RCHH HARM
A P
Arch. Pharm. Chem. Life Sci. 2015, 348, 229–241
8-Amino-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione Derivatives
Archiv der Pharmazie
NC6H4OCH3), 7.07 (s, 2H, NH2), 9.90–10.10 (s, 1H, NHþ). LC/MS:
m/z calc. 428.24, found 428.36. Anal. (C21H28ClN7O3) C, H, N.
3H, N(3)CH3), 3.44–3.48 (m, 2H, CH2NHþ(CH2CH2)2N), 3.51–3.55
(m, 2H, CH2NHþ(CH2CH2)2N), 3.77 (s, 3H, OCH3), 4.14 (t,
3J ¼ 7.0 Hz, 2H, N(7)CH2), 6.85–7.03 (m, 4H, NC6H4OCH3), 7.20
(s, 1H, NHCH3), 10.80–10.95 (s, 1H, NHþ). LC/MS: m/z calc.
442.26, found 442.34. Anal. (C22H32ClN7O3) C, H, N.
8-Amino-1,3-dimethyl-7-(3-(4-(3-chlorophenyl)piperazin-1-
yl)propyl)-1H-purine-2,6(3H,7H)-dione hydrochloride (36)
From 15 in 93% yield: m.p. 290–292°C, Rf ¼ 0.22 (A), 0.52 (B), 1H
NMR d 2.00–2.15 (m, 2H, CH2CH2CH2), 3.00–3.17 (m, 6H,
CH2NHþ(CH2CH2)2N), 3.17 (s, 3H, N(1)CH3), 3.32 (s, 3H, N(3)
CH3), 3.53–3.60 (m, 2H, CH2NHþ(CH2CH2)2N), 3.86–3.89 (m, 2H,
CH2NHþ(CH2CH2)2N), 4.10 (t, 3J ¼ 6.7 Hz, 2H, N(7)CH2), 6.85 (dd,
3J ¼ 7.7 Hz, 4J ¼ 1.8 Hz, 1H, 6-NC6H4Cl), 6.94 (dd, 3J ¼ 8.4 Hz,
4J ¼ 1.9 Hz, 1H, 4-NC6H4Cl), 7.03 (t, 4J ¼ 2.2 Hz, 1H, 2-NC6H4Cl),
7.07 (s, 2H, NH2), 7.24 (t, 3J ¼ 8.2 Hz, 1H, 5-NC6H4Cl), 10.00–
10.20 (s, 1H, NHþ). LC/MS: m/z calc. 432.19, found 432.24. Anal.
(C20H27Cl2N7O2) C, H, N.
1,3-Dimethyl-8-(methylamino)-7-(3-(4-(3-chlorophenyl)-
piperazin-1-yl)propyl)-1H-purine-2,6(3H,7H)-dione
hydrochloride (41)
From 10 in 76% yield: m.p. 301–303°C, Rf ¼ 0.19 (A), 0.54 (B), 1H
NMR (base) d 2.05–2.15 (m, 2H, CH2CH2CH2), 2.37 (t, 3J ¼ 6.2 Hz,
2H, CH2N(CH2CH2)2N), 2.62 (t, 3J ¼ 4.9 Hz, 4H, CH2N-
(CH2CH2)2N), 3.03 (d, 3J ¼ 4.9 Hz, 3H, NHCH3), 3.26
(t, 3J ¼ 4.9 Hz, 4H, CH2N(CH2CH2)2N), 3.37 (s, 3H, N(1)CH3),
3.54 (s, 3H, N(3)CH3), 4.04 (t, 3J ¼ 5.6 Hz, 2H, N(7)CH2), 6.81
(ddd, 3J ¼ 8.5 Hz, 4J ¼ 2.4 Hz, 5J ¼ 0.8 Hz, 1H, 6-NC6H4Cl), 6.86
(ddd, 3J ¼ 8.0 Hz, 4J ¼ 2.0 Hz, 5J ¼ 0.8 Hz, 1H, 4-NC6H4Cl), 6.90
(t, 4J ¼ 2.0 Hz, 1H, 2-NC6H4Cl), 7.14–7.18 (m, 1H, NHCH3), 7.17
(t, 3J ¼ 8.1 Hz, 1H, 5-NC6H4Cl). LC/MS: m/z calc. 446.21, found
446.35. Anal. (C21H29Cl2N7O2) C, H, N.
8-Amino-1,3-dimethyl-7-(3-(4-(4-fluorophenyl)piperazin-1-
yl)propyl)-1H-purine-2,6(3H,7H)-dione hydrochloride (37)
From 16 in 93% yield: m.p. 292–294°C, Rf ¼ 0.21 (A), 0.48 (B), 1H
NMR d 2.00–2.15 (m, 2H, CH2CH2CH2), 2.96 (t, 3J ¼ 12.2 Hz, 2H,
CH2NHþ(CH2CH2)2N), 3.05–3.17 (m, 4H, CH2NHþ(CH2CH2)2N),
3.17 (s, 3H, N(1)CH3), 3.33 (s, 3H, N(3)CH3), 3.54–3.58 (m, 2H,
CH2NHþ(CH2CH2)2N), 3.70–3.74 (m, 2H, CH2NHþ(CH2CH2)2N),
4.10 (t, 3J ¼ 6.5 Hz, 2H, N(7)CH2), 6.97–7.11 (m, 6H, NC6H4F,
NH2), 9.08–10.00 (s, 1H, NHþ). LC/MS: m/z calc. 416.22, found
416.32. Anal. (C20H27ClFN7O2) C, H, N.
8-(Ethylamino)-1,3-dimethyl-7-(3-(4-phenylpiperazin-1-yl)-
propyl)-1H-purine-2,6(3H,7H)-dione hydrochloride (42)
From 11 in 69% yield: m.p. 286–287°C, Rf ¼ 0.17 (A), 0.50 (B), 1H
NMR (base) d 1.19 (t, 3J ¼ 7.0 Hz, 3H, NHCH2CH3), 2.05–2.15 (m,
2H, CH2CH2CH2), 2.38 (t, 3J ¼ 6.1 Hz, 2H, CH2N(CH2CH2)2N), 2.62
(m, 4H, CH2N(CH2CH2)2N), 3.14 (m, 4H, CH2N(CH2CH2)2N), 3.36
(s, 3H, N(1)CH3), 3.47 (q, 3J ¼ 7.0 Hz, 2H, NHCH2CH3), 3.53 (s, 3H,
N(3)CH3), 4.06 (t, 3J ¼ 7.0 Hz, 2H, N(7)CH2), 6.83 (t, 3J ¼ 7.0 Hz,
1H, p-NC6H5), 6.96 (d, 3J ¼ 8.5 Hz, 2H, o-NC6H5), 7.25 (t,
3J ¼ 8.0 Hz, 2H, m-NC6H5), 7.26 (t, 3J ¼ 6.0 Hz, 1H, NH CH2CH3).
LC/MS: m/z calc. 426.26, found 426.38. Anal. (C22H32ClN7O2) C,
H, N.
8-Amino-7-(3-(3,4-dihydroisoquinolin-2(1H)-yl)propyl)-1,3-
dimethyl-1H-purine-2,6(3H,7H)-dione hydrochloride (38)
From 17 in 56% yield: m.p. 266–268°C, Rf ¼ 0.19 (A), 0.46 (B), 1H
NMR d 2.05–2.20 (m, 2H, CH2CH2CH2), 2.85–3.19 (m, 4H,
CH2NHþTHIQ, 4,4-THIQ), 3.18 (s, 3H, N(1)CH3), 3.35 (s, 3H, N(3)
CH3), 3.45–3.60 (m, 2H, 3,3-THIQ), 4.10–4.20 (m, 1H, 1-THIQ),
4.14 (t, 3J ¼ 7.1 Hz, 2H, N(7)CH2), 4.40–4.50 (m, 1H, 1-THIQ),
7.08 (s, 2H, NH2), 7.10–7.26 (m, 4H, 5,6,7,8-THIQ), 10.00–10.20
(s, 1H, NHþ). LC/MS: m/z calc. 396.20, found 369.37. Anal.
(C19H25ClN6O2) C, H, N.
8-(Ethylamino)-1,3-dimethyl-7-(3-(4-(2-methoxyphenyl)-
piperazin-1-yl)propyl)-1H-purine-2,6(3H,7H)-dione
hydrochloride (43)
From 12 in 65% yield: m.p. 286–287°C, Rf ¼ 0.13 (A), 0.48 (B), 1H
NMR (base) d 1.26 (t, 3J ¼ 7.2 Hz, 3H, NHCH2CH3), 2.09–2.16 (m,
2H, CH2CH2CH2), 2.39 (t, 3J ¼ 6.0 Hz, 2H, CH2N(CH2CH2)2N), 2.68
(m, 4H, CH2N(CH2CH2)2N), 3.15 (m, 4H, CH2N(CH2CH2)2N), 3.38
(s, 3H, N(1)CH3), 3.47 (q, 3J ¼ 7.0 Hz, 2H, NHCH2CH3), 3.53 (s, 3H,
1,3-Dimethyl-8-(methylamino)-7-(3-(4-phenylpiperazin-1-
yl)propyl)-1H-purine-2,6(3H,7H)-dione hydrochloride (39)
From 8 in 60% yield: m.p. 281–283°C, Rf ¼ 0.17 (A), 0.54 (B), 1H
NMR d 2.00–2.15 (m, 2H, CH2CH2CH2), 2.89 (s, 3H, NHCH3), 3.08–
3.17 (m, 6H, CH2NHþ(CH2CH2)2N), 3.18 (s, 3H, N(1)CH3), 3.36 (s,
3H, N(3)CH3), 3.54–3.56 (m, 2H, CH2NHþ(CH2CH2)2N), 3.76–3.79
3
N(3)CH3), 3.88 (s, 3H, OCH3), 4.04 (t, J ¼ 5.7 Hz, 2H, N(7)CH2),
6.88–7.08 (m, 4H, NC6H4OCH3), 7.23 (t, 3J ¼ 5.3 Hz, 1H,
NHCH2CH3). LC/MS: m/z calc. 456.27, found 456.38. Anal.
(C23H34ClN7O3) C, H, N.
3
(m, 2H, CH2NHþ(CH2CH2)2N), 4.13 (t, J ¼ 7.0 Hz, 2H, N(7)CH2),
6.84 (t, 3J ¼ 7.2 Hz, 1H, p-NC6H5), 6.98 (d, 3J ¼ 7.0 Hz, 2H, o-
NC6H5), 7.24 (t, 3J ¼ 8.0 Hz, 2H, m-NC6H5), 7.35 (s, 1H, NHCH3),
10.50–10.70 (s, 1H, NHþ). LC/MS: m/z calc. 412.24, found 412.35.
Anal. (C21H30ClN7O2) C, H, N.
8-Amino-1,3-dimethyl-7-(4-(4-phenylpiperazin-1-yl)butyl)-
1H-purine-2,6(3H,7H)-dione hydrochloride (44)
From 24 in 94% yield: m.p. 252–254°C, Rf ¼ 0.06 (A), 0.26 (B), 1H
NMR d 1.60–1.80 (m, 4H, N(7)CH2CH2CH2CH2), 3.05–3.15 (m,
6H, CH2NHþ(CH2CH2)2N), 3.16 (s, 3H, N(1)CH3), 3.31 (s, 3H, N(3)
CH3), 3.48–3.50 (m, 2H, CH2NHþ(CH2CH2)2N), 3.77–3.80 (m, 2H,
CH2NHþ(CH2CH2)2N), 4.00–4.05 (m, 2H, N(7)CH2), 6.84 (t,
3J ¼ 7.3 Hz, 1H, p-NC6H5), 6.98 (d, 3J ¼ 7.7 Hz, 2H, o-NC6H5),
7.24 (t, 3J ¼ 8.0 Hz, 2H, m-NC6H5), 6.90–7.30 (s, 2H, NH2), 10.60–
1,3-Dimethyl-8-(methylamino)-7-(3-(4-(2-methoxyphenyl)-
piperazin-1-yl)propyl)-1H-purine-2,6(3H,7H)-dione
hydrochloride (40)
From 9 in 50% yield: m.p. 287–289°C, Rf ¼ 0.13 (A), 0.44 (B), 1H
NMR d 2.00–2.20 (m, 2H, CH2CH2CH2), 2.89 (s, 3H, NHCH3), 3.02–
3.17 (m, 6H, CH2NHþ(CH2CH2)2N), 3.17 (s, 3H, N(1)CH3), 3.38 (s,
ß 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
239