Mannich reactions of a resin-bound terminal alkyne

Tetrahedron Letters

Volumn 38, Issue 36, 1997, Pages 6347-6350

  Youngman, Mark A ^a   Dax, Scott L ^a  

^a R W JOHNSON PHARMACEUTICAL RES I   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PIPERAZINE DERIVATIVE; PIPERIDINE DERIVATIVE; PYRROLIDINE DERIVATIVE;

ARTICLE; CATALYSIS; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IN VITRO STUDY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS; TECHNIQUE;

EID: 0030765701     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)01460-3     Document Type: Article

References (12)

1. (a) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron 1996, 52, 4527-4554.
2. (b) Balkenhohl, F.; von dem Bussche-Hunnefeld, C.; Lansky, A.; Zechel, C. Angew. Chem. Int. Ed. Engl. 1996, 35, 2288-2337.
3. Zhang, H.-C.; Brumfield, K., Maryanoff, B. E. Tetrahedron Lett. 1997, 38, 2439-2442.
4. Young, J. K.; Nelson, J. C.; Moore, J. S. J. Am. Chem. Soc. 1994, 116, 10841-10843.
5. Pavia, M. R.; Whitesides, G. M.; Hangauer, D. G.; Hediger, M. E. Patent WO 95/04277,1995.
6. Pei, Y.; Moos, W. H. Tetrahedron Lett. 1994, 35, 5825-5828.
7. Tramontini, M.; Angiolini, L. Mannich Bases: Chemistry and Uses, CRC Press Ine, Boca Raton, FL 1994.
8. Kobayashi, S.; Moriwaki, M.; Akiyama, R.; Suzuki, S.; Hachiya, I. Tetrahedron Lett. 1996, 37, 7783-7786.
9. Cook, S. C.; Dax, S. L. Biooorg. & Med. Chem. Lett. 1996, 6, 797-802.
10. Into a dry 500 ml round-bottom flask was placed 2-chlorotrityl chloride resin (14.35 g, 1.04 mmol/g, 14.9 mmol, 1 equiv.), DMF (200 ml) and a stir bar. Propargyl amine (20.0 ml, 292 mmol, approx. 20 equiv.) was added via syringe and the mixture was gently stirred for 16 hrs. The reaction was filtered through a fritted glass funnel and the resultant resin was washed: DMF (4 x 300mL), THF (3 x 300mL) and DCM (4 x 300mL). The resin was dried in vacuo and used in the subsequent steps. A small portion of the resin was cleaved with 25% TFA/DCM (v/v) and the solvents were removed in vacuo to give a white powder; NMR of this material was indistinguishable from authentic propargyl amine TFA salt.
11. 4OH, 3 x 10mL DMF and 4 x 10mL DCM.
12. 3OD for fixed frequency lock and chemical shift; HPLC were obtained on a Hewlett Packard HP1050 using a gradient (10:90 to 90:10) of acetonitrile/water with 0.1% trifluoroacetic acid as eluent and UV detection at either 217 nM or 220 nM; Mass spectra were obtained on a Micromass Platform II using electospray ionization and probe = 4.0 kV or on a Hewlett Packard HP5989 MS Engine using particle beam chemical ionization with ammonia as reagent gas.