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E. Goßnitzer et al. / European Journal of Pharmaceutical Sciences 15 (2002) 49–61
54
2.2.4.8. s-trans-4-Isopropyl-6-phenyl-2-h2-[(E)-1-
phenylbutylidene]-(E)-hydrazinoj-1,4-dihydropyrimidine
hydrochloride (13h?HCl)
1654s, 1602s, 1514s, 1499m, 1448m, 1307m, 1273s,
1112m, 975m; H NMR ([D6]DMSO): d50.92 and 0.96
1
and 1.99 (d, J56.4 Hz, 3H, and d, J56.4 Hz, 3H, and
octet, J56.4 Hz, 1H, (CH3)2CH), 2.33 (s, 3H, CH3,
4-CH3C6H4), 2.44 (s, 3H, CH3C=N), 4.23 (dd, J56.4 Hz,
4.0 Hz, 1H, H-4), 5.50 (d, J54.0 Hz, 1H, H-5), 7.27 and
7.64 (AA9XX9, J58.0 Hz, 232H, H-3/5 and H-2/6,
4-CH3C6H4), 7.43 (m, 3H, p-H and m-H, C6H5), 8.00 (dd,
J58.2 Hz, 2.4 Hz, 2H, o-H, C6H5), 9.05 (s, broad, 1H,
N3H), 10.86 (s, broad, 1H, N1H), 12.12 (s, 1H, N2H) ppm;
13C NMR ([D6]DMSO): d515.9 (CH3), 17.1 and 34.6
((CH3)2CH), 20.7 (CH3, 4-CH3C6H4), 55.2 (C-4), 98.4
(C-5), 124.9 (o-C, C6H5), 126.9 (C-2/6, 4-CH3C6H4),
128.3 (m-C, C6H5), 128.3 (C-3/5, 4-CH3C6H4), 129.9
( p-C, C6H5), 132.4 (C-1, C6H5), 133.3 (C-6), 136.6 (C-4,
4-CH3C6H4) 139.0 (C-1, 4-CH3C6H4), 151.0 (C-2), 153.4
(C=N) ppm. Anal. Calc. for C22H27ClN4 (382.92): C,
69.00; H, 7.11; Cl, 9.26; N, 14.63. Found: C, 69.12; H,
6.99; Cl, 9.10; N, 14.50.
Yield: 4.51 g (56.8%); m.p. 1778C (cyclohexane/etha-
nol); TLC (ES 1): Rf50.58; IR (cm21): 3397m, 3183m,
3059m, 2962m, 2929s, 2873m, 1658s, 1609s, 1498m,
1466m, 1245m, 1107m, 764m, 693m; 1H NMR
([D6]DMSO): d50.94 and 0.96 and 2.00 (d, J56.8 Hz,
3H, and d, J56.8 Hz, 3H, and octet, J56.8 Hz, 1H,
(CH3)2CH), 1.00 and 1.52 and 2.95 (t, J57.2 Hz, 3H, and
sextet, J57.2 Hz, 2H, and t, J57.2 Hz, 2H,
CH3CH2CH2), 4.25 (dd, J56.8 Hz, 4.0 Hz, 1H, H-4), 5.56
(d, J54.0 Hz, 1H, H-5), 7.45 (m, 6H, p-H and m-H,
23C6H5), 7.77 (d, J56.2 Hz, 2H, o-H, 6-C6H5), 7.99 (dd,
J57.6 Hz, 2.8 Hz, 2H, o-H, C6H5C=N), 9.01 (s, broad,
1H, N3H), 11.09 (s, broad, 1H, N1H), 12.35 (s, 1H, N2H)
ppm; 13C NMR ([D6]DMSO): d513.6 and 19.7 and 29.0
(CH3CH2CH2), 17.1 and 34.6 ((CH3)2CH), 55.2 (C-4),
99.2 (C-5), 125.0 (o-C, 6-C6H5), 127.0 (o-C, C6H5C=N),
128.4 (m-C, 6-C6H5), 128.8 (m-C, C6H5C=N), 129.3 ( p-
C, 6-C6H5), 129.9 ( p-C, C6H5C=N), 132.0 (C-1, 6-C6H5),
133.4 (C-6), 135.6 (C-1, C6H5C=N), 151.1 (C-2), 156.7
(C=N) ppm. Anal. Calc. for C23H29ClN4 (396.95): C,
69.59; H, 7.36; Cl, 8.93; N, 14.12. Found: C, 69.62; H,
7.29; Cl, 8.73; N, 13.98.
2.2.4.11. s-trans-4-Isopropyl-6-(4-methoxyphenyl)-2-h2-
[(E)-1-phenylethylidene]-(E)-hydrazinoj-1,4-dihydro-
pyrimidine hydrochloride (15a?HCl)
Yield: 3.68 g (46.1%); m.p. 2308C; TLC (ES 1): Rf5
0.64; IR (cm21): 3422m, 3179m, 3060m, 2964m, 2930m,
1662s, 1609s, 1513s, 1306m, 1281m, 1030m, 830m; 1H
NMR ([D6]DMSO): d50.93 and 0.96 and 1.98 (d, J56.8
Hz, 3H, and d, J56.8 Hz, 3H, and octet, J56.8 Hz, 1H,
(CH3)2CH), 2.45 (s, 3H, CH3C=N), 3.80 (s, 3H, OCH3),
4.22 (dd, J56.8 Hz, 4.4 Hz, 1H, H-4), 5.43 (d, J54.4 Hz,
1H, H-5), 7.01 and 7.70 (AA9XX9, J58.8 Hz, 232H,
H-3/5 and H-2/6, 4-CH3OC6H4), 7.45 (m, 3H, p-H and
m-H, C6H5), 8.0 (dd, J57.2 Hz, 3.6 Hz, 2H, o-H, C6H5),
9.03 (s, broad, 1H, N3H), 10.82 (s, broad, 1H, N1H), 12.09
(s, 1H, N2H) ppm; 13C NMR ([D6]DMSO): d515.1
(CH3), 17.1 and 34.6 ((CH3)2CH), 55.1 (C-4), 55.3
(OCH3), 97.3 (C-5), 114.1 (C-3/5, 4-CH3OC6H4), 126.5
(C-2/6, 4-CH3OC6H4), 126.9 (o-C, C6H5), 128.3 (m-C,
C6H5), 129.9 ( p-C, C6H5), 133.0 (C-1, C6H5), 133.6
(C-6), 137.0 (C-1, 4-CH3OC6H4), 151.0 (C-2), 153.4
(C=N), 160.1 (C-4, 4-CH3OC6H4) ppm. Anal. Calc. for
C22H27ClN4O (398.92): C, 66.23; H, 6.82; Cl, 8.89; N,
14.05. Found: C, 66.15; H, 6.80; Cl, 8.80; N, 14.00.
2.2.4.9. s-trans-4-Isopropyl-6-phenyl-2-h2-[(E)-1-
phenylpentylidene]-(E)-hydrazinoj-1,4-dihydropyrimidine
hydrochloride (13i?HCl)
Yield: 3.45 g (42.0%); m.p. 1788C (cyclohexane/etha-
nol); TLC (ES 1): Rf50.67; IR (cm21): 3406m, 3058m,
2959m, 2930m, 1662s, 1607s, 1498m, 1281w, 1105w,
764m, 694m; 1H NMR ([D6]DMSO): d50.87 and 1.46
and 2.94 (t, J57.2 Hz, 3H, and m, 4H, and t, J57.2 Hz,
2H, CH3CH2CH2CH2), 0.94 and 0.97 and 2.00 (d, J56.8
Hz, 3H, and d, J56.8 Hz, 3H, and octet, J56.8 Hz, 1H,
(CH3)2CH), 4.25 (dd, J56.8 Hz, 4.0 Hz, 1H, H-4), 5.56
(d, J54.0 Hz, 1H, H-5), 7.46 (m, 6H, p-H and m-H,
23C6H5), 7.74 (d, J56.8 Hz, 2H, o-H, 6-C6H5), 7.98 (dd,
J56.8 Hz, 2.8 Hz, 2H, o-H, C6H5C=N), 9.01 (s, broad,
1H, N3H), 10.84 (s, broad, 1H, N1H), 12.05 (s, 1H, N2H)
ppm; 13C NMR ([D6]DMSO): d513.7 and 22.0 and 27.2
and 29.0 (CH3CH2CH2CH2), 17.1 and 34.6 ((CH3)2CH),
55.2 (C-4), 99.2 (C-5), 125.1 (o-C, 6-C6H5), 127.0 (o-C,
C6H5C=N), 128.5 (m-C, 6-C6H5), 128.8 (m-C,
C6H5C=N), 129.4 ( p-C, 6-C6H5), 129.9 ( p-C,
C6H5C=N), 133.4 (C-6), 135.7 (C-1, 6-C6H5), 143.5 (C-1,
C6H5C=N), 151.0 (C-2), 156.9 (C=N) ppm. Anal. Calc.
for C24H31ClN4 (410.98): C, 70.14; H, 7.60; Cl, 8.63; N,
13.64. Found: C, 70.05; H, 7.55; Cl, 8.42; N, 13.58.
2.2.4.12. s-trans-6-(4-Chlorophenyl)-4-isopropyl-2-h2-
[(E)-1-phenylethylidene]-(E)-hydrazinoj-1,4-dihydro-
pyrimidine hydrochloride (16a?HCl)
Yield: 3.45 g (42.8%); m.p. 2378C (ethanol/cyclohex-
ane); TLC (ES 1): Rf50.53; IR (cm21): 3429m, 3188m,
3064w, 2962m, 2927m, 1661s, 1611s, 1495m, 1444m,
1398m, 1099m, 828m, 762m; 1H NMR ([D6]DMSO):
d50.93 and 0.96 and 2.00 (d, J56.8 Hz, 3H, and d, J56.8
Hz, 3H, and octet, J56.8 Hz, 1H, (CH3)2CH), 2.44 (s, 3H,
CH3C=N), 4.24 (dd, J56.8 Hz, 4.4 Hz, 1H, H-4), 5.61 (d,
J54.4 Hz, 1H, H-5), 7.45 (m, 3H, p-H and m-H, C6H5),
2.2.4.10. s-trans-4-Isopropyl-6-(4-methylphenyl)-2-h2-
[(E)-1-phenylethylidene]-(E)-hydrazinoj-1,4-dihydro-
pyrimidine hydrochloride (14a?HCl)
Yield: 3.82 g (49.9%); m.p. 2258C; TLC (ES 1): Rf5
0.58; IR (cm21): 3401m, 3362m, 3061m, 2959m, 1680s,