496 Journal of Medicinal Chemistry, 1975, Vol. 18, No. 5
U u u m , Martini, Kullnig, Clarke
7.73 (m, 4, C&), 7.12 (s, 2, “21, 8.17 (d, 1, NH), 8.58 (s, 1, 7Acknowledgments. This investigation was supported CH 1. Anal. (C~oH21N705S.0.9 HC1.0.2H20) C, H, C1, N, S. by the Division of Cancer Treatment, National Cancer InN-b-[ [ [2-Amino-4-(methylthio)-6-pteridinyl]methyl]methylstitute, National Institutes of Health, Department of amino]benzoyl]-L-glutamic Acid (22). Methyl iodide (0.014 Health, Education and Welfare, Contract N01-CM-43762. ml, 0.217 mmol) was added (Hamilton micro syringe) to a stirred The authors are indebted to Dr. W. C. Coburn, Jr., and solution of 21 (100 mg, 0.197 mmol) in 1 N NaOH (0.767 ml) and members of the Molecular Spectroscopy Section of SouthH20 (2.7 ml) a t 0’. The mixture was stirred for 1 hr a t 0’ and 18 hr a t 25’. Acidification of the resulting solution with 1 N HCl to p H ern Research Institute, who performed most of the mi2.5 gave an orange precipitate which was collected by filtration, croanalytical and spectral determinations reported. washed with H20 a t pH 2.5, and dried in vacuo a t 65’ ( P 2 0 5 ) : yield , , , ,A nm ( t X (solvent c), 0.1 N HC1, 308 (22.91, 90 mg (90%); pH 7, 275 (22.4), 303 (25.2), 3P5 362 (9.90), 377 (sh, 8.63);, , ,A (8.36); , , ,A 0.1 N NaOH, 275 (21.6), 303 (25.3), 384 (8.99); urnax 1710, 1600,1550, and 1505 cm-l; ‘H NMR 6 1.8-2.4 (m, CHzCHz), References and Notes 2.56 (s, SCH3), 3.24 (s, 3, NCHs), 4.36 (m, NCH), 4.86 (s, 2, NCHz), R. L. Blakley, “The Biochemistry of Folic Acid and Related 8.80 (s, 1,7 6.82, 7.74 (m, 4, C&), 7.48 (s, NHz), 8.18 (d, 1, “1, CH). Anal. ( C ~ I H ~ ~ N 1.3H20) ~ O ~ S C, . H, N, S. Pteridines, Frontiers of Biology”, Vol. 13, A. Neuberger and N - [ p-[ [ (2-Amino-4-hydrazino-6-pteridinyl)methyl]methylE. L. Tatum, Ed.. American Elsevier, New York, N.Y., 1969. amino]benzoyl]- glutamic Acid ( 2 3 ) . A solution of 22 (25.0 R. D. Elliott, C. Temple, Jr., J. L. Frye, and 3. A. Montgommg, 0.049mmol) and 85% hydrazine hydrate (57.9 mg, 0.984 mmol) ery, J . Heterocycl. Chem., 10,1071 (1973).
