Molecules 2011, 16
5123
6-[3-Hydroxy-2-(4-methoxytriphenylmethoxymethyl)propyl]-1,3-dimethoxymethyl-5-methylpyrimidin-
2,4-dione (11). 1H-NMR: 7.2−7.4 (10H, m, Ph), 7.18 (2H, m, Ph), 6.87 (2H, m, Ph), 5.24 (2H, s, CH2-
N1, 5.20 (1H, m, CH2-N3), 5.18 (1H, m, CH2-N3), 4.77 (1H, t, J = 4.5 Hz, OH), 3.74 (3H, s, OCH3),
3.46 (2H, m, H-3''-OH), 3.24 (3H, s, OCH3), 3.23 (3H, s, OCH3), 2.92 (2H, m, H-3'-OMTr), 2.69 (2H,
m, H-1'), 2.03 (1H, m, H-2'), 1.74 (3H, s, CH3-5). 13C-NMR: 162.59 (C-4), 158.61 (C-Phquat-12'),
152.36 (C-2), 150.46 (C-6), 144.87, 144.68 (C-Phquat-5',5''), 135.49 (C-Phquat-9'), 130.37 (CH-Ph-
10',10''), 128.27−128.48 (CH-Ph-6'-7''), 127.30 (CH-Ph-8',8''), 113.59 (CH-Ph-11',11''), 108.65 (C-5),
86.50 (C-4',4''), 73.71 (CH2-N1), 72.14 (CH2-N3), 64.24, 61.60 (C-3',3''), 57.39 (OCH3-N1), 56.56
(OCH3-N3), 55.49 (OCH3-MTr), 42.03 (C-2'), 27.98 (C-1'), 12.18 (CH3-5). Positive ESI-MS 575
(M+H). Anal. Calcd for C33H38N2O7: C 68.97, H 6.67. Found: C 69.05, H 6.70.
6-[3-Hydroxy-2-(4-methoxytriphenylmethoxymethyl)propyl]-1-methoxymethyl-5-methylpyrimidin-2,4-
dione (12). 1H-NMR: 11.22 (1H, s, NH-3), 7.2−7.4 (10H, m, Ph), 7.20 (2H, m, Ph), 6.87 (2H, m, Ph),
5.34 (2H, s, CH2-N1), 3.84 (1H, m, H-3''-OH), 3.74 (3H, s, OCH3), 3.68 (1H, m, H-3''-OH), 3.22 (3H,
s, OCH3), 3.03 (2H, m, H-3'-OMTr), 2.73 (2H, m, H-1'), 2.18 (1H, m, H-2'), 1.74 (3H, s, CH3-5). 13C-
NMR: 165.08 (C-4), 158.64 (C-Phquat-12'), 150.83 (C-2), 149.20 (C-6), 144.92 (C-Phquat-5',5''), 135.40
(C-Phquat-9'), 130.36 (CH-Ph-10',10''), 128.30−128.36 (CH-Ph-6'-7''), 127.32 (CH-Ph-8',8''), 113.64
(CH-Ph-11',11''), 109.47 (C-5), 86.44 (C-4'), 73.77 (CH2-N1), 68.68 (C-3',3''), 59.52 (OCH3-N1),
55.49 (OCH3-MTr), 44.05 (C-2'), 28.85 (C-1'), 11.17 (CH3-5). Positive ESI-MS 531 (M+H). Anal.
Calcd for C31H34N2O6: C 70.17, H 6.46. Found: C 70.25, H 6.44.
3.2.5. 6-[(3-Fluoro-2-hydroxymethyl)propyl]-1,3-dimethoxymethyl-5-methylpyrimidin-2,4-dione (13),
6-[(3-hydroxy-2-hydroxymethyl)propyl]-1,3-dimethoxymethyl-5-methylpyrimidin-2,4-dione (7) and 4-
hydroxymethyl-8-methoxymethyl-6-methyl-4,5-dihydro-pyrimido[1,6-c][1,3]oxazepine-7,9-dione (14)
A solution of dry 10 (30 mg, 0.037 mmol) in anhydrous CH2Cl2 (8 mL) was cooled to −78 °C and
stirred for 15 min under Ar atmosphere. DAST (0.05 mL) was added dropwise and reaction was kept
at −78 °C for additional 15 min after which cooling bath was removed. After 5 h of stirring at r.t.,
saturated aqueous solution of NaHCO3 (10 mL) was added and reaction was partitioned. Organic layer
was separated, dried over MgSO4 and evaporated to dryness. Raw product was then dissolved in
CH3OH (0.5 mL) and 5% HCl (0.7 mL) and refluxed for 15 min. Solvent was evaporated and residue
was purified by column chromatography (CH2Cl2-CH3OH = 30:1) to afford 13 (1.2 mg, 10.7%), 7
(3.6 mg, 32.2%) and 14 (3.1 mg, 31%).
6-[(3-Fluoro-2-hydroxymethyl)propyl]-1,3-dimethoxymethyl-5-methylpyrimidin-2,4-dione (13). 1H-
NMR: 5.28 (2H, s, CH2-N1), 5.22 (2H, s, CH2-N3), 4.92 (1H, t, J = 4.9 Hz, OH), 4.45 (2H, ddd,
J = 47.6, 4.9, 1.9 Hz, CH2F-3''), 3.45 (2H, m, H-3'-OH), 3.28 (6H, s, OCH3), 2.72 (2H, m, H-1'), 2.10
(1H, m, H-2'), 1.89 (3H, s, CH3-5). 19F-NMR: 225.79 (td, J = 47.9, 24.8 Hz). 13C-NMR: 162.73 (C-4),
152.45 (C-2), 149.63 (C-6), 109.06 (C-5), 83.67 (d, J = 165.29, CH2F-3''), 74.88 (CH2-N1), 72.50
(CH2-N3), 60.05 (d, J = 5.94 Hz, C-3'), 57.42 (OCH3-N1), 56.47 (OCH3-N3), 41.66 (d, J = 17.74 Hz,
C-2'), 26.32 (d, J = 4.96 Hz, C-1'), 12.10 (CH3-5). Positive ESI-MS 305 (M+H). Anal. Calcd for
C13H21FN2O5: C 51.31, H 6.96. Found: C 51.27, H 6.98.