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TCI Practical Example: Di-Cbz Guanidinylation of Amine Using the Pyrazole Derivative

We are proud to present the di-Cbz guanidinylation of 4-bromophenethylamine using 1-[N,N'-(di-Cbz)amidino]pyrazole.

Used Chemicals

• 4-Bromophenethylamine [B3454]
• 1-[N,N'-(Di-Cbz)amidino]pyrazole [B3605]
• THF

Procedure

A solution of 4-bromophenethylamine (200 mg, 1.00 mmol) and 1-[N,N'-(di-Cbz)amidino]pyrazole (416 mg, 1.10 mmol) in THF (1.7 mL) was stirred at ambient temperature for one day. The reaction mixture was concentrated, and the residue was purified by column chromatography (ethyl acetate:hexane = 0:100 – 10:90 on silica gel) to give the guanidinylated compound 1 as a pale yellow oil (435 mg, 85% yield).

Experimenter's Comments

The reaction mixture was monitored by TLC (ethyl acetate:hexane = 1:3, Rf = 0.45).

Analytical Data

Guanidinylated Compound 1

¹H NMR (270 MHz, DMSO-d₆); δ 11.58 (s, 1H), 8.44 (t, J = 6.4 Hz, 1H), 7.49–7.31 (m, 12H), 7.18 (d, J = 8.1 Hz, 2H), 5.20 (s, 2H), 5.04 (s, 2H), 3.55 (brq, J = 6.4 Hz, 2H), 2.80 (t, J = 6.4 Hz, 2H)

Lead Reference

• Urethane protected derivatives of 1-guanylpyrazole for the mild and efficient preparation of guanidines
  • M. S. Bernatowicz, Y. Wu, G. R. Matsueda, Tetrahedron Lett. 1993, 34, 3389.