A New Series of Acyclonucleosides
J . Org. Chem., Vol. 65, No. 20, 2000 6669
organic layer was washed with an aqueous saturated solution
of NaHCO3, dried over MgSO4, and evaporated under reduced
pressure. Flash chromatography (MeOH/ethyl acetate 1/99) of
the residue afforded pyrimidines 3c and 3g as white solids.
1-(2-H yd r oxy-1-p h e n yle t h yl)-1H -p yr im id in e -2,4-d i-
on e (3c): 91% yield, 1H NMR (CDCl3) δ 4.21 (m, 2H), 5.54 (d,
J ) 8 Hz, 1H), 5.85 (m, 1H), 7.15 (d, J ) 8 Hz, 1H), 7.30 (m,
5H). 13C NMR (CDCl3) δ 59.5, 62.0, 102.1, 128.0, 128.7, 129.2,
135.7, 142.9, 152.0, 163.7. HRMS calcd for C12H12O3N2 + H+
m/z 233.0926, obs m/z 233.0920.
pressure. Flash chromatography (MeOH/ethyl acetate 1/99) of
the residue afforded pyrimidines 3k (71 mg, 66% yield) as a
1
white solid. H NMR (CDCl3) δ 1.27 (d, J ) 6.2 Hz, 3H), 3.29
(s,3H), 4.41 (d, 1H), 4.79 (m, 1H), 5.70 (d, J ) 8.2 Hz, 1H),
7.32 (m, 5H), 7.48 (d, J ) 8 Hz, 1H), 9.2 (brs, 1H). 13C NMR
(CDCl3) δ 16.3, 57.7, 60.8, 85.2, 101.9, 127.3, 128.8, 129.0,
137.8, 143.1, 151.4, 163.8. [R]25D: -31 (c 0.32, MeOH).
Gen er a l P r oced u r e for th e Rea ction of P yr im id in on es
2 w ith TMSCl. To a stirred solution of pyrimidinones 2 (0.703
mmol) in THF (8 mL) was added TMSCl (0.178 mL, 1.408
mmol). After 2 h at room temperature, CH2Cl2 was added, and
the organic layer was washed with an aqueous saturated
solution of NaHCO3, dried over MgSO4, and evaporated under
reduced pressure. Flash chromatography (MeOH/ethyl acetate
1/99) of the residue afforded pyrimidines 3a , 3e, 3f, 3i as white
solids
1-((2S)-H yd r oxy-(1S)-m et h yl-2-p h en ylet h yl)-1H -p yr i-
1
m id in e-2,4-d ion e (3g): 78% yield, H NMR (CDCl3) δ 0.9 (d,
J ) 7.2 Hz, 3H), 2.74 (brs,1H), 4.86 (m, 2H), 5.02 (m, 1H),
5.66 (d, J ) 5.0 Hz,1H), 7.33 (m,6H), 8.75 (brs, 1H). 13C NMR
(CDCl3) δ 15.8, 60.9, 78.3, 104.9, 130.0, 131.7, 132.4, 145.7,
147.8, 155.0, 168.0. [R]25D: +13 (c 0.3, MeOH). HRMS calcd
for C13H14O3N2 + H+ m/z 247.1083, obs m/z 247.1078.
1-(2-Ch lor o-1-p h en ylet h yl)-1H -p yr im id in e-2,4-d ion e
Gen er a l P r oced u r e for th e Ba sic Hyd r olysis: P r ep a r a -
tion of P yr im id in e 3j. To a stirred solution of pyrimidinones
2c (100 mg, 0.438 mmol) in a 1:1 mixture of THF and H2O (4
mL) was added NaOH as solid (26 mg, 0.650 mmol). After 1 h
at room temperature, CH2Cl2 was added, and the organic layer
was washed with an aqueous saturated solution of NH4Cl,
dried over MgSO4, and evaporated under reduced pressure.
Flash chromatography (MeOH/ethyl acetate 1/99) of the
residue afforded pyrimidines 3j as white solids (105 mg).
1-((2R)-Hyd r oxy-(1S)-m eth yl-2-p h en yleth yl)-1H-p yr i-
1
(3a ): 80% yield, H NMR (CDCl3) δ 4.10 (m, 2H), 5.63 (d, J )
8.2 Hz,1H), 5.93 (t, J ) 7.2 Hz, 1H), 7.03 (d, J ) 8.2 Hz, 1H),
7.30 (m, 5H). 13C NMR (CDCl3) δ 43.2, 59.1, 102.5, 127.5, 129.2,
129.4, 134.7, 141.7, 151.2, 163.1. Anal. Calcd for C12H11ClO2N2
C, 57.49; H, 4.42; N, 11.17. Found C, 57.20; H, 4.71; N, 10.43.
1-(2-Ch lor o-1-p h en ylet h yl)-6-m et h yl-1H -p yr im id in e-
2,4-d ion e (3e): 78% yield, 1H NMR (CDCl3) δ 2.31 (s, 3H),
4.18 (dd, J ) 5,0, 11.2 Hz, 1H), 4.75 (dd, J ) 8.9, 11.2 Hz,
1H), 5.30 (brs, 1H), 5.55 (s, 1H), 7.29 (m, 5H), 8.8 (brs, 1H).
13C NMR (CDCl3) δ 20.7, 43.0, 61.1, 102.3, 126.0, 127.9, 128.2,
135.3, 150.1, 153.6, 161.9.
1
m id in e-2,4-d ion e (3j): 97% yield, H NMR (CDCl3) δ 0.9 (d,
J ) 7.2 Hz, 3H), 2.74 (brs,1H), 4.86 (m, 2H), 5.66 (d, J ) 5
Hz,1H), 7.33 (m,5H), 8.75 (brs, 1H). 13C NMR (CDCl3) δ 15.8,
60.9, 78.3, 104.9, 130.0, 131.7, 132.4, 145.7, 147.8, 155.0, 168.0.
[R]25D: -25 (c 0.7, CHCl3).
1-((2R)-Ch lor o-(1S)-m eth yl-2-p h en yleth yl)-1H-p yr im i-
1
d in e-2,4-d ion e (3f): 79% yield, H NMR (CDCl3) δ 1.20 (d, J
) 8 Hz, 3H), 5.10 (brs, 1H), 5.20 (m, 1H), 5.65 (d, J ) 7.5 Hz,
1H), 7.07 (d, J ) 7.5 Hz, 1H), 7.28 (m, 5H), 9.0 (brs, 1H). 13C
NMR (CDCl3). δ 16.8, 53.5, 64.6, 102.7, 128.1, 129.4, 129.7,
137.3, 163.4, 166.6. [R]25D: +432 (c 0.48, MeOH). HRMS calcd
for C13H13ClO2N2 + H+ m/z 265.0744, obs m/z 265.0753.
Gen er a l P r oced u r e for th e Acid ic Meth a n olysis: P r ep a -
r a tion of P yr im id in e 3b a n d 3h . To a stirred solution of
pyrimidinones 2a and 2c (0.438 mmol) in MeOH (4 mL) was
added p-toluenesulfonic acid (100 mg, 0.581 mmol). After 12
h at reflux, MeOH was evaporated under reduced pressure,
CH2Cl2 was added, and the organic layer was washed with an
aqueous saturated solution of NaHCO3, dried over MgSO4, and
evaporated under reduced pressure. Flash chromatography
(MeOH/ethyl acetate 1/99) of the residue afforded pyrimidines
3b and 3h as white solids.
1-(2-Me t h oxy-1-p h e n yle t h yl)-1H -p yr im id in e -2,4-d i-
on e (3b): 87.% yield, 1H NMR (CDCl3) δ 3.35 (s, 3H), 3.85 (dd,
J ) 5.2, 10.7 Hz, 1H), 3.96 (dd, J ) 5.2, 10.7 Hz, 1H), 5.56 (d,
J ) 8.1 Hz, 1H), 5.88 (t, J ) 5.2 Hz, 1H), 7.16 (d, J ) 8.1 Hz,
1H), 7.28 (m, 5H), 8.9 (brs, 1H).13C NMR (CDCl3) δ 57.0, 59.2,
71.7 101.7, 127.9, 128.6, 129.1, 136.5, 142.9, 150.5, 163.5.
1-((2S)-Met h oxy-(1S)-m et h yl-2-p h en ylet h yl)-1H -p yr i-
m id in e-2,4-d ion e (3h ): 95% yield, 1H NMR (CDCl3) δ 1.18
(d, J ) 5.0 Hz, 3H), 3.21 (s, 3H), 4.33 (d, J ) 2.5 Hz,1H), 4.72
(m,1H,), 5.62 (d, J ) 7.5 Hz,1H), 7.25 (m, 5H), 7.40 (d, J ) 7.5
Hz,1H), 9.2 (brs, 1H). 13C NMR (CDCl3) δ 12.2, 56.3, 57.9, 84.9,
101.7, 126.9, 128.5, 129.0, 138.1, 142.9, 151.5, 163.8. Anal.
Calcd for C14H16O3N2 C, 64.60; H, 6.20; N, 10.76. Found C,
64.70; H, 6.20; N, 10.59.
1-(2-Ch lor op r op yl)-1H-p yr im id in e-2,4-d ion e (3i): 85%
1
yield, H NMR (CDCl3) δ 1.52 (d, J ) 6.8 Hz, 3H), 3.44 (dd, J
) 9.2, 14.2 Hz, 1H), 4.21 (dd, J ) 3.2, 14.2 Hz, 1H), 4.32 (m,
1H), 5.64 (d, J ) 7.5 Hz, 1H), 7.20 (d, J ) 7.5 Hz, 1H). 13C
NMR (CDCl3) δ 22.7, 55.7, 56.9, 102.2, 145.9, 151.4, 164.2.
1-(2-Azid o-1-p h en yleth yl)-9-m eth yl-1H-p yr im id in e-2,4-
d ion e (3d ). To a stirred solution of pyrimidinones 2a (0.703
mmol) in THF (4 mL) was added TMSN3 (0.123 mL, 0.934
mmol) and TBAF (0.70 mL of a 1 M solution in THF, 0.700
mmol). After 24 h at room temperature, CH2Cl2 was added,
and the organic layer was washed with an aqueous saturated
solution of NaHCO3, dried over MgSO4, and evaporated under
reduced pressure. Flash chromatography (MeOH/ethyl acetate
1/99) of the residue afforded pyrimidines 3d (103 mg, 95%
yield) as white solids: 1H NMR (CDCl3) δ 4.05 (m, 2H), 5.70
(d, J ) 7.5 Hz, 1H), 5.92 (t, J ) 5.0 Hz, 1H), 7.07 (d, J ) 7.5
Hz, 1H), 7.35 (m, 5H), 9.18 (brs, 1H). 13C NMR (CDCl3) δ 52.0,
57.5, 103.1, 128.2, 129.6, 129.8, 135.2, 142.1, 151.5, 163.3.
HRMS calc. For C12H11O2N5 + H+ m/z 258.0991, obs m/z
258.0987.
1-((2R)-Meth oxy-(1S)-m eth yl-2-p h en yleth yl)-1H-p yr i-
m id in e-2,4-d ion e (3k ). To a stirred solution of pyrimidinones
3j (100 mg, 0.438 mmol) in THF (4 mL) were added NaH (32
mg, 0.880 mmol) and methyl iodide (0.038 mL, 0.600 mmol).
After 12 h at room temperature, CH2Cl2 was added, and the
organic layer was washed with an aqueous saturated solution
of NH4Cl, dried over MgSO4, and evaporated under reduced
Su p p or tin g In for m a tion Ava ila ble: Spectrometric in-
formation (1H NMR) for compounds 2a ,b, 3a -d , 3e-k and
13C NMR for compounds 2a -d , 3c-e, 3g-k . This material is
J O000812D