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Molecules2001, 6, M197

1-(2-Ethylmorpholino)-5-benzyloxy-3-(1-napthoyl)pyrrolopyridine

Gerard P. Moloney

Department of Medicinal Chemistry, Victorian College of Pharmacy (Monash University), 381 Royal Parade Parkville, Victoria 3052, Australia, E-mail: [email protected]

Received: 4 September 2000 / Accepted: 29 September 2000 / Published: 25 March 2001

As part of a research programme targeting novel indole-like molecules as potential cannabinoid agonists [1-4] we synthesised N-(2-ethylmorpholino)-3-bis keto(1-naphthyl) oxindole.

To a stirred suspension of 1-[4-(2-ethylmorpholine)]-5-benzyloxypyrridoindole (32.5 mg, 0.0964 mmol) in anhydrous dichloromethane (3.0 mL) under an atmosphere of nitrogen was added 1-naphthoyl chloride (23.0 mg, 0.19 mmol). The reaction mixture was stirred at room temperature and aluminium chloride (26.2 mg, 4.67 mmol) was added portionwise. The reaction mixture was stirred for 105 minutes. Water was added and the aqueous phase was extracted with dichloromethane, dried over magnesium sulphate, filtered, and evaporated under reduced pressure to afford a yellow/orange oil which was purified by column chromatography eluting with chloroform/methanol (99/1) to afford (284.1 mg, 60.0 %) of the desired 1-[4-(2-ethylmorpholine)]-5-benzyloxy-3-(1-naphthoyl) pyrridopyridine as a yellow powder.

MS: 492 (M+1).⁺

^{IR: 2900, 1600, 1490, 1250, 1100,
1000, 950, 880, 720.}

¹H NMR (300 MHz, CDCl₃): 2.55-3.2 (m, 4H, 2 x CH₂), 3.4-4.01 (m, 8H, 4 x CH₂), 4.43 (s, 2H, OCH₂), 7.7-8.9 (m, 14H, 14 x ArH).

HPLC retention time = 2.76 minutes Isocratic conditions 50 B:50 D (B = 90 % CH₃CN/10 % H₂O /(D = 0.1 % TFA in H₂O) using Zorbax 4.6 mm x 250 mm.

References

1. Ward, S. J.; Mastriani, D.; Casiano, F.; Arnold, R. J. Pharmacol. Exp. 1990, 255, 1230-1239.

2. Bell, M. R.; D'Ambra, T. E.; Kumar, V.; Eissenstat, M. A.; Herrmann, J. L.; Wetzel, J. R.; Rosi, D.; Philion, R. E.; Daum, S. J.; Hlasta, D. J.; Kullnig, R. K.; Ackerman, J. H.; Haubrich, D. R.; Luttinger, D. A.; Baizman, E. R.; Miller, M. S.; Ward, S. J. J. Med. Chem. 1991, 34, 1099-1110.

3. Ward, S. J.; Miller, M. S.; Luttinger, D. A.; Eissenstat, M. A.; Bell, M. R. Neurosci. Abstr. 1988, 14, 324.

4. D'Ambra, T. E.; Estep, K. G.; Bell, M. R.; Eissenstat, M. A.; Josef, K. A.; Ward, S. J.; Haycock, D. A.; Baizman, E. R.; Casiano, F. M.; Belgin, N. C.; Chippari, S. M.; Grego, J. D.; Kullnig, R. K.; Daley, G. T. J. Med. Chem. 1992, 35, 124-135.

Sample availability: available from the authors and MDPI.

1.	Ward, S. J.; Mastriani, D.; Casiano, F.; Arnold, R. J. Pharmacol. Exp. 1990, 255, 1230-1239.
2.	Bell, M. R.; D'Ambra, T. E.; Kumar, V.; Eissenstat, M. A.; Herrmann, J. L.; Wetzel, J. R.; Rosi, D.; Philion, R. E.; Daum, S. J.; Hlasta, D. J.; Kullnig, R. K.; Ackerman, J. H.; Haubrich, D. R.; Luttinger, D. A.; Baizman, E. R.; Miller, M. S.; Ward, S. J. J. Med. Chem. 1991, 34, 1099-1110.
3.	Ward, S. J.; Miller, M. S.; Luttinger, D. A.; Eissenstat, M. A.; Bell, M. R. Neurosci. Abstr. 1988, 14, 324.
4.	D'Ambra, T. E.; Estep, K. G.; Bell, M. R.; Eissenstat, M. A.; Josef, K. A.; Ward, S. J.; Haycock, D. A.; Baizman, E. R.; Casiano, F. M.; Belgin, N. C.; Chippari, S. M.; Grego, J. D.; Kullnig, R. K.; Daley, G. T. J. Med. Chem. 1992, 35, 124-135.