A. M. Cuadro et al./Bioorg. Med. Chem. 6 (1998) 173±180
179
3.10.1 2,6-Di-tert-butyl-4-[(4-methyl-pyrimidin-2-yl)-
hydrazonomethyl]phenol (4h)
3.10.5 2,6-Di-tert-butyl-4-[(4-methyl-6-phenyl-
pyrimidin-2-yl)-hydrazonomethyl]phenol (4l)
The procedure B was applied to 2-hydrazino-4-
methylpyrimidine (0.55 g, 4.4 mmol), and after stirring
the mixture for 48 h, 1.21 g (89%) of 4h were obtained as
colourless prisms: mp 194±195ꢀC (hexane:EtAcO); IR
Following the procedure B, with 2-hydrazino-4-
methyl-6-phenylpyrimidine (0.80 g, 4 mmol), 4l (1.49 g,
90%) was obtained as pale-green prisms: mp 200±201ꢀC
(hexane:EtOAc); IR (KBr): 2956, 1585, 1550, 1459,
1
(KBr): 2956, 1590, 1566, 1460, 1431, 1362, 1322,
1
1438, 1367, 1345, 1232 cm 1; H NMR (CDCl3) ꢁ 8.42
1211 cm
;
1H NMR (CDCl3) ꢁ 8.34 (s, 1H), 8.30 (d,
(s, 1H), 8.05±8.01 (m, 2H), 7.79 (s, 1H), 7.51 (s, 2H),
7.43±7.41 (m, 3H), 7.01 (s, 1H), 5.36 (s, 1H), 2.48 (s,
3H), 1.43 (s, 18H) ppm. Anal. calcd for C26H32N4O: C,
74.97; H, 7.74; N, 13.45. Found: C, 75.05; H, 8.00; N,
13.50.
1H, J 5:1 Hz), 7.83 (s, 1H), 7.53 (s, 2H), 6.61 (d, 1H,
J 5:1 Hz), 5.42 (s, 1H), 2.44 (s, 3H), 1.47 (s, 18H)
ppm. Anal. calcd for C20H28N4O: C, 70.56; H, 8.29; N,
16.46. Found: C, 70.58; H, 8.52; N, 16.68.
3.10.2 2,6-Di-tert-butyl-4-[(4,6-dimethyl-pyrimidin-2-
yl)-hydrazonomethyl]phenol (4i)
References
Following the procedure B with 2-hydrazino-4,6-
dimethylpyrimidine (0.61 g, 4.4 mmol), and after stirring
the mixture at room temperature for 16 h, 0.98 g (69%)
of 4i were obtained as colourless prisms: mp 181±182ꢀC
(hexane:EtOAc); IR (KBr): 2957, 1592, 1559, 1456,
1434, 1370, 1336 cm 1; 1H NMR (CDCl3) ꢁ 8.34 (s, 1H),
7.79 (s, 1H), 7.51 (s, 2H), 6.49 (s, 1H), 5.41 (s, 1H), 2.40
(s, 6H), 1.45 (s, 18H) ppm. Anal. calcd for C21H30N4O:
C, 71.15; H, 8.53; N, 15.80. Found: C, 71.42; H, 8.55; N,
15.79.
[1] (a) Sam S, Chan H, LeRiche JC, Chan-Yeung M, Salari
H. J Allergy Clin Immunol 1988;81:711. (b) Bisgaard H,
Dan Med Bull 1989;36:142. (c) Ruzicka T. Clin Res
1989;37:R14. (d) Wallace JL. Trends Pharmacol Sci
1990;11:51.
[2] Ford-Hutchinson AW. Crit Rev Immunol 1990;10:1.
[3] (a) Arm JP, Spur BW, Lee TH. Am Rev Resp Dis
1991;144:1053. (b) Lefer AM. Biochem Pharmacol
1986;35:439. (c) Bray MA, Cunningham FM, Ford-
Hutchinson AW, Smith MJH. Br
1981;72:483. (d) Iacopino VJ, Fitzpatrick TM, Ramwell
J
Pharmacol
PW, Rose JC, Kot PA.
1983;227:483.
[4] (a) Redkar-Brown DG, Aharony D. Eur J Pharmacol
1989;165:113. (b) Jones TR, Charette L, Denis D. Br J
Pharmacol 1988;95:309.
J Pharmacol Exptl Ther
3.10.3 2,6-Di-tert-butyl-4-[(4-butyl-pyrimidin-2-yl)-
hydrazonomethyl]phenol (4j)
Following the procedure B with 4-butyl-2-hydrazino-
pyrimidine (0.73 g, 4.4 mmol) and after stirring the mix-
ture for 3 h and isolating the product by column
chromatography (hexane: EtOAc 8:2), 4j (1.30 g, 85%)
was obtained as colourless prisms: mp 134±135ꢀC (hex-
ane); IR (KBr): 3625, 2956, 2871, 1570, 1409, 1231,
[5] Denzlinger C, Grimberg M, Kapp A, Wilmanns W. J
Allergy Clin Immunol 1990;85:218.
[6] (a) Unangst PC, Shrum GP, Connor DT, Dyer RD,
Schrier DJ. J Med Chem 1992;35:3691. (b) Mullican
MD, Wilson MW, Connor DT, Kostlan CR, Schrier
DJ, Dyer RD. J Med Chem 1993;36:1090. (c) Lazer ES,
Wong HC, Possanza GJ, Graham AG, Farina PR. J
Med Chem 1989;32:100. (d) Flynn DL, Belliotti TR,
Boctor AM, Connor DT, Kostlan CR, Nies DE, Ortwine
DF, Schrier DJ, Sircar JC. J Med Chem 1991;34:518. (e)
Unangst PC, Connor DT, Cetenko WA, Sorenson RJ,
Kostlan CR, Sircar JC, Wright CD, Schrier DJ, Dyer RD.
J Med Chem 1994;37:322. (f) Kramer JB, Capiris T,
Sircar JC, Connor DT, Bornemeier DA, Dyer RD,
Kuipers PJ, Kennedy JA, Wright CD, Okonkwo GCN,
Lesch ME, Schrier DJ, Boschelli DH. Bioorg Med Chem
1995;3:403.
1
1157, 1124 cm 1; H NMR (CDCl3) ꢁ 8.35 (s, 1H), 8.33
(d, 1H, J 5:1 Hz), 7.83 (s, 1H), 7.53 (s, 2H), 6.60 (d,
1H, J 5:1 Hz), 5.42 (s, 1H), 2.66 (t, 2H, J 7:7 Hz),
1.79±1.63 (m, 2H), 1.50±1.35 (m, 20H, 18H), 0.95 (t, 3H,
J 7:3 Hz) ppm. Anal. calcd for C23H34N4O: C,
72.21; H, 8.96; N, 14.65. Found: C, 71.91; H, 9.04; N,
14.62.
3.10.4 2,6-Di-tert-butyl-4-[(4,6-dibutyl-pyrimidin-2-yl)-
hydrazonomethyl]phenol (4k)
[7] (a) Matsukawa T, Ohta B.
J Pharm Soc Japan
Following the procedure B, with 4,6-dibutyl-2-hydra-
zinopyrimidine (0.98 g, 4.4 mmol), the mixture was stir-
red at room temperature for 1 h. Puri®cation by
chromatography (hexane: EtOAc, 9:1) gave 4k (1.49 g,
85%) as pale-green prisms: mp 126±127ꢀC (hexane); IR
(KBr): 2957, 2869, 1556, 1433, 1368, 1216, 1110 cm
1949;69:489. (b) Hauser CH, Manyik RM. J Org Chem
1953;18:588. (c) Harden DB, Mokrosz MJ, Strekowski
LJ. Org Chem 1988;53:4137. (d) Strekowski L, Harden
DB, Grubb WB, Patterson SE, Czarny A, Mokrosz MJ,
Cegla MT, Wydra RL. J Heterocyclic Chem 1990;27:1393.
[8] (a) Katz L. J Am Chem Soc 1951;73:4007. (b) Katz L. J
Am Chem Soc 1953;75:712. (c) Matsukawa T, Ban S,
1
;
1H NMR (CDCl3) 8.28 (s, 1H), 7.80 (s, 1H), 7.51 (s,
2H), 6.48 (s, 1H), 5.38 (s, 1H), 2.64 (t, 4H, J 7:8 Hz),
1.76±1.64 (m, 4H), 1.50±1.34 (m, 22H, 18H terbut+4H-
CH2-), 0.94 (t, 6H, J 7:3 Hz) ppm. Anal. calcd for
C27H42N4O: C, 73.93; H, 9.65; N, 12.77. Found: C,
73.67; H, 9.90; N, 12.82.
Shirakawa K, Yoneda M.
1953;75:159. (d) Claesen M. Bull Soc Chim Belg
1959;68:30.
J
Pharm Soc Japan
[9] (a) Samuelsson B, Funk CD. J Biol Chem 1989;264:19469.
(b) Lewis RA, Austen KF, Soberman RJ. New Eng J Med
1990;323:645.
[10] Klotz IM. Science 1982;107:220.