Methyl furfurylamine], Benzyl Isocyanide, Boc-Gly-OH in MeOH - Khalid
*Exp063 3,4-dihydroxybenzaldehyde, 5-methylfurfurylamine, Boc-Gly-OH, benzyl isocyanide - Sean
*Exp062 Piperonal, 5-methylfurfurylamine, Boc-Gly-OH, tertbutyl isocyanide in MeOH - Alicia
*Exp061 3,4-dihydroxybenzaldehyde, 5-methylfurfurylamine, Boc-Gly-OH, benzyl isocyanide - Sean
*Exp060 [Veratraldehyde, 5-Methyl furfurylamine], Benzyl Isocyanide, Boc-Gly-OH in MeOH- Khalid
*Exp059 Piperonal, 5-methylfurfurylamine, Boc-Gly-OH, tertbutyl isocyanide in MeOH - Alicia
*Exp058 Piperonal, tertbutylamine, Boc-Gly-OH, tertbutyl isocyanide in MeOH-d4 - jgiammarco
Exp057 (3,4-dihydroxybenzaldehyde, 5-methylfurfurylamine in MeOH-d4) - Sean
Exp056 Boc-Met-OH and 5-Methyl furfurylamine in MeOH-d4 - Khalid
Exp055 Boc-Gly-OH and 5-Methyl furfurylamine in MeOH-d4 - Khalid
Exp054 [Veratraldehyde, 5-Methyl furfurylamine], Benzyl Isocyanide and final addition of Boc-Gly-OH in MeOH-d4 - Khalid
Exp053 Boc-Gly-OH and tert-butyl isocyanide in MeOH-d4 - Khalid
*Exp052 Piperonal, 5-methylfurfurylamine, BocGly-OH, tert-butyl isocyanide in MeOH - Alicia
Exp051 Piperonal and tert-butylamine, Boc-Gly-OH and dehydration with MgSO4 in MeOH-d4 - jgiammarco
Exp050 Boc-Gly-OH and Benzyl isocyanide in MeOH-d4 - Khalid
Exp049 Boc-Gly-OH and 2-morpholinoethyl isocyanide in MeOH-d4 - Khalid
*Exp048 (piperonal, tertbutylamine, Boc-Gly-OH, 2-morpholino ethylisocyanide in MeOH-d4) - jgiammarco
Exp047 (3,4-dihydroxybenzaldehyde, 5-methylfurfurylamine in MeOH-d4) - Sean
Exp046 (3,4-dimethoxybenzaldehyde, 5-methylfurfurylamine, BocGly, 2-morpholinoethylisocyanide in MeOH-d4) - Khalid
*Exp045 (3,4-dimethoxybenzaldehyde, 5-methylfurfurylamine, BocGly, 2-morpholinoethylisocyanide in CDCl3) - Khalid
Exp044 Formation of the imine of Phenyl acetaldehyde and tert-butylamine in CDCl3- Khalid
Exp043 Formation of the imine of Piperonal and 5-Methyl furfurylamine in MeOH-d4 - Alicia
Exp042 Formation of the imine of Phenyl acetaldehyde and tert-butylamine in CDCl3- Khalid / Lin
Exp041 Formation of the imine of Piperonal and 5-Methyl furfurylamine in MeOH-d4- Alicia
Exp040 Formation of the imine of Piperonal and 5-Methyl furfurylamine in CDCl3- Alicia
Exp038 (Phenylacetaldehyde, 5-methylfurfurylamine, BocGly, 2-morpholinoethylisocyanide in CDCl3 ) - Alicia
Exp034 (Phenylacetaldehyde, 5-methylfurfurylamine, BocGly, 2-morpholinoethylisocyanide in CDCl3) - Alicia
Exp032 (Imine mix from Exp036, Boc-Met-OH, 2-morpholinoethylisocyanide in MeOH ) - Khalid
Exp031 (Phenylacetaldehyde after distillation, -methylfurfurylamine, BocGly-OH, benzylisocyanide in MeOH ) - Jgiammarco
Exp030 (Piperonal, tertbutylamine, Boc-Gly-OH, 2-morpholino ethylisocyanide in MeOH) - Khalid
Exp029 (Piperonal, 5-methylfurfurylamine, BocGly-OH, benzylisocyanide in MeOH then CDCl3) - Alicia
Exp028 (Formaldehyde, tertbutylamine, Boc-Gly-OH, 2-morpholino ethylisocyanide in 1M LiCl/Water) - Khalid
Exp027 (Formaldehyde, tertbutylamine, Boc-Gly-OH, 2-morpholino ethylisocyanide in Methanol) - Khalid
Exp026 (Piperonal, 5-methylfurfurylamine, BocGly-OH, benzylisocyanide in MeOH ) Lin
EXP022 (3,4-dimethoxybenzaldehyde, 5-methylfurfurylamine, BocGly-OH, benzylisocyanide in MeOH ) Khalid
EXP021 (3,4-dihydroxybenzaldehyde, 5-methylfurfurylamine, BocGly-OH, benzylisocyanide in MeOH ) jgiammarco
EXP020 (3,4-dihydroxybenzaldehyde, 5-methylfurfurylamine, BocGly-OH, benzylisocyanide in MeOH ) jgiammarco
EXP019 (Piperonal, 5-methylfurfurylamine, BocGly-OH, benzylisocyanide in MeOH) - Lin
EXP018 (3,4-dihydroxybenzaldehyde, 5-methylfurfurylamine, BocGly-OH, benzylisocyanide in MeOH) jgiammarco
EXP017 (Piperonal, 5-methylfurfurylamine, BocMet-OH, benzylisocyanide in MeOH) - Lin
EXP014 (Phenylacetaldehyde, 5-methylfurfurylamine, BocMet-OH, benzylisocyanide in MeOH) - Khalid
EXP006 (Phenylacetaldehyde, 5-methylfurfurylamine, Boc-Met-OH, benzylisocyanide in MeOH) - Khalid
EXP003 (Phehylacetaldehyde, 5-methylfurfurylamine, Boc-Met-OH, benzylisocyanide in MeOH) - Brett/Alicia/jgiammarco