SYNTHESIS OF CARBON-14 ANALOGUE
75
(2 ml) and diethyl ether(10 ml), and the pH of the mixture adjusted to
approximately 8.5 by addition of 1 N aqueous NaOH solution. The crude
product, which precipitated upon cooling the suspension, was crystallized
from ethyl acetate/diethyl ether to give the pure title compound 11 (7.18 mCi,
475 mg) (yield: 67%)
1H-NMR (DMSO-d6, TMS) : d5.21 (d, 1H, J ¼ 6:8 Hz); d7.03–7.25 (m,
3H); d7.43–7.58 (m, 9H); d7.99 (d, 2H, J ¼ 6:8 Hz); d9.27(d, 1H, J ¼ 6:8 Hz);
IR (KBr): 523, 770, 1260, 1383, 1527, 1660, 1705, 2889, 3319, 3462 cmꢀ1
.
N-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-benzamide-
[carboxyl-14C]1
Fresh sodium hydride (60% dispersion in mineral oil, 40 mg, 1 mmol) was
added to a solution of N-(2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzo[e][1,4]-
diazepin-3-yl)-benzamide [carboxyl-14C] 11 (5.37 mCi, 355 mg) in anhydrous
DMF (4 ml) at 08C under a nitrogen atmosphere. After 5 min methyl iodide
(142 mg) was added via a micropipette and the reaction mixture stirred for
5 min. The reaction mixture was then added to a vigorously stirred solution of
water (25 ml) containing aqueous sodium hydrogen sulfate (0.5 ml, 1 N). The
reaction slurry was filtered after 5 min and washed with water, ether and cold
methanol and dried under high vacuum. Recrystallization from ethylacetate/
n-hexane(6:4) gave the pure title compound 1 (4.29 mCi, 295 mg).
1H-NMR (CDCl3 , TMS) : d3.51 (s, 3H, methyl); d5.71 (d, 1H, J ¼ 8 Hz,
CH); d7.38–7.63 (m, 12H); d7.95 (d, 2H, J ¼ 8 Hz, aromatics); d8.03 (d, 1H,
J ¼ 8 Hz, amide NH); IR (KBr): 692, 779, 1516, 1644, 1690, 3052, 3278 cmꢀ1
.
Acknowledgements
We gratefully acknowledge the help of Dr R. Dowlatabadi (Tehran University
of Medical Science, Faculty of Pharmacy) and Mr N. Ali-Reza Zadeh (AEOI)
1
for H-NMR spectroscopy and radioactivity determination of synthesized
samples, respectively.
References
1. Henke BR, Aquino CJ, Birkemo LS, Croom DK, Dougherty RW, Ervin Jr GN,
Grizzle MK, Hirst GC, James MK, Johnson MF, Queen KL, Sherrill RG,
Sugg EE, Suh EM, Szewczyk JW, Unwalla RJ, Yingling J, Willson TM. J Med
Chem 1997; 40: 2706–2725.
2. Sherrill RG, Sugg EE. J Org Chem 1995; 60: 730–734.
3. Bock MG, DiPardo RM, Evans BE, Rittle KE, Whitter WL, Garsky VM,
Gilbert KF, Leighton JL, Carson KL, Mellin EC, Veber DF, Chang RSL,
Lotti VJ, Freedman SB, Smith AJ, Patel S, Anderson PS, Freidinger RM. J Med
Chem 1993; 36: 4276–4292.
4. Pullen RGL, Hodgson OJ. J Pharm Pharmacol 1987; 39: 863–864.
Copyright # 2005 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2006; 49: 71–76