690
A. Manvar, A. Shah / Tetrahedron 69 (2013) 680e691
CDCl3):
d
7.66 (s, 1H), 6.18 (s, 1H), 5.06 (br s, 2H, NH2 exchangeable),
1.0 mmol) and tryptamine (170 mg, 1.05 mmol). Purification by
column chromatography (dichloromethane/methanol: 100/98/
2/96/4/92/8), yielded the title compound 10l (366 mg, 71%) as
yellow solid; [Anal. Calcd for C24H34N7O4P: C 55.91%, H 6.65%, N
4.68e4.61 (m, 2H), 4.42 (t, 2H), 4.00 (t, 2H), 3.72 (d, J¼7.6 Hz, 2H),
3.46 (q, 2H), 1.67 (q, 2H), 1.30e1.18 (m, 12H), 0.98 (t, 3H). 13C NMR
(100 MHz, CDCl3):
d 160.4, 159.4, 152.1, 143.4, 107.4, 73.2, 71.4
(JCeP¼10 Hz), 67.3, 65.6, 42.6, 23.98, 23.91, 23.87, 23.83, 22.7, 11.6. IR
(KBr disc): 3291, 3179, 3099, 2987, 1649, 1589, 1375, 1281, 1180,
919 cmꢁ1. EI-MS: m/z 414 (Mþ, 30), 385 (19), 343 (18), 301 (25), 235
(57), 219 (100), 192 (60), 177 (19), 163 (35), 150 (55), 135 (20), 43
(64), 41 (23).
19.02%; found:
C
55.97%,
H
6.72%,
N
19.06%]; Rf¼0.36,
mp¼139e140 ꢀC. 1H NMR (400 MHz, CDCl3):
d
8.41 (br s, 1H, NH
exchangeable), 7.91 (s, 1H), 7.59 (d, J¼7.8 Hz, 1H), 7.32 (d, J¼7.9 Hz,
1H), 7.32 (s, 1H), 7.25 (t, 1H), 7.11 (s, 1H), 7.07 (t, 1H), 7.00 (d, 1H),
5.80 (s, 1H), 4.77e4.62 (m, 2H), 4.22 (t, 2H), 3.89 (t, 4H), 3.68 (d,
J¼6.8 Hz, 2H), 3.15 (t, 2H), 1.35e1.20 (m, 12H). 13C NMR (100 MHz,
4.8.9. Diisopropyl{2-[2-amino-6-(n-butylamino)-7H-purine-7-yl]
ethoxy}methylphosphonate (10i). The representative procedure B
was followed using compound 7 (392 mg, 1.0 mmol) and n-butyl-
CDCl3): d 163.2, 161.1, 153.5, 141.6, 137.2, 128.5, 123.4, 121.3, 119.3,
118.9, 112.9, 111.6, 110.2, 72.4 (JCeP¼20 Hz), 71.9, 67.9, 66.6, 43.5,
31.1, 24.21, 24.15, 24.09, 24.05. IR (KBr disc): 3512, 3441, 2965, 1653,
1617, 1367, 1239, 1221, 1147, 929, 792 cmꢁ1. EI-MS: m/z 515 (Mþ, 11),
398 (75), 299 (17), 275 (28), 199 (34), 178 (58), 145 (29), 43 (100).
amine (104 mL, 1.05 mmol). Purification by column chromatography
(dichloromethane/methanol: 100/98/2/96/4/94/6), yielded
the title compound 10i (334 mg 78%) as a yellow solid; [Anal. Calcd
for C18H33N6O4P: C 50.46%, H 7.76%, N 19.61%; found: C 50.55%, H
7.81%, N 19.58%]; Rf¼0.30, mp¼128e130 ꢀC. 1H NMR (400 MHz,
4.8.13. Diisopropyl{2-[2-amino-6-(cyclohexylamino)-7H-purine-7-
yl]ethoxy}methyl-phosphonate (10m). The representative pro-
cedure B was followed using compound 7 (392 mg, 1.0 mmol) and
cyclohexylamine (120 mg, 1.05 mmol). Purification by column
chromatography (dichloromethane/methanol: 100/98/2/96/
4/95/5), yielded the title compound 10m (368 mg, 81%) as a white
solid; [Anal. Calcd for C20H35N6O4P: C 52.85%, H 7.76%, N 18.49%;
found: C 52.89%, H 7.81%, N 18.54%]; Rf¼0.28, mp¼142e143 ꢀC. 1H
CDCl3):
d 7.64 (s, 1H), 6.03 (br s, 1H, NH exchangeable), 4.77 (br s,
2H, NH2 exchangeable), 4.68e4.63 (m, 2H), 4.39 (t, 2H), 4.01 (t, 2H),
3.74 (d, J¼7.2 Hz, 2H), 3.51 (q, 2H), 1.63 (q, 2H), 1.45e1.39 (m, 2H),
1.30e1.20 (m, 12H), 0.97 (t, 3H). 13C NMR (100 MHz, CDCl3):
d 160.4,
159.6, 152.1, 143.1, 107.6, 73.2 (JCeP¼10 Hz), 71.4, 67.3, 65.7, 40.6,
31.7, 29.6, 24.0, 23.9, 23.85, 23.81, 20.2, 13.9. IR (KBr disc): 3319,
3181, 3081, 2985, 1649, 1595, 1371, 1289, 1177, 1113, 949 cmꢁ1. EI-
MS: m/z 428 (Mþ, 35), 385 (26), 343 (24), 301 (29), 249 (62), 233
(100), 206 (60), 191 (25), 177 (31), 163 (41), 150 (55), 135 (24), 108
(13), 95 (19), 43 (64), 41 (29).
NMR (400 MHz, CDCl3):
d
7.63 (s, 1H), 5.79 (d, J¼7.1 Hz, 1H), 4.72 (br
s, 2H, NH2 exchangeable), 4.70e4.59 (m, 2H), 4.35 (t, 2H), 4.07 (t,
3H), 3.74 (d, J¼6.1 Hz, 2H), 2.07 (m, 2H), 1.78e1.65 (m, 3H),
1.49e1.37 (m, 2H), 1.29 (d, 8H), 1.21 (d, 7H). 13C NMR (100 MHz,
CDCl3):
d
161.8, 160.1, 151.6, 143.9, 107.8, 73.2 (JCeP¼15 Hz), 71.8,
4.8.10. Diisopropyl{2-[2-amino-6-(benzylamino)-7H-purine-7-yl]
ethoxy}methylphosphonate (10j). The representative procedure B
was followed using compound 7 (392 mg, 1.0 mmol) and benzyl-
67.8, 65.6, 49.3, 47.6, 33.6, 26.1, 25.3, 24.35, 24.31, 24.2. IR (KBr disc):
3278, 3239, 2979, 1561, 1377, 1289, 1217, 1122, 955 cmꢁ1. EI-MS: m/z
454 (Mþ, 20), 275 (40), 259 (70), 232 (38), 193 (24), 177 (30), 150
(100), 43 (41), 41 (20).
amine (115 mL, 1.05 mmol). Purification by column chromatography
(dichloromethane/methanol: 100/99/1/97/3/95/5), yielded
the title compound 10j (356 mg, 77%) as a yellow solid; [Anal. Calcd
for C21H31N6O4P: C 54.54%, H 6.76%, N 18.17%; found: C 54.59%, H
6.70%, N 18.15%]; Rf¼0.35, mp¼131e133 ꢀC. 1H NMR (400 MHz,
Acknowledgements
The authors are thankful to ‘National Facility for Drug Discovery
through New Chemical Entities (NCEs) Development and In-
strumentation Support to Small Manufacturing Pharma Enterprise’
under Drugs and Pharmaceutical Research Support (DPRS) project
jointly funded by DST (India), Gujarat Industries Commissionerate
(Government of Gujarat), and Saurashtra University, Rajkot (India).
CDCl3):
d 7.65 (s, 1H), 7.37e7.21 (m, 5H), 6.68 (br s, 1H, NH ex-
changeable), 5.09 (br s, 2H, NH2 exchangeable), 4.66e4.52 (m, 2H),
4.39 (t, 2H), 3.95 (t, 2H), 3.68 (s, 2H), 3.53 (d, J¼7.2 Hz, 2H),
1.27e1.22 (m, 12H). 13C NMR (100 MHz, CDCl3):
d 162.3, 161.5, 141.1,
129.2, 128.1, 127.1, 108.0, 72.1 (JCeP¼15 Hz), 71.0, 68.9, 68.1, 42.0,
24.1. IR (KBr disc): 3491, 3278, 3179, 2983, 1630, 1588, 1375, 1278,
1175, 1123, 912 cmꢁ1. EI-MS: m/z 462 (Mþ, 25), 335 (21), 245 (27),
163 (31), 149 (19), 101 (32), 91 (100), 43 (30).
References and notes
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4.8.11. Diisopropyl{2-[2-amino-6-(isopropylamino)-7H-purine-7-yl]
ethoxy}methyl-phosphonate (10k). The representative procedure B
was followed using compound 7 (392 mg, 1.0 mmol) and iso-
propylamine (90
mL, 1.05 mmol). Purification by column chroma-
Jacobson,ˇ K. A. J. Med. Chem. 2010, 53, 3748; (g) Zatloukal, M.; Jorda, R.; Gucky,
ꢁ
ꢀ
ꢁ
ꢀ
ꢀ
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T.; Rezníckova, E.; Voller, J.; Pospísil, T.; Malínkova, V.; Adamcova, H.; Krystof, V.;
tography (dichloromethane/methanol: 100/98/2/96/4/95/5),
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[Anal. Calcd for: C17H31N6O4P: C 49.27%, H 7.54%, N 20.28%; found: C
49.33%, H 7.58%, N 20.33%]; Rf¼0.29, mp¼125e127 ꢀC. 1H NMR
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2. (a) De Clercq, E.; Holy, A.; Rosenberg, I.; Sakuma, T.; Balzarini, J.; Maudgal, P. C.
Nature 1986, 323, 464; (b) De Clercq, E.; Sakuma, T.; Baba, M.; Pauwels, R.;
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Balzarini, J.; Rosenberg, I.; Holy, A. Antiviral Res. 1987, 8, 261; (c) De Clercq, E.
(400 MHz, CDCl3):
d 7.89 (s, 1H), 5.01 (br s, 2H, NH2 exchangeable),
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4.51e4.45 (m, 2H), 4.27 (t, 2H), 3.82 (t, 2H), 3.79 (d, J¼7.9 Hz, 2H),
3.09 (m, 1H), 1.31e1.20 (m, 12H), 0.99 (q, 6H). 13C NMR (100 MHz,
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d
163.2, 160.0, 151.9, 144.3, 109.3, 72.12 (JCeP¼5 Hz), 71.9,
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67.2, 65.9, 43.3, 26.7, 24.16, 24.04, 24.0, 23.9. IR (KBr disc): 3291,
3225, 2974, 1579, 1376, 1245, 1209, 1149, 947 cmꢁ1. EI-MS: m/z 414
(Mþ, 37), 389 (21), 239 (43), 229 (100), 211 (50), 175 (23), 150 (29),
135 (32), 55 (34), 43 (85).
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4.8.12. Diisopropyl{2-[6-(2-(1H-indole-3-yl)ethylamino)-2-amino-
7H-purine-7-yl] ethoxy}methylphosphonate (10l). The representa-
tive procedure B was followed using compound 7 (392 mg,
ꢀ
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