| 7% |
|
General procedure: [0059] General procedure- method A. N3-ferf-Butyloxycarbonyl-5-bromomethyl-3',5'-0/'s- 0-feri-butyldimethylsilyl-2'-deoxyuridine(5-BrCH2-dU) and appropriate alcohol (4-20eq) were heated neat at 1 10-120C for 1-3hours under argon atmosphere. The mixture was cooled down to room temperature, dissolved in tetrahydrofuran (ca 5 ml), and to this solution chilled at 0 C tetra-n-butylammonium fluoride trihydrate (TBAF) was added (ca 2.5 eq.). The reaction mixture was stirred for 18 hours while gradually warming up to room temperature. The solvent was removed under reduced pressure and the residue was purified by silica gel (chloroform/methanol = 1 :0 to 10:1 ) and then by C8 reverse-phase column chromatography (water/methanol = 19:1 to 1 :4) to yield the product as a waxy solid. [0076] 5-[{(2-nitrophenyl)phenyl}methoxymethyl]-2'-deoxyu dine (KB-1-85). Heating 5- BrCH2-dU (210 mg, 0.385 mmol) with a-phenyl-2-nitrobenzyl alcohol (phenyl(2- nitrophenyl)methanol) (361 mg, 1.576 mmol) for 2.5 hours at 110-1 17C followed by purification of bis- and mono-TBS products with subsequent treatment with TBAF (73 mg, 0.231 mmol) afforded after purification (method A) 12 mg (7%) of product as 1 :1 mixture of diastereomers. 1H NMR (400 MHz, CD3OD) for diastereomers:5 8.04 and 8.00 (2 s, 1 H), 7.88 (m, 1 H), 7.68 (m, 2 H), 7.52 (m, 1 H), 7.34 (m, 5 H), 6.28 (m, 1 H), 6.18 and 6.17 (2 s, 1 H), 4.42 (m, 1 H), 4.30 (m, 3 H), 3.94 (m, 1 H), 3.78 (m, 2 H), 2.28 (m, 2 H). 13C NMR (100 MHz, CD3OD) for diastereomers: delta 163.71 (C), 159.43 (C), 158.87 (C), 150.64 (C), 140.03and 139.74 (CH), 136.21 and 136.18 (C), 132.60 (CH), 128.13 (CH), 128.1 1 (CH), 128.09 (CH), 127.58 (CH), 123.92 (CH), 123.87 (CH), 1 10.71 (C), 87.59 (CH), 85.13 (CH), 78.29 and 78.16 (CH), 70.82 (CH), 64.01 and 63.91 (CH2), 61.48 (CH2), 39.95 (CH2). HRMS (ES+ TOF) for [MNa]+C23H29N308Na calculated: 492.13830, observed: 492.13830. |
| 7% |
|
General procedure: N3-tert-butyloxycarbonyl-5-bromomethyl-3?,5?-bis-O-tert-butyldimethylsilyl-2?-deoxyuridine (1)18 and appropriate alcohol (4-20 equiv) were heated neat at 110-120 C for 0.5-3 h under argon atmosphere. The mixture was cooled down to room temperature, dissolved in ethyl acetate (ca. 5 mL), and silica (0.5-1.0 g) was added. The mixture was evaporated, and the solid was applied onto a silica gel chromatography column (hexane/ethyl acetate=15:1 to 2:1, then dichloromethane/methanol=0:1 to 10:1). Fractions that were not the starting alcohol were collected, evaporated under reduced pressure, dissolved in tetrahydrofuran (ca. 5 mL), and to this solution chilled at 0 C tetra-n-butylammonium fluoride trihydrate (TBAF) was added (2.5 equiv). The reaction mixture was stirred for 2-3 h while gradually warming up to room temperature. The solvent was removed under reduced pressure and the residue was purified by silica gel (ethyl acetate/methanol=1:0 to 20:1) to afford product as waxy solid. 4.1.1.17 5-[{(2-Nitrophenyl)phenyl}methoxymethyl]-2'-deoxyuridine (o-2q) Heating 1 (210 mg, 0.323 mmol) with alpha-phenyl-2-nitrobenzyl alcohol (phenyl(2-nitrophenyl)methanol) (361 mg, 1.576 mmol) for 2.5 h at 110-117 C followed by purification of bis- and mono-TBS products with subsequent treatment with TBAF (73 mg, 0.231 mmol) afforded after purification 12 mg (7%) of product as 1:1 mixture of diastereomers. 1H NMR (400 MHz, CD3OD) for diastereomers: delta 8.04 and 8.00 (2s, 1H), 7.88 (m, 1H), 7.68 (m, 2H), 7.52 (m, 1H), 7.34 (m, 5H), 6.28 (m, 1H), 6.18 and 6.17 (2s, 1H), 4.42 (m, 1H), 4.30 (m, 3H), 3.94 (m, 1H), 3.78 (m, 2H), 2.28 (m, 2H). 13C NMR (100 MHz, CD3OD) for diastereomers delta 163.71 (C), 159.43 (C), 158.87 (C), 150.64 (C), 140.03 and 139.74 (CH), 136.21 and 136.18 (C), 132.60 (CH), 128.13 (CH), 128.11 (CH), 128.09 (CH), 127.58 (CH), 123.92 (CH), 123.87 (CH), 110.71 (C), 87.59 (CH), 85.13 (CH), 78.29 and 78.16 (CH), 70.82 (CH), 64.01 and 63.91 (CH2), 61.48 (CH2), 39.95 (CH2). HRMS (ES+ TOF) for [MNa]+ C23H29N3O8Na calculated: 492.13820, observed: 492.13830. |
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