Synthesis of Acyclic Nucleoside Phosphonates
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(C-5); 86.29 an d 83.56 (C-1′ an d C-2′); 70.55 d, 2 C, J(P,C) = 6.8 (P-OC); 63.51 d, J(P,C) =
166.0 (P-C); 59.76 d, J(P,C) = 15.6 (O-C); 23.99 d, 2 C, J(P,C) = 3.9 an d 23.89 d, 2 C, J(P,C) =
4.9 (CH3).
Com poun d 3 (170 m g, 0.5 m m ol), aceton itrile (10 m l) an d BrSiMe3 (1.0 m l, 7.6 m m ol)
were stirred at room tem perature overn igh t. After evaporation in vacuo an d coevaporation
with aceton itrile, th e residue was treated with water an d trieth ylam in e was added to alkalin e
reaction . Th e m ixture was evaporated to dryn ess an d th e residue was dissolved in h ot water.
Acetic acid was added to ca. pH 6 an d th e product precipitated as wh ite solid (115 m g,
88%), m .p. 290 °C (decom p.). FABMS, m/z (%): 259 (MH+) (60). IR (KBr): 3433, 3354, 3149,
2245, 1860, 1681, 1651, 1617, 1513, 1422, 1217, 1176, 1140, 1009, 941, 767, 593, 524, 455.
1H NMR (D2O + NaOD): 6.16 s, 1 H (H-5); 4.48 s, 2 H (O-CH2); 3.62 d, 2 H, J(P,CH) = 8.8
(P-CH2). 13C NMR (D2O + NaOD): 164.77 (C-4); 162.61 (C-2); 147.87 (C-6); 99.85 (C-5);
87.72 an d 83.65 (C-1′ an d C-2′); 68.36 d, J(P,C) = 149.4 (P-C); 59.75 d, J(P,C) = 12.7
(O-CH2). For C8H11N4O4P·1/3H2O (264.2) calculated: 36.37% C, 4.54% H, 21.21% N,
11.72% P; foun d: 36.53% C, 4.33% H, 20.92% N, 11.72% P.
Reduction of 2,4-Diam in o-6-alkyn ylpyrim idin es. Gen eral Procedure
2,4-Diam in o-6-alkyn ylpyrim idin e7 1 or 2 (5.0 m m ol) was h ydrogen ated at atm osph eric pres-
sure in m eth an ol (100 m l) over 5% palladium on ch arcoal (0.3 g) un der stirrin g at room
tem perature for 20 h . Th e m ixture was filtered th rough a pad of Celite, th e catalyst was
wash ed with h ot water an d h ot m eth an ol (100 m l each ) an d th e filtrate was evaporated.
Crystallisation (aceton e–m eth an ol) afforded required products 6 or 7.
2,4-Diamino-6-(3-hydroxypropyl)pyrimidine (6). Yield 0.63 g (78%) of wh ite solid, m .p.
160–162 °C. FABMS, m/z (%): 169 (MH+) (100). IR (KBr): 3444, 3378, 3176, 2900, 2761,
1644, 1602, 1561, 1436, 1412, 1349, 1205, 1069, 1007, 926, 806, 762, 572, 446. 1H NMR
(DMSO-d6): 6.12 brs, 2 H an d 5.77 brs, 2 H (NH2); 5.50 s, 1 H (H-5); 4.75 brs, 1 H (OH); 3.39 t,
2 H, J(3′,2′) = 7.6 (H-3′); 2.27 t, 2 H, J(1′,2′) = 6.5 (H-1′); 1.67 brpen t, 2 H (H-2′). 13C NMR
(DMSO-d6): 168.56 (C-4); 164.80 (C-2); 163.48 (C-6); 93.00 (C-5); 60.68 (C-3′); 33.78 (C-1′);
31.65 (C-2′). For C7H12N4O·1/6H2O (171.2) calculated: 49.11% C, 7.26% H, 32.73% N;
foun d: 49.12% C, 7.32% H, 32.49% N.
2,4-Diamino-6-(4-hydroxybutyl)pyrimidine (7). Yield 0.66 g (72%) of white solid, m.p. 226–228 °C.
FABMS, m/z (%): 183 (MH+) (100). IR (KBr): 3336, 3179, 2941, 1659, 1620, 1595, 1559, 1525,
1493, 1417, 1266, 1066, 999, 767, 573, 487. 1H NMR (DMSO-d6): 6.98 brs, 2 H an d 6.53 brs,
2 H (NH2); 5.69 s, 1 H (H-5); 3.39 t, 2 H, J(4′,3′) = 6.3 (H-4′); 2.35 t, 2 H, J(1′,2′) = 7.4 (H-1′);
1.56 brpen t, 2 H an d 1.41 brpen t, 2 H (H-2′ an d H-3′). 13C NMR (DMSO-d6): 165.03 (C-4);
162.93 (C-2); 159.94 (C-6); 93.56 (C-5); 60.53 (C-4′); 34.42 (C-1′); 32.07 (C-3′); 24.32 (C-2′).
For C8H14N4O (182.2) calculated: 52.73% C, 7.74% H, 30.75% N; foun d: 52.55% C, 7.82% H,
30.58% N.
2,4-Diam in o-6-{[3-(diisopropoxyph osph oryl)m eth oxy]propyl}pyrim idin e (8) an d
2,4-Diam in o-6-{[3-(diisopropoxyph osph oryl)m eth oxy]prop-1-en -1-yl}pyrim idin e (12)
Method A: 2,4-Diam ino-6-{[3-(diisopropoxyphosphoryl)m ethoxy]p ro p -1-yn -1-yl}p yrim id in e
(3; 0.38 g, 1.1 m m ol, purified by HPLC) was h ydrogen ated at atm osph eric pressure in m eth an ol
(20 m l) over 5% palladium on ch arcoal (0.1 g) at room tem perature un der stirrin g for 2 days.
Th e m ixture was filtered th rough a pad of Celite, th e catalyst was wash ed with h ot m eth a-
n ol an d th e filtrate was evaporated to obtain crude product 8 (0.36 g, 94%), wh ich was di-
Collect. Czech. Chem. Commun. (Vol. 70) (2005)