Di-tert-butyl Iminodicarboxylate → {4-[3,5-Bis-({4-[tert-butoxycarbonyl-(4-tert-butoxycarbonylamino-butyl)-amino]butylamino}-methyl)-benzylamino]-butyl}-(4-tert-butoxycarbonylamino-butyl)-carbamic acid tert-butyl ester

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Reaction Steps

1,3,5-Triformyl benzene 16 (32 mg, 0.197 mmol) was dissolved in 25% MeOH/CH2Cl2 (5 mL). A solution of Boc-protected homospermidine 12 (265 mg, 0.738 mmol) was added via an addition funnel. The reaction mixture was stirred overnight under a N2 atmosphere. Loss of starting material was monitored via 1H NMR and the disappearance of the aldehyde proton at 10.21 ppm. Upon conversion of the starting material, the solvent was removed in vacuo and the crude material was redissolved in a solution of 50% MeOH/CH2Cl2. To this new solution was added NaBH4 (83 mg, 2.19 mmol) at 0° C. The solution was stirred overnight under a N2 atmosphere. The solvents were removed under reduced pressure. The aqueous layer was extracted 3 times in CH2Cl2 and saturated Na2CO3. The organic layers were combined and dried over anhydrous Na2SO4, filtered, and concentrated. Crude material was dissolved in dry THF (10 mL) and allowed to stir for 20 minutes at 0° C. Solid 2-(tert-butoxycarbonyloyimino)-2-phenylacetonitrile (Boc-On, 51 mg, 0.206 mmol) was added to change the Rf value of the starting diBoc amine and the solution was allowed to stir for 2 hours at 0° C. Upon completion the solvents were removed under reduced pressure. Residue was redissolved in CH2Cl2 and the aqueous layer was extracted 3 times in CH2Cl2 and saturated Na2CO3. The organic layers were separated, dried over anhydrous Na2SO4, filtered, and concentrated. Flash column chromatography (92% CH2Cl2, 7% MeOH, 1% NH4OH Rf=0.40) afforded 17 (94 mg, 0.079 mmol, 40%). 1H NMR (CDCl3): δ 7.16 (s, 3H), 4.72 (s, 3H), 3.78 (s, 6H), 3.18 (m, 18H), 2.64 (t, 6H), 1.69-1.19 (m, 78H).

Provenance & Evidence