* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
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[1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 24, p. 7184 - 7193
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[ 58-96-8 ]
[ 316-46-1 ]
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[ 65-46-3 ]
[ 316-46-1 ]
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[1] Patent: US4122251, 1978, A,
4
[ 3871-66-7 ]
[ 316-46-1 ]
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[1] Chemistry - A European Journal, 2017, vol. 23, # 16, p. 3910 - 3917
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[ 2560-60-3 ]
[ 316-46-1 ]
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[1] Chemistry - A European Journal, 2017, vol. 23, # 16, p. 3910 - 3917
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8
[ 41028-66-4 ]
[ 316-46-1 ]
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[1] Chemistry - A European Journal, 2017, vol. 23, # 16, p. 3910 - 3917
[2] Chemistry - A European Journal, 2017, vol. 23, # 16, p. 3910 - 3917
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[ 119003-30-4 ]
[ 316-46-1 ]
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[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1988, p. 2547 - 2554
10
[ 119003-30-4 ]
[ 316-46-1 ]
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[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1988, p. 2547 - 2554
11
[ 13035-61-5 ]
[ 316-46-1 ]
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[1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 24, p. 7184 - 7193
12
[ 58-96-8 ]
[ 316-46-1 ]
[ 119068-03-0 ]
[ 119003-30-4 ]
[ 119003-30-4 ]
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[1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1988, p. 2547 - 2554
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1988, p. 2547 - 2554
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[ 464169-57-1 ]
[ 316-46-1 ]
[ 796-66-7 ]
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14
[ 58-96-8 ]
[ 316-46-1 ]
[ 119068-04-1 ]
[ 119003-30-4 ]
[ 119003-30-4 ]
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15
[ 5991-01-5 ]
[ 316-46-1 ]
Reference:
[1] Patent: US2885396, 1957, ,
16
[ 78948-09-1 ]
[ 58-96-8 ]
[ 316-46-1 ]
[ 119068-03-0 ]
[ 119003-30-4 ]
[ 119003-30-4 ]
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17
[ 316-46-1 ]
[ 2341-22-2 ]
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18
[ 55474-11-8 ]
[ 316-46-1 ]
[ 2341-22-2 ]
Reference:
[1] Chemistry of Heterocyclic Compounds, 1982, vol. 18, # 5, p. 533 - 536
REFERENCE EXAMPLE 2 Preparation of 3',5'-O-(tetraisopropyldisiloxane-1,3-diyl)-<strong>[316-46-1]5-<strong>[316-46-1]fluorouridine</strong></strong> (4) In 300 ml of pyridine was dissolved 10 g of <strong>[316-46-1]5-<strong>[316-46-1]fluorouridine</strong></strong> and, under ice-cooling and stirring, 13.2 g of 1,3-dichlorotetraisopropyldisiloxane was added dropwise. After completion of the dropwise addition, the mixture was stirred at room temperature for 6 hours to conduct the reaction, and the solvent was removed under reduced pressure. The resulting residue was dissolved in 220 ml of chloroform, and washed successively with water, 1 N-hydrochloric acid and water. The chloroform layer was dried over anhydrous magensium sulfate, condensed under reduced pressure and the residue obtained was applied to silica gel column chromatography to obtain 12.1 g (Yield: 54%) of the title compound. NMR (CDCl3) delta: 9.87 (1H, bs), 7.91 (1H, d), 5.75 (1H, d), 4.35-4.15 (4H. m), 4.0 (1H, dd), 3.69 (1H, bd), 1.17-0.97 (28H, m).
Isobutyric acid (2R,3R,4R,5R)-2-(5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-5-isobutyryloxymethyl-tetrahydro-furan-3-yl ester[ No CAS ]
With sodium bicarbonate; p-toluenesulfonic acid monohydrate; In acetone;
REFERENCE EXAMPLE 6 Preparation of 2',3'-O-isopropylidene-<strong>[316-46-1]5-<strong>[316-46-1]fluorouridine</strong></strong> (9) In 750 ml of acetone were added 15 g of <strong>[316-46-1]5-<strong>[316-46-1]fluorouridine</strong></strong>, 7.5 ml of 2,2-dimethoxypropane and 1.1 g of p-toluenesulfonic acid monohydrate, and the mixture was reacted at room temperature for 4.5 hours under stirring. After allowed to stand overnight at room temperature, 5 g of sodium hydrogen carbonate was added to the reaction mixture and the mixture was stirred at room temperature for 2.5 hours. After insolubles were filtered off, the filtrate was condensed under reduced pressure, and the obtained crystals were recrystallized from ethanol to give 15.7 g (Yield: 84%) of the title compound as colorless needle crystals.
82%
-Fluorouridine-5'-O-beta-D-Galactopyranoside (M0174) was prepared using a modification of the procedures of Watanabe (Watanabe, K. A., et al., 1981). Under anhydrous conditions, <strong>[316-46-1]fluorouridine</strong> (508 mg, 1.94 mmole) was dissolved in a mixture of anhydrous acetone (15 mL) and 2,2-dimethoxypropane (1.00 mL, 8.13 mmole). To this solution was added para-toluenesulfonic acid, monohydrate (71 mg, 0.37 mmole) and this mixture allowed to stir at room temperature, under an atmosphere of dry nitrogen gas for 18 hours. T.l.c. analysis after this time (SiO2: irrigant=ethylacetate) showed conversion to a higher Rf product (Rf=0.69). Solid sodium bicarbonate (114 mg, 1.35 mmoles) was added to the solution and stirring continued as above for 2 hours. The reaction mixture was filtered, and the white precipitate washed with acetone (5×10 mL). The filtrate was evaporated to a white solid, and dried in vacuo (768 mg, crude). This crude product was recrystallized from hot 95% ethanol. After cooling to 4 C. overnight, colorless needle crystals of the 2,3-isopropylidine derivative were collected by filtration (366 mg, 63%). A second crop of crystals (113 mg) (total yield 479 mg (82%) were also obtained by concentration of the mother liquors and cooling to 4 C. [00145] Under anhydrous conditions, the isopropylidene derivative from above (302 mg, 1.0 mmole, 1st crop) was dissolved in anhydrous dichloromethane (30 mL). To this solution was added dry silver oxide (452 mg, 1.95 mmole), resublimed crystalline iodine (30 mg, 0.12 mmole) and acetobromogalactose (452 mg, 1.1 mmole) with stirring. This reaction mixture was heated to reflux, under anhydrous conditions for 18 hours, cooled, and the reaction mixture filtered through a pad of diatomaceous earth (Celite), and the precipitate washed with chloroform (5×15 mL). The combined filtrates were extracted with water (1×50 mL), 0.1 M sodium thiosulfate solution (1×50 mL) and water (1×50 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and evaporated to dryness (597 mg, 94%). This fully protected nucleoside derivative (M0172) was deblocked in two steps using, first, the procedure of Lichtenhaler, et al. (Lichtenhaler, et al., 1978). The nucleoside derivative (M0172) was added to a solution of trifluoroacetic acid:water (5:1, 24 mL), and allowed to stir at room temperature for 25 minutes. The solution was then evaporated and co-evaporated with dry toluene (4×30 mL) and 1:1 methanol:toluene (1×40 mL), and dried in vacuo to give the crude peracetate derivative (M0173) (471 mg, grey solid). A. sample of this compound (364 mg, 0.54 mmole) was then dissolved in anhydrous methanol (40 mL) under anhydrous conditions (dry nitrogen gas environment) and cooled to 0 C. using an ice-bath. Sodium methoxide solution (25%w/v, 500 muL) was added and this mixture allowed to stir at 0 C. and at room temperature overnight (18 hours). The reaction mixture was neutralized with washed, dry IRC-50(H+) resin (1 gram). The reaction mixture was filtered, and the resin washed with methanol allowing the washes to equilibrate with the resin during each wash (6×30 mL). The combined filtrates were evaporated to a clear oil that was crystallized from methanol:diethylether (1:10, 165 mL) twice. The final crop (201 mg, 87%) was filtered and dried in vacuo to an off-white powder. T.l.c (SiO2, irrigant 1:1 ethylacetate:methanol, Rf=0.50). 1H-n.m.r. (D2O) d: 8.0 (d, 1H, NH), 5.8 (d, 1H, H-1), 4.75 (d, 1H, H-l'), 4.4(d, 1H, H-4'), 4.3-4.1(m, 3H, Gal ring H's), 3.9-3.4 (m, 10H, ring H's).
With TSOH; In methanol; N,N-dimethyl-formamide;
2',3'-O-Isopropylidene-<strong>[316-46-1]5-<strong>[316-46-1]fluorouridine</strong></strong> (65) 2,2-Dimethoxypropane (2 mL) was added to a solution of <strong>[316-46-1]5-<strong>[316-46-1]fluorouridine</strong></strong> (1.05 g, 4 mmol) and TsOH (20 mg) in 5 mL of DMF. After the starting material was consumed as observed by TLC, 20 mL of methanol was added, and the reaction was allowed to stand overnight. Then the solvents were evaporated in vacuo. The resulting solid was recrystallized from hot methanol to give 864 mg of the product as a colorless solid.
Tetradecanoic acid (2R,3R,4R,5R)-2-(5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-5-tetradecanoyloxymethyl-tetrahydro-furan-3-yl ester[ No CAS ]
Hexadecanoic acid (2R,3R,4R,5R)-2-(5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-5-hexadecanoyloxymethyl-4-hydroxy-tetrahydro-furan-3-yl ester[ No CAS ]
With p-toluenesulfonic acid monohydrate; In acetone; for 1.66667h;Heating / reflux;
262 g (1 mol) 5-Fluorouridine and 7.5 g (0.04 mol) p-toluene sulfonic acid monohydrate were stirred and heated to reflux in 2.5 l acetone. After addition of 120 ml dimethoxypropane within 10 minutes reflux was continued for 90 minutes. Subsequently, 2.5 l isohexane were slowly added over a time period of 25-30 minutes to the hot solution, which resulted in crystallization. The suspension was cooled to 0-2 C. and stirred at this temperature for further 60 minutes. The precipitate was isolated by filtration and washed with cold isohexane. The solid was dried in vacuo at 40 C. for 24 hours to give 276 g (91%) product.
<i>N</i>'-[1-(2-dimethylamino-6-hydroxymethyl-tetrahydro-furo[3,4-<i>d</i>][1,3]dioxol-4-yl)-5-fluoro-2-oxo-1,2-dihydro-pyrimidin-4-yl]-<i>N</i>,<i>N</i>-dimethyl-formamidine[ No CAS ]
<i>N</i>'-{1-[2-dimethylamino-6-(4-oxo-4<i>H</i>-benzo[1,3,2]dioxaphosphinin-2-yloxymethyl)-tetrahydro-furo[3,4-<i>d</i>][1,3]dioxol-4-yl]-5-fluoro-2-oxo-1,2-dihydro-pyrimidin-4-yl}-<i>N</i>,<i>N</i>-dimethyl-formamidine[ No CAS ]
<i>N</i>'-{1-[6-(4,6-dihydroxy-4,6-dioxo-4λ5,6λ5-[1,3,5,2,4,6]trioxatriphosphinan-2-yloxymethyl)-2-dimethylamino-tetrahydro-furo[3,4-<i>d</i>][1,3]dioxol-4-yl]-5-fluoro-2-oxo-1,2-dihydro-pyrimidin-4-yl}-<i>N</i>,<i>N</i>-dimethyl-formamidine[ No CAS ]
<i>N</i>'-{1-[6-(4,6-dihydroxy-4,6-dioxo-2-thioxo-2λ5,4λ5,6λ5-[1,3,5,2,4,6]trioxatriphosphinan-2-yloxymethyl)-2-dimethylamino-tetrahydro-furo[3,4-<i>d</i>][1,3]dioxol-4-yl]-5-fluoro-2-oxo-1,2-dihydro-pyrimidin-4-yl}-<i>N</i>,<i>N</i>-dimethyl-formamidine[ No CAS ]
(S)-2-Amino-3-methyl-butyric acid (2R,3S,4R,5R)-5-(5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl ester; compound with toluene-4-sulfonic acid[ No CAS ]
4-(N'-tert-Butoxycarbonyl-hydrazino)-4-oxo-butyric acid (3aR,4R,6R,6aR)-6-(5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester[ No CAS ]
Succinic acid 2,5-dioxo-pyrrolidin-1-yl ester (3aR,4R,6R,6aR)-6-(5-fluoro-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester[ No CAS ]
phosphoric acid mono(3-dodecylmercapto-2-decyloxy)-1-propyl ester[ No CAS ]
[ 316-46-1 ]
[5-fluorouridine-5'-phosphoric acid-(3-dodecylmercapto-2-decyloxy)-propyl ester][ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In pyridine; methanol; water;
EXAMPLE 1 (5-Fluorouridine)-5'-phosphoric acid (3-dodecylmercapto-2-decyloxy)propyl ester 3.6 g (6.1 mmoles) of phosphoric acid (3-dodecylmercapto-2-decyloxy)propyl ester was treated twice with 30 ml of anhydrous pyridine and concentrated by evaporation. The residue was dissolved in 30 ml of anhydrous pyridine, treated with 2.76 g (9.1 mmoles) of 2,4,6-triisopropylbenzenesulfonic acid chloride under nitrogen and stirred at room temperature for 30 minutes. Then, 1.60 g (6.1 mmoles) of <strong>[316-46-1]5-<strong>[316-46-1]fluorouridine</strong></strong> (Fluka) was added, and the charge was allowed to stand under N2 for 24 hours. Hydrolysis was performed using 15 ml of water, the mixture was stirred for another 2 hours at room temperature, freed from solvent under vacuum, and stripped twice using a small amount of toluene. The residue was purified by column chromatography on LiChroprep RP-18 with a linear gradient of methanol/water 7/1 to methanol as the eluant. The yield is 3.1 g (69% of theoretical amount); oil. Rf =0.24 (CH2 Cl2 /MeOH 8/2); Rf =0.55 (CH2 Cl2 /MeoH/H2 O 6.5/2.5/0.4) on Merck 5715 TLC plates, silica gel 60 F. The phosphoric acid (3-dodecylmercapto-2-decyloxy)-propyl ester was prepared as described in WO 92/03462.
N-(Benzyloxycarbonyl)-glycyl-5-fluorouridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
13%
With diisopropyl (E)-azodicarboxylate; triphenylphosphine; In tetrahydrofuran; methanol; N,N-dimethyl-formamide;
Example 4 N-(Benzyloxycarbonyl)-glycyl-<strong>[316-46-1]5-<strong>[316-46-1]fluorouridine</strong></strong> 5-Fluorouridine (0.300 g, 1.144 mmol, Sigma) was suspended in 4.0 mL of anhydrous tetrahydrofuran under nitrogen. Dry DMF (0.25 mL) was added. Slowly, the solid dissolved. Cbz glycine (0.239 g, 1.142 mmol, Aldrich), triphenylphosphine (0.300 g, 1.144 mmol), and DIAD (0.220 g, 1.088 mmol) were added. The yellow solution was stirred for 48 h. The solution was concentrated under reduced pressure and chromatographed eluding successively with 1:20 MeOH:CHCl3, 1:10 MeOH:CHCl3, then 1:5 MeOH:CHCl3 to provide 0.137 g (27%) of the title compound as a colorless oil. (The same reaction without the DMF as a cosolvent resulted in an isolated yield of only 13%): IR (TF) 3300 (br), 1710, 1670 cm-1; 1 H NMR (300 MHz, methanol-d4) delta3.95 (s, 2H, NHCH2 CO), 4.05-4.20 (m, 3H, ribose H-2',3', 4'), 4.35-4.50 (m, 2H, ribose H-5'), 5.09 (s, 2H, benzylic H), 5.81 (m, 1 H, ribose H-1'), 7.25-7.40 (m, 5H, aromatic H), 7.83 (m, 1 H, vinylic H); 13 C NMR (75 MHz, methanol-d4) delta43.41, 64.90, 67.82, 70.65, 74.99, 82.85, 91.43, 125.95 (d, J=34.7 Hz, C 4), 128.77, 128.97, 129.40, 137.86, 141.74 (d, J=234.3 Hz, C5), 150.74, 158.96, 159.24 (d, J=26.2, C4), 171.55; TLC (methanol-chloroform, 1:5) Rf =0.35; exact MS (El) calcd for C19 H20 N3 O9 F: m/z 453.1184. Found: m/z 453.1174.
EXAMPLE 18 The reaction and the treatment were carried out in the same manner as in Example 16 but using cytidine (10 mmol) in place of cytosine to give 5-fluorouridine (1.22 g). Yield, 46.6%. M.P. 183 to 185 C. UV absorption spectrum: lambdamaxpH 2 268 nm; lambdamaxpH 10.0 268 nm. Thin layer chromatography: Rf 0.40. Paper chromatography: Rf 0.37.
2',3',5'-O-tri-n-butyryl-5-fluorouridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70.0%
In tetrahydrofuran; pyridine; water; ethyl acetate;
(a) 5-Fluorouridine (2.0 g, 7.62 mmol) was dissolved in pyridine (60 ml) and thereto was added dropwise a solution of n-butyryl chloride in tetrahydrofuran (2.52 g in 10 ml; 11.8 mmol). After the mixture was stirred at room temperature for 2 hours, the reaction solution was concentrated under reduced pressure. To the residue were added ethyl acetate and water, the mixture was stirred, and the organic layer was separated. After the organic layer was washed with 5 % aqueous HCl solution, saturated NaHCO3 and saturated NaCl, it was dried and concentrated. The obtained residue (3.42 g) was purified by silica gel chromatography (solvent: ethyl acetate/n-hexane) to give 2',3',5'-O-tri-n-butyryl-<strong>[316-46-1]5-<strong>[316-46-1]fluorouridine</strong></strong> as colorless caramel (3.52 g) (yield: 70.0 %). IR(Nujol): numax(cmmin1) 3240, 3100, 1750, 1730, 1710, 1675, 1460, 1380, 1170 FAB-MS (m/z): 473 (MH+)
With polymer-linked p-toluenesulfonic acid; at 20℃; for 1h;
Anhydrous <strong>[316-46-1]5-<strong>[316-46-1]fluorouridine</strong></strong> (1a, 1.0 g, 3.82 mmol, dried for 48 h at 75C over CaCl2 under high vacuum) was suspended in dry acetone (200 ml). To this suspension polymer-linked p-toluene sulfonic acid (15.24 g, 38.1 mmol) was added, and the mixture was stirred at ambient temperature for 1 h. Subsequently, the polymer-bound acid was filtered off, and the filtrate was evaporated to a small volume, whereupon the crude product crystallized. This was filtered and recrystallized from CHCl3/MeOH, 97:3, v/v) to give 1.12 g (97 %) of pure 19a as colourless needles. TLC (silica gel, CHCl3): Rf 0.77. M.p. 196-197 C. 1H-NMR ((D6)DMSO): 11.866 (d, 4J(NH, F) = 5.0, NH); 8.182 (d, 3J(F, H-C(6)) = 7.0, H-C(6)); 5.840 (d, 3J(H-C(1', H-C(2')) = 1.5, H-C(1')); 4.887 (dd, 3J(H-C(2'), H-C(1')) = 2.5, 3J(H-C(2'), H-C(3')) = 6.5, H-C(2')); 4.767 (dd, 3J(H-C(3'), H-C(4')) = 3.5, 3J(H-C(3'), H-C(2')) = 6.5, H-C(3')); 4.114 (psiq, 3J(H-C(4'), H-C(3')) = 3.5, 3J(H-C(4'); H2C(5')) = 4.0, H-C(4')); 3.642 (dd, 3J(Ha-C(5'), H-C(4')) = 4.0, 2J(Ha-C(5'), Hb-C(5')) = -12, Ha-C(5')); 3.588 (dd, 2J(Hb-C(5'), H-C(4')) = 4.5, 3J(Hb-C(5'), Ha-C(5') = -12, Hb-C(5')), 1.493 (s, 3 Hendo-C(alpha')), 1.296 (s, 3Hexo-C(alpha)). 13C-NMR ((D6)DMSO): 157.02 (d, 2J(C(4), F) = 26.2, C(4)); 148.947 (C(2)); 139.898 (d, 1J(C(5), F) = 230.14, C(5)); 125.782 (d, 2J(C(6), F) = 34.6, C(6)); 112.91 (C(acetal)); 90.948 (C(1')); 86.502 (C(4')); 83.740 (C(2')); 80.215 (C(3')); 61.127 (C(5')); 26.982 (Cendo(alpha')); 25.147 (Cexo(alpha)). HR ESI MS: m/z calculated for C12H16FN2O6 (MH+), 303.914; found m/z 305.10.
96%
With sulfuric acid; at 0 - 20℃; for 2h;
To a stirred suspension of <strong>[316-46-1]5-<strong>[316-46-1]fluorouridine</strong></strong> (3.0 g, 11.4 mmol) inanhydrous acetone (120 mL) H2SO4 (1.5 mL) was added dropwiseat 0 C. The reaction mixture was stirred for 2 h at room temperature.The mixture was then neutralized with 6 N NH4OH and evaporatedto afford crude product which was purified by columnchromatography with gradient of MeOH in DCM (5-8%) to yield20,30-O-isopropylidene-<strong>[316-46-1]5-fluoro-uridine</strong> (18) as a white solid(3.30 g, 96%). 1H NMR (500 MHz, MeOD): d 8.18 (1H, d, J = 7.0 Hz,H-6), 5.92 (1H, d, J = 2.5 Hz, H-10), 4.89 (1H, dd, J = 6.5, 2.5 Hz,H-20), 4.87-4.85 (1H, apparent m, H-30), 4.25 (1H, apparent q,J = 3.0Hz H-40) 3.83 (1H, dd, J = 12.0, 3.0Hz, 1 H-50), 3.75 (1H, dd,J = 12.0, 3.0 Hz, 1 H-50), 1.56 (3H, s, CH3), 1.37 (3H, s, CH3). A solutionof 18 (3.30 g, 10.91 mmol) in anhydrous DCM (130 mL) wastreated with imidazole (1.48 g, 21.83 mmol), and TBDMSCl (1.64g, 10.91 mmol) at 0 C. The reaction mixture was allowed to warmto room temperature and was stirred for 3 h. After solvent evaporation,the crude residue was re-dissolved in EtOAc (60 mL),washed with water (30 mL), brine (30 mL), and dried with Na2SO4.Evaporation of the solvent followed by purification by columnchromatography with EtOAc/Hexane (3:7) gave 50-O-(tbutyldimethylsilyl)-20,30-O-isopropylidene-<strong>[316-46-1]5-fluoro-uridine</strong> as afoam (4.08 g, 90%).
An amount of 100mg (0.38mmol) of40was co-evaporated 3 times with 5mL of dry pyridine and dissolved in 3mL of dry pyridine in a 25ml round bottom. Trityl chloride (128mg, 0.46mmol) was added to the reaction mixture. The mixture was heated at 50C for 18h under argon atmosphere. After 18h, the mixture was cooled to room temperature, quenched with 3mL of MeOH and was allowed to stir for 30min. The mixture was evaporated to dryness. The obtained crude compound was purified by column chromatography to obtain 122mg (63%) of41. TLC (MeOH/CH2Cl2, 1:9):Rf=0.80.1H NMR (300MHz, CDCl3):delta7.86 (d, 1H), 7.40-7.37 (m, 6H), 7.31-7.22 (m, 11H), 5.79-5.77 (m, 1H, H-1?), 4.33-4.31 (m, 1H), 4.24-4.21 (m, 1H), 4.14-4.12 (m, 1H), 3.45-2.42 (m, 2H, H-5?/H-5?);13C NMR (75MHz, CDCl3)delta: 149.4, 143.0, 142.0, 138.8, 128.4, 127.8, 127.2, 124.2, 123.7, 89.5, 87.5, 83.6, 74.9, 69.8, 62.6; HRMS (EI+): m/z for [C28H25FN2O6Na]+calcd. 527.1589; found 527.1585.
5-fluoro-1-[(3a'R,4'R,6'R,6a'R)-3a',4',6',6a'-tetrahydro-6'-(hydroxymethyl)spiro[cyclooctane-1,2'-furo[3,4-d][1,3]dioxol]-4'-yl]pyrimidine-2,4(1H,3H)-dione[ No CAS ]