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CAS No. : | 4105-38-8 | MDL No. : | MFCD00023795 |
Formula : | C15H18N2O9 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | AUFUWRKPQLGTGF-FMKGYKFTSA-N |
M.W : | 370.31 | Pubchem ID : | 20058 |
Synonyms : |
2',3',5'-Tri-O-acetyluridine;Tri-O-acetyl uridine;Xuriden;Vistonuridine;Vistogard;Triacetyluridine;RG2133;PN401;2',3',5'-Triacetyluridine
|
Num. heavy atoms : | 26 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.53 |
Num. rotatable bonds : | 8 |
Num. H-bond acceptors : | 9.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 83.48 |
TPSA : | 142.99 Ų |
GI absorption : | Low |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -8.9 cm/s |
Log Po/w (iLOGP) : | 1.45 |
Log Po/w (XLOGP3) : | -0.48 |
Log Po/w (WLOGP) : | -1.46 |
Log Po/w (MLOGP) : | -0.69 |
Log Po/w (SILICOS-IT) : | -0.07 |
Consensus Log Po/w : | -0.25 |
Lipinski : | 1.0 |
Ghose : | None |
Veber : | 1.0 |
Egan : | 1.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.48 |
Solubility : | 12.4 mg/ml ; 0.0334 mol/l |
Class : | Very soluble |
Log S (Ali) : | -2.06 |
Solubility : | 3.26 mg/ml ; 0.00879 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -1.15 |
Solubility : | 26.2 mg/ml ; 0.0708 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 4.42 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With dmap | |
100% | With triethylamine In 1,4-dioxane at 25℃; for 36h; | |
100% | With pyridine at 20℃; for 16h; |
100% | With triethylamine In N,N-dimethyl-formamide at 20℃; | |
99% | With pyridine Cooling with ice; | |
98% | With pyridine at 20℃; Cooling with ice; | General Procedure for Acetylation of 2a, 2b, and 9 to Afford 7, 11, and 10 (Scheme 3and Scheme 4) General procedure: Compound 2a, 2b or 9 (10 mmol) was co-evaporated with pyridine (3 £ 10 mL) to drynessunder reduced pressure. The dry residue was suspended in pyridine (50 mL). Aftercooling of the suspension in an ice bath, acetic anhydride (50 mmol, 4.6 mL for 2a and9; 60 mmol, 5.7 mL for 2b) was added dropwise with vigorous stirring. The ice bath wasremoved and the reaction mixture was well stirred overnight at r.t. After completion ofthe reaction, water (20 mL) was added to quench the acetic anhydride |
96% | With dmap; triethylamine In acetonitrile at 20℃; | |
95% | With pyridine; dmap at 20℃; | |
95% | With dmap In pyridine at 4 - 20℃; for 24h; Inert atmosphere; | |
94% | With pyridine; dmap at 25℃; for 4h; | |
94% | With lithium perchlorate for 10h; Heating; | |
93% | With dmap In acetonitrile for 1h; Ambient temperature; | |
93% | at 100℃; for 1.5h; | |
93% | With dmap; 1-ethylene glycol monomethyl ether-3-methylimidazolium methanesulfonate at 20℃; for 0.416667h; | |
92% | In pyridine at 60℃; for 3h; | |
92% | Stage #1: acetic anhydride With molybdenium(VI) dioxodichloride In dichloromethane at 20℃; for 0.5h; Stage #2: uridine In dichloromethane at 20℃; for 107h; | |
92% | In neat (no solvent) Molecular sieve; Microwave irradiation; Green chemistry; | Optimized MW-assisted peracetylation General procedure: The substrate belonging to one of the subset reported in Table 1(NTC, TC, CP, DGNP) (0.1 mmol) was left to react under MWheating (Synthos 3000, Anton Paar) with dry acetic anhydride(1 mL, 10 mmol) in a 3 mL vial (Rotor 64MG5 ), equipped witha magnetic stirrer in the presence of molecular sieves(10 % w/w). The microwave, equipped with IR sensor forexternal temperature control (IR limit calculated as follows:Tinternal= 1.214 × TIR), has been set with the power programsprovided for its subset as described in Table 1. At the end of thereaction, the mixture was filtered, diluted with ethanol (2 mL)and left under vigorous stirring for 30 minutes at 50 °C. Themixture was then evaporated under reduced pressure and asmall amount of a saturated solution of sodium bicarbonate(3.8 mL, 10 mmol NaHCO3) was added. After the evolution ofCO2, the precipitation of the peracetylated product was observed. The products were separated by simple decantation. Forcompounds which do not precipitate upon addition of NaHCO3,an extraction with AcOEt was needed. The organic phase, afterdrying with Na2SO4, filtration and evaporation, gave the reaction crude. |
90% | With vanadyl triflate In dichloromethane at 20℃; for 96h; | |
89% | With iron(III) sulfate at 20℃; for 7h; | |
88% | With pyridine at 60℃; for 3h; | |
84% | In pyridine at 20℃; Inert atmosphere; | 4.3 5-Chlorouridine (9) Uridine (6) (3.0g, 12.3mmol) was coevaporated with dry pyridine (2×10mL) and dissolved in dry pyridine (20mL). Acetic anhydride (4.1mL, 43.5mmol) was added and the mixture was stirred at room temperature overnight under argon. Work-up afforded the acetylated uridine intermediate 7 (3.81g, 10.3mmol, 84% yield) as a white foam [ESI for C15H18N2O9 (M+): 258.8 (2,3,5-tri-O-acetylribose+H+, 37.5%), 370.7 (M+H+, 13%), 392.9 (M+Na+, 100%)]. |
79% | With pyridine at 60℃; for 3h; | 51 Synthesis of 5-carbanoylmethyl uridine (03601013036): To a solution of uridine 146 (1 .0 g, 4.0 mmol) in 20 mL of pyridine was added 2 m L (2.16 g, 21 .0 mmol) of acetic anhydride. The resulting reaction mixture was heated to 60 °C for 3 h, and the TLC indicated its completion. The reaction mixture was concentrated, and the residue was purified by flash chromatography on a silica gel column using dichloromethane-methanol (80:1 ) as eluent giving 1 .2 g desired product 1 55 in 79% yield. |
79% | With pyridine at 60℃; for 3h; | 51 Synthesis of 2’,3’,5’-tri-O-acetyluridine (155). Synthesis of 2’,3’,5’-tri-O-acetyluridine (155). To a solution of uridine 146 (1.0 g, 4.0 mmol) in20 mL of pyridine was added 2 mL (2.16 g, 21.0 mmol) of acetic an hydride. The resulting reactionmixture was heated to 60 CC for 3 h, and the TLC indicated its completion. The reaction mixture was concentrated, and the residue was purified by flash chromatography on a silica gel column using dichloromethane-methanol (80:1) as eluent giving 1 .2 g desired product 155 in 79% yield. |
79% | With pyridine at 60℃; for 3h; | 44; 51 yn es s o , , - r - -ace y ur ne . o a so u on o ur ne . g, . mmo n mL of pyridine was added 2 mL (2.1 6 g, 21 .0 mmol) of acetic anhydride. The resulting reaction xture was heated to 60 °C for 3 h, and the TLC indicated its completion. The reaction mixture was ncentrated, and the residue was purified by flash chromatography on a silica gel column using hloromethane-methanol (80:1 ) as eluent giving 1 .2 g desired product 155 in 79% yield. |
With sodium acetate | ||
In pyridine | ||
With pyridine at 20℃; for 1h; | ||
With pyridine for 4h; Ambient temperature; | ||
With pyridine | ||
With pyridine at 60℃; | ||
With dmap; triethylamine In acetonitrile at 20℃; for 1h; | ||
In pyridine | ||
In 1,4-dioxane | ||
With pyridine at 0℃; for 5h; | ||
With pyridine for 5h; | ||
1 Example 1: Triacetyl Uridine RG2133 The investigational drug used in the Examples below was RG2133 (2',3',5'-tri-O- acetyluridine). RG2133 was produced under cGMP conditions from uridine via exhaustive acetylation and purified by repeated precipitation after residual acetic anhydride is removed by distillation. The purified drug substance was dried under reduced pressure and sieved to obtain a uniform solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydroxylamine acetate In pyridine for 24h; Ambient temperature; | |
90% | With tetrabutyl ammonium fluoride In tetrahydrofuran; water at 20℃; for 16h; regioselective reaction; | |
80% | With n-butyllithium; 2,2,2-trifluoroethanol In hexane at 20℃; for 0.5h; |
With ammonia |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With trifluoroacetic acid at 25℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 22% 2: 70% | With 3,3-dimethyldioxirane In ethanol; dichloromethane; acetone at 25℃; | |
1: 28% 2: 56% | With oxygen; ozone In dichloromethane at 0℃; for 0.0166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 18% 2: 65% | With 3,3-dimethyldioxirane In ethanol; dichloromethane; acetone at 25℃; | |
1: 18% 2: 65% | With oxygen; ozone In dichloromethane at 0℃; for 0.0166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 3,3-dimethyldioxirane In dichloromethane; acetone at 25℃; | |
69% | With oxygen; ozone In dichloromethane at 0℃; for 0.0166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: 1,2,4-Triazole With triethylamine; trichlorophosphate In acetonitrile at 5 - 20℃; for 1h; Stage #2: Tri-O-acetyluridine In acetonitrile at 20℃; for 2h; | |
77% | With 4-chlorophenylphosphorodichloridate In pyridine for 48h; | |
65% | With 4-chlorophenylphosphorodichloridate In pyridine for 18h; Ambient temperature; |
With triethylamine; trichlorophosphate 1.) MeCN, 60 min, 0 deg C, 2.) MeCN, 16 h, RT; Yield given. Multistep reaction; | ||
Stage #1: 1,2,4-Triazole With phosphoryl oxychloride on N,N-dimethylformamide; triethylamine In acetonitrile for 0.5h; cooling; Stage #2: Tri-O-acetyluridine In acetonitrile for 2h; | ||
With pyridine; 2-chlorophenyl dichlorophosphate | 4.2. General method for the synthesis of compounds 4a-4m General procedure: 2-Chlorophenyl dichlorophosphate (188 mg, 126 ml, 0.77 mmol) was added to a solution of acetyl protected 2'-deoxyuridine (1a), 5- methyl-2'-deoxyuridine (1b) or uridine (1c) (0.5 mmol) and 1,2,4- triazole (200 mg, 3 mmol) in anhydrous pyridine, cooled to 0 °C. The mixture was stirred for 20 h at room temperature, then evaporated. The residue was partitioned between chloroform and 0.5 M sodium bicarbonate, the chloroform layer was washed with water, dried over Na2SO4, evaporated and dissolved in anhydrous dioxane (3 ml). The corresponding 1-alkylamine (1 mmol) was added to a solution, cooled to 0 °C. The mixture was stirred for 20 h at room temperature, then 3 ml of conc. aq. ammonia solution were added and the mixture was stirred for 40 h at room temperature, then evaporated, the compounds were purified on a column of silica gel (2 15 cm) in chloroform or ethyl acetate were isolated by column chromatography in CHCl3 or ethyl acetate eluted with a gradient of ethanol in chloroform (0-15%) or in or ethyl acetate (0-10%), respectively. The target fractions were evaporated in a vacuum to give the expected compounds yields as colorless amorphous mass with the 60-79% yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With dmap; triethylamine In dichloromethane for 1h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With silver trifluoroacetate In acetonitrile at 15 - 20℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With pyridine for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium hydride In tetrahydrofuran for 45h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With potassium carbonate In N,N-dimethyl-formamide; acetone at 50 - 60℃; | |
83% | With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With pyridine for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With pyridine for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With pyridine for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With silver tetrafluoroborate In acetonitrile at 0℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With pyridine for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With ammonium cerium(IV) nitrate; lithium chloride In acetic acid; acetonitrile at 80℃; for 6h; other conditions investigated; | |
89% | With ammonium cerium (IV) nitrate; lithium chloride In acetonitrile at 80℃; for 44h; | 4.3 5-Chlorouridine (9) The obtained compound 7 (3.81 g, 10.3 mmol) was coevaporated with dry acetonitrile (3x20mL), followed by addition of acetonitrile (165 mL), LiCl (515 mg, 12.2 mmol) and dried ceric ammonium nitrate (CAN, 11.3 g, 20.6 mmol). The mixture was stirred at 80°C for 44h, after which it was concentrated and partitioned between ethyl acetate (400 mL) and brine (200mL). The aqueous layer was extracted with ethyl acetate (2x200 mL) and the organic layers were washed with water (300 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica (0-10% acetone/dichloromethane) yielding the peracetylated-5-chlorouridine 8 as a white powder in 89%yield [NMR: 1H (CDCl3, 300MHz): δ = 2.12 (s, 3H, CH3), 2.13 (s, 3H, CH3), 2.21 (s, 3H, CH3),4.33-4.38 (m, 2H, 5’-H), 4.38-4.42 (m, 1H, 3’-H), 5.32 (m, 1H, 4’-H), 5.33 (m, 1H, 2’-H), 6.08-6.09 (d, J = 4.7Hz, 1H, 1’-H), 7.74 (s, 1H, 6-H), 8.25 (s, 1H, 3-NH); MS: ESI + for C15H17ClN2O9 (M): 258.8 (2,3,5-tri-O-acetylribose+H+, 36%), 404.6 (M+H+, 9%), 426.9 (M+Na+, 100%)]. |
88% | With sodium hydrogencarbonate; lithium chloride In acetonitrile Ambient temperature; electrolysis (Pt electrodes, SCE reference, LiClO4 as supporting electrolyte); |
82% | With ammonium cerium (IV) nitrate; lithium chloride In acetic acid; acetonitrile at 80℃; for 8h; | |
32% | With ammonium cerium (IV) nitrate; 1-ethylene glycol monomethyl ether-3-methylimidazolium methanesulfonate; lithium chloride at 80℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; trimethylsilyl trifluoromethanesulfonate In dichloromethane at 40℃; for 2h; | Typical procedure for the bromination of protected nucleosides: DBH (161 mg, 0.56 mmol) and TMSOTf (0.1 mL, 125 mg, 0.56 mmol) were added to a stirred solution of 1a (380 mg, 1.03 mmol) in CH2Cl2 (15 mL). The resulting brownish-orange mixture was stirred at room temperature for 6 h or until TLC showed the absence of starting material and formation of less polar product. The reaction mixture was diluted with CHCl3 (35 mL) and was washed with saturated NaHCO3/H2O (2 × 100 mL) and brine (100 mL). The organic layer was dried (MgSO4) and concentrated in vacuo to yield 2a (433 mg, 94%) as a colorless foam with purity over 98% (1H NMR) with data as reported.14 |
93% | With ammonium cerium (IV) nitrate; 1-ethylene glycol monomethyl ether-3-methylimidazolium methanesulfonate; lithium bromide at 80℃; for 0.5h; | |
91% | With ammonium cerium(IV) nitrate; lithium bromide In acetonitrile at 80℃; for 1.5h; |
91% | With sodium hydrogencarbonate; lithium bromide In acetonitrile Ambient temperature; electrolysis (Pt electrodes, SCE reference, LiClO4 as supporting electrolyte); | |
89% | With bromine; acetic anhydride; acetic acid at 0 - 20℃; | 51 Synthesis of 5-carbanoylmethyl uridine (03601013036): Compound 155 (1 .2 g, 3.0 mmol) was dissolved in 20 m L of acetic acid, and 1 .2 mL (1 .25 g, 1 1 mmol) acetic anhydride was added. The resulting mixture was cooled to 0 °C in an ice bath, and bromine (0.7 g, 4.0 mmol) was added slowly under stirring. The reaction flask was sealed, and the mixture was stirred at room temperature overnight. Ethanol was added slowly, and the mixture was concentrated under reduced pressure to dryness. The residue was co-evaporated with ethanol and purified by flash chromatography on a silica gel column using methylene chloride-methanol (80:1 ) as eluent providing 1 .3 g desired bromo product 1 56 in 89% yield. 1 H NMR (CDCI3) 5 9.10 (br, 1 H), 7.82 (s, 1 H), 6.07 (m, 1 H), 5.26-5.35 (m , 2H), 4.30-4.41 (m , 3H), 2.20 (s, 3H), 2.1 1 (s, 3H), 2.09 (s, 3H) . |
89% | With bromine; acetic anhydride; acetic acid at 0 - 20℃; Sealed tube; | 51 Synthesis of 5-bromo-2’,3’,5’-tri-O-acetyluridine (156). Synthesis of 5-bromo-2’,3’,5’-tri-O-acetyluridine (156). Compound 155 (1 .2 g, 3.0 mmol) was dissolved in 20 mL of acetic acid, and 1 .2 mL (1 .25 g, 11 mmol) acetic anhydride was added. The resulting mixture was cooled to 0 °C in an ice bath, and bromine (0.7 g, 4.0 mmol) was added slowly under stirring. The reaction flask was sealed, and the mixture was stirred at room temperature overnight. Ethanol was added slowly, and the mixture was concentrated under reduced pressure todryness. The residue was co-evaporated with ethanol and purified by flash chromatography on a silica gel column using methylene chloride-methanol (80:1) as eluent providing 1 .3 g desired bromo product 156 in 89% yield. 1H NMR (CDCI3) ö 9.10 (br, 1 H), 7.82 (s, 1 H), 6.07 (m, 1 H), 5.26-5.35 (m, 2H), 4.30-4.41 (m, 3H), 2.20 (s, 3H), 2.11 (s, 3H), 2.09 (s, 3H). |
89% | With bromine; acetic anhydride In acetic acid at 0 - 20℃; Sealed tube; | 44; 51 Synthesis of 5-bromo-2',3',5'-tri-0-acetyluridine (1 56). Synthesis of 5-bromo-2',3',5'-tri-0-acetyluridine (1 56). Compound 155 (1 .2 g, 3.0 mmol) was solved in 20 mL of acetic acid, and 1 .2 mL (1 .25 g, 1 1 mmol) acetic anhydride was added. The ulting mixture was cooled to 0 °C in an ice bath, and bromine (0.7 g, 4.0 mmol) was added slowly der stirring. The reaction flask was sealed, and the mixture was stirred at room temperature ernight. Ethanol was added slowly, and the mixture was concentrated under reduced pressure to ness. The residue was co-evaporated with ethanol and purified by flash chromatography on a ca gel column using methylene chloride-methanol (80: 1 ) as eluent providing 1 .3 g desired bromo duct 156 in 89% yield. 1 H NMR (CDCI3) δ 9.10 (br, 1 H), 7.82 (s, 1 H), 6.07 (m, 1 H), 5.26-5.35 (m, ), 4.30-4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With iodine; silver sulfate In methanol for 0.133333h; Ambient temperature; | |
98% | With ammonium cerium (IV) nitrate; iodine In acetonitrile at 80℃; for 1h; regioselective reaction; | |
97% | With ammonium cerium(IV) nitrate; iodine In acetonitrile at 80℃; for 1h; |
97% | With ammonium cerium (IV) nitrate; iodine In acetonitrile at 80℃; for 1h; | |
96% | With ammonium cerium(IV) nitrate; iodine In acetonitrile at 80℃; for 1h; other conditions and reagents investigated; | |
96% | With pyridine; iodine; bis-[(trifluoroacetoxy)iodo]benzene In dichloromethane for 5h; Ambient temperature; | |
95% | With Iodine monochloride In dichloromethane at 40℃; for 6h; Inert atmosphere; | |
94% | With Iodine monochloride In dichloromethane for 8h; Heating; | |
94% | With Iodine monochloride In dichloromethane for 2.5h; Heating; | |
93% | With iodine In acetonitrile Ambient temperature; electrolysis (Pt electrodes, Ag/Ag+ reference, LiClO4 as supporting electrolyte); | |
93% | With ammonium cerium (IV) nitrate; iodine In acetonitrile at 80℃; for 1h; | General Procedure for Iodination of Pyrimidine Nucleosides 2b, 7, 11, 10 (Scheme 3and Scheme 4). Ceric (IV) ammonium nitrate (CAN) was dried over P2O5 under vacuum at 60C for4 h.Method A (I2, CAN). Protected nucleoside 10, 11or 7 (5 mmol) was suspended inacetonitrile (80 mL); iodine (3 mmol, 0.76 g) and CAN (2.5 mmol, 1.37 g) were added to the suspension. The reaction mixture was stirred at 80C for 1 h (monitored by TLC,CH2Cl2: acetone, 4:1). After cooling to ambient temperature, the reaction mixture wasevaporated under reduced pressure. The residue was partitioned between a cold mixtureof EtOAc (200 mL), sat. aq. NaCl (100 mL), and 5% NaHSO3 (w/v, 50 mL). The aqueouslayer was washed with EtOAc (2 £ 100 mL). The combined organic layers werewashed with cold 5% NaHSO3 (w/v, 50 mL), sat. aq. NaCl (150 mL), and water (2 £150 mL), dried over Na2SO4, filtered and evaporated. The crude product was purified bysilica gel column chromatography using CH2Cl2: acetone (6:1). The yield of 20,30,50-tri-O-acetyl-5-iodouridine 8 from 7 was 93% (4.65 mmol, 2.31 g). TLC Rf 0.7 (CH2Cl2: acetone,4:1). NMR data were in agreement with those reported previously.27 1H NMR(500 MHz, CDCl3) d 9.09 (s, 1H, NH), 7.88 (s, 1H, H6), 6.08-6.05 (m, 1H, H10), 5.34-5.30 (m, 2H, H20, H3 0 ), 4.42-4.31 (m, 3H, H40, H5 0 ), 2.23 (s, 3H, CH3), 2.12 (s, 3H, CH3),2.09 (s, 3H, CH3). 13C NMR (125 MHz, CDCl3) d 170.19, 169.73, 169.72, 159.57,149.99, 143.87, 87.36, 80.49, 73.23, 70.35, 69.70, 63.15, 21.21, 20.61, 20.51. |
92% | With Iodine monochloride In dichloromethane for 8h; Heating; | |
92% | With ammonium cerium (IV) nitrate; 1-ethylene glycol monomethyl ether-3-methylimidazolium methanesulfonate; lithium iodide at 80℃; for 0.333333h; | |
With ammonium cerium(IV) nitrate; iodine In acetonitrile Heating; | ||
With ammonium cerium (IV) nitrate; iodine In acetonitrile | ||
With ammonium cerium (IV) nitrate; iodine In acetonitrile at 80℃; | ||
With ammonium cerium (IV) nitrate; iodine In acetonitrile at 50℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With immobilized Pseudomonas fluorescens lipase In acetonitrile at 20℃; for 19h; aq. phosphate buffer; Enzymatic reaction; regioselective reaction; | |
92% | With protease subtilisin In water; N,N-dimethyl-formamide at 32℃; for 16h; phosphate buffer, pH = 7; var. enzymes; var. solv.: aq. dioxane, or only water; | |
89% | In methanol at 30℃; for 24h; |
69% | With iodine In methanol at 68℃; for 14.5h; | |
With Candida antarctica B lipase In ethanol | ||
With [tBu2SnClOH]2 In methanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With 3,3-dimethyldioxirane In dichloromethane at 25℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; N,N-dimethyl-formamide In chloroform for 6.5h; Heating; | ||
870 mg | With thionyl chloride; N,N-dimethyl-formamide In chloroform at 100℃; for 2h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With diphenyl hydrogen phosphate; p-toluenesulfonyl chloride In pyridine at 20℃; for 36h; | |
95% | With pyridine; diphenyl hydrogen phosphate; p-toluenesulfonyl chloride at 20℃; for 36h; | |
88% | With diphenyl hydrogen phosphate; p-toluenesulfonyl chloride In pyridine for 36h; Ambient temperature; |
88% | With diphenyl hydrogen phosphate; p-toluenesulfonyl chloride In pyridine for 36h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With diphenyl hydrogen phosphate; p-toluenesulfonyl chloride In pyridine for 36h; Ambient temperature; | |
94% | With diphenyl hydrogen phosphate; p-toluenesulfonyl chloride In pyridine for 36h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.7% | With 4 A molecular sieve; fluorine In ethanol; chloroform; trichlorofluoromethane at -78℃; for 5h; | |
4.8% | With EtN-3HF, platinum wire electrode In acetonitrile for 5.5h; Ambient temperature; electrochemical reaction; | |
4.6% | With triethylamine tris(hydrogen fluoride) In acetonitrile for 5.5h; electrolysis; |
Multi-step reaction with 2 steps 1: 85 percent / 1-(chloromethyl)-4-fluoro-1,4-diazabicyclo<2.2.2>octane bis(tetrafluoroborate)-SELECTFLUOR reagent / acetonitrile / 3 h / Heating 2: 85 percent / pyridine / 2 h / 80 °C | ||
Multi-step reaction with 2 steps 1: 82 percent / 1-(chloromethyl)-4-fluoro-1,4-diazabicyclo<2.2.2>octane bis(tetrafluoroborate)-SELECTFLUOR reagent / acetonitrile / 3 h / Heating 2: 82 percent / pyridine / 2 h / 80 °C | ||
Multi-step reaction with 2 steps 1: 80 percent / aq. 1-(chloromethyl)-4-fluoro-1,4-diazabicyclo<2.2.2>octane bis(tetrafluoroborate)-SELECTFLUOR reagent / acetonitrile / 3 h / Heating 2: 80 percent / pyridine / 2 h / 80 °C | ||
Multi-step reaction with 2 steps 1.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 1.2: 1 h / 80 °C / Microwave irradiation; Sealed tube 2.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 2.2: 2 h / 80 °C / Microwave irradiation; Sealed tube | ||
Multi-step reaction with 2 steps 1.1: nitrosonium tetrafluoroborate / acetonitrile; N,N-dimethyl-formamide / 20 °C 2.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 2.2: 2 h / 80 °C / Microwave irradiation; Sealed tube | ||
Multi-step reaction with 3 steps 1.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 1.2: 1 h / 80 °C / Microwave irradiation; Sealed tube 2.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 2.2: 1 h / 80 °C / Microwave irradiation; Sealed tube 3.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 3.2: 2 h / 80 °C / Microwave irradiation; Sealed tube |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With tetrabutylammonium nitrate In dichloromethane at 0℃; Inert atmosphere; | |
96% | With trifluoroacetyl nitrate In dichloromethane at 0℃; | |
96% | With ammonium nitrate; trifluoroacetic anhydride In dichloromethane at 0℃; |
With ammonium nitrate; trifluoroacetic anhydride In dichloromethane at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With ammonium cerium(IV) nitrate In acetonitrile at 25℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With sodium azide; trichlorophosphate In acetonitrile for 10h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With silver carbonate In toluene at 50℃; for 40h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With Selectfluor In acetonitrile for 3h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With Selectfluor In acetonitrile for 3h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With Selectfluor In acetonitrile for 3h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium carbonate In acetone at 20℃; for 16h; | |
89.5% | With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 3h; | |
With potassium carbonate In N,N-dimethyl-formamide Yield given; |
With potassium carbonate In acetone at 20℃; for 16h; | (2R,3R,4R,5R)-2-(Acetoxymethyl)-5-(3-(buta-2,3-dienyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3,4-diyl diacetate (9) Propargyl bromide (1.1 ml, 10 mmol), (1.85 g, 5 mmol) and anhydrous potassium carbonate (1.38 g, 10 mmol) were stirredat 20°C in acetone for 16 h. The mixture was reduced in vacuo to afford the crude product and used in the next step without further purification. This material (2.04 g, 5 mmol), paraformaldehyde (0.37 g, 12.5 mmol), copper (I) bromide (0.36 g, 2.5 mmol) and diisopropylamine (1.4 ml, 10 mmol) in 1,4-dioxane (8 ml), by stirring and heating at reflux for 16 h. Purification by flash chromatography eluting with 1:2 v/v hexane-EtOAc (Rf 0.3) afforded the product as a pale yellow gum (1 g, 50%). dH (300 MHz, CDCl3) 7.39(d, 1H, J 8.1, aryl CH), 5.99 (d, 1H, J 4.5, alkyl CH), 5.82 (d, 1H, J 8.1,aryl CH), 5.38 (dd, 1H, J 5.8, 4.5, alkyl CH), 5.36e5.31 (m, 1H, alkylCH), 5.25 (tt, 1H, J 12.8, 6.3, allyl CH), 4.83e4.78 (m, 2H, alkyl CH2),4.57e4.49 (m, 2H, allyl CH2), 4.36 (br s, 3H, alkyl CH2 and CH), 2.14, 2.12 and 2.11 (3 s, 3H, alkyl CH); dC 209.0, 170.5, 169.9, 169.8, 162.1, 150.7, 138.1, 102.8, 89.21, 86.0, 79.9, 77.5, 73.2, 70.2, 63.2, 39.4, 21.0, 20.8, 20.7; nmax (film) 2107, 1960, 1749, 1668, 1455, 1372, 1228 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With trifluorormethanesulfonic acid In dichloromethane at 25℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With 1-nitro-1H-pyrazole; trifluorormethanesulfonic acid In acetonitrile for 28h; Ambient temperature; | |
85% | With nitrosonium tetrafluoroborate In N,N-dimethyl-formamide; acetonitrile at 20℃; | |
Multi-step reaction with 2 steps 1.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 1.2: 1 h / 80 °C / Microwave irradiation; Sealed tube 2.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 2.2: 1 h / 80 °C / Microwave irradiation; Sealed tube |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium iodide In acetone at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tributylphosphine; 1,1'-azodicarbonyl-dipiperidine In benzene at 20℃; for 10h; | |
With tributylphosphine; 1,1'-azodicarbonyl-dipiperidine at 20℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tributylphosphine; 1,1'-azodicarbonyl-dipiperidine In benzene at 20℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 50℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water In 1,2-dimethoxyethane at 125℃; for 9h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With 2,4-bis(4-(5,5,6,6,7,7,8,8,9,9,10,10,10-tridecafluorodecyloxy)phenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide In tetrahydrofuran at 55℃; for 17h; | |
54% | With Lawessons reagent In benzene for 24h; Reflux; | |
Multi-step reaction with 2 steps 1.1: phosphoryl oxychloride; triethylamine / acetonitrile / 0.5 h / cooling 1.2: acetonitrile / 2 h 2.1: 62 percent / sodium hydrogen sulfide / dimethylformamide / 3 h / 20 °C |
Multi-step reaction with 2 steps 1: 77 percent / p-ClPhOPOCl2 / pyridine / 48 h 2: 85 percent / NaSH / acetone; H2O / 0.25 h | ||
With tetraphosphorus decasulfide In 1,4-dioxane at 106℃; for 1.5h; | ||
With Lawessons reagent; methanol at 100℃; for 2h; | 2.1; 2.2 Example 1 Dissolve 14 g of compound 3 in 300 mL of toluene, and heat the oil bath to 100° C. and stir until the system is dissolved. Then 16.8 g of Lawson's reagent was added to the reaction, and the reaction was continued at 100°C for 2 hours. After the reaction solution is naturally cooled to room temperature, it is filtered, and the filtrate is directly concentrated under reduced pressure to obtain a crude product. The crude product is separated by the first column chromatography to obtain compound 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With bis-[(trifluoroacetoxy)iodo]benzene In acetonitrile at 25℃; for 0.2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: I2; ceriim(IV) ammonium nitrate / acetonitrile / Heating 2: CuI; Et3N / PdCl2(PPh3)2 / dimethylformamide / 20 °C | ||
Multi-step reaction with 2 steps 1: iodine; ammonium cerium (IV) nitrate / acetonitrile / 80 °C 2: triethylamine; copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride / N,N-dimethyl-formamide | ||
Multi-step reaction with 2 steps 1: Iodine monochloride / dichloromethane / 6 h / 40 °C / Inert atmosphere 2: triethylamine; copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride / acetonitrile / 5 h / 20 °C / Inert atmosphere |
Multi-step reaction with 2 steps 1: ammonium cerium (IV) nitrate; iodine / acetonitrile / 16 h / 50 °C 2: triethylamine; copper(l) iodide; tetrakis(triphenylphosphine) palladium(0) / dichloromethane / 2 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: I2; ceriim(IV) ammonium nitrate / acetonitrile / Heating 2: CuI; Et3N / PdCl2(PPh3)2 / dimethylformamide / 20 °C 3: tetra-n-butylammonium fluoride monohydrate / acetonitrile / 20 °C | ||
Multi-step reaction with 3 steps 1: iodine; ammonium cerium (IV) nitrate / acetonitrile / 80 °C 2: triethylamine; copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride / N,N-dimethyl-formamide 3: tetrabutyl ammonium fluoride / acetonitrile | ||
Multi-step reaction with 3 steps 1: Iodine monochloride / dichloromethane / 6 h / 40 °C / Inert atmosphere 2: triethylamine; copper(l) iodide; bis-triphenylphosphine-palladium(II) chloride / acetonitrile / 5 h / 20 °C / Inert atmosphere 3: potassium fluoride; tetrabutylammomium bromide / acetonitrile / 12 h / 20 °C |
Multi-step reaction with 2 steps 1.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 1.2: 1 h / 80 °C / Microwave irradiation; Sealed tube 2.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 2.2: 2 h / 80 °C / Microwave irradiation; Sealed tube | ||
Multi-step reaction with 2 steps 1.1: nitrosonium tetrafluoroborate / acetonitrile; N,N-dimethyl-formamide / 20 °C 2.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 2.2: 2 h / 80 °C / Microwave irradiation; Sealed tube | ||
Multi-step reaction with 3 steps 1.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 1.2: 1 h / 80 °C / Microwave irradiation; Sealed tube 2.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 2.2: 1 h / 80 °C / Microwave irradiation; Sealed tube 3.1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 1 h / 20 °C / Microwave irradiation 3.2: 2 h / 80 °C / Microwave irradiation; Sealed tube |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With methanol; water; triethylamine at 71℃; Microwave irradiation; | |
Multi-step reaction with 3 steps 1: triethylamine / tetrahydrofuran / 17 h / Ambient temperature 2: 78 percent / conc. NH4OH / methanol 3: 95 percent / triphenylmethyl fluoroborate / acetonitrile; H2O / 1 h / Ambient temperature | ||
With keratinase from Doratomyces microsporus Hydrolysis; Enzymatic reaction; |
With ammonia In methanol at 20℃; | 1 4.4. Preparation of uridines 6a-e General procedure: A mixture of commercially available β-d-ribose tetraacetate (6.28 mmol) with pyrimidine base (8.8 mmol), 30.8 mL of acetonitrile, hexamethyldisilazane (10.9 mmol, 1.24 equiv), saccharine (0.4 mmol, 0.046 equiv) and trimethylsilyl trifluoromethane-sulfonate (8.8 mmol, 1.4 equiv) was taken in a Erlenmeyer flask. The Erlenmeyer flask was placed in a microwave oven and irradiated under at low power (100 W) for 3 min. The reaction mixture was cooled at room temperature, neutralized with aqueous sodium bicarbonate, and extracted with CH2Cl2. The organic extract was dried over anhydrous sodium sulfate, filtered and evaporated to dryness. The residue was purified by column chromatography eluting with AcOEt/hexane 7:3, resulting in the desired nucleosides 5a-e, in 75-82% yields. Finally, the protected nucleosides 5a-e (1 mmol) were treated with ammonia/MeOH (saturated at 0 °C, 41.8 mL) overnight at room temperature. The solvent was evaporated under reduced pressure to give compounds 6a-e, in 85-92% yields. Chemical and physical properties of the ribofuranosyl nucleosides were in agreement with previous data.31-35 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With caesium carbonate In dimethyl sulfoxide for 24h; Inert atmosphere; Irradiation; | 15 Example 15 To a 25 mL reaction tube, Cs2CO3 (0.8 mmol) was added.Compound A-7 (0.4 mmol, 1 eq.),After replacing argon three times, add 3 mL of dimethyl sulfoxide (DMSO).100 μL (1.20 mmol) of Compound B in DMSO was injected.After stirring for 24 hours under blue light irradiation, Compound C-7 was obtained in a yield of 41%. |
40% | With ferrocene; sulfuric acid; dihydrogen peroxide In water; dimethyl sulfoxide at 60 - 70℃; for 0.333333h; | 22 EXAMPLE 22 0.37 g (1.0 mmol) of 2',3',5'-tri-O-acetyluridine and 0.058 g (0.3 mmol) of ferrocene were weighed and placed in a 50 ml two-neck flask equipped with a magnetic rotor and the atmosphere in the flask was replaced with argon. The following materials were added thereinto: 1.8 ml of dimethyl sulfoxide, 2.0 ml of a 1N dimethyl sulfoxide solution of sulfuric acid, 1.0 ml of a 2.1 mol/l dimethyl sulfoxide solution of trifluoromethyl iodide and 0.2 ml of a 30% hydrogen peroxide aqueous solution. The mixture was stirred at 60 to 70°C for 20 minutes and then the resulting solution was cooled to room temperature. Formation of 5-trifluoromethyl-2',3',5'-tri-O-acetyluridine (19F-NMR yield: 45%) was confirmed by 19F-NMR with 2,2,2-trifluoroethanol as an internal standard. 5-Trifluoromethyl-2',3',5'-tri-O-acetyluridine was obtained as a white solid (0.17 g, yield: 40%) by column chromatography. 1H-NMR (deuterated chloroform): δ2.11 (s, 3H), 2.13 (s, 3H), 2.14(s, 3H), 4.34(d, J=13.6Hz, 1H), 4.43(m, 1H), 4.43(dd, J=3.2Hz, 13.6Hz, 1H), 5.34(t, J=5.4Hz, 1H), 5.37(t, J=5.4Hz, 1H), 6.07(d, J=5.4Hz, 1H), 8.01(s, 1H), 9.48(s, 1H). 13C-NMR (deuterated chloroform): δ20.3, 20.4, 62.7, 69.9, 73.2, 80.5, 87.7, 106.2 (q, JCF=33.3Hz), 121.6(q, JCF=270.3Hz), 140.2 (q, JCF=6.0Hz), 149.3, 158.0, 169.6, 169.7, 170.2. 19F-NMR (deuterated chloroform): δ-64.0. |
40% | With caesium carbonate In dimethyl sulfoxide at 20℃; for 24h; Schlenk technique; Inert atmosphere; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | Stage #1: uracil With N,O-bis-(trimethylsilyl)-acetamide In acetonitrile at 20℃; for 0.5h; Stage #2: 2,3,5-tri-O-acetyl-D-ribofuranosyl 1-(N-phenyl)-2,2,2-trifluoroacetimidate With trimethylsilyl trifluoromethanesulfonate In 1,2-dichloro-ethane at 20℃; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 58% 2: 21% 3: 4% 4: 1% | With trifluoroacetic acid In acetonitrile at 60℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: 2,3,5-tri-O-acetyl-β-D-ribofuranosyl ortho-hexynylbenzoate; uracil With N,O-Bis(trimethylsilyl)trifluoroacetamide In acetonitrile at 20℃; for 0.5h; Inert atmosphere; Stage #2: With [bis(trifluoromethanesulfonyl)imidate](triphenylphosphine)gold(I) In acetonitrile at 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trimethylsilyl trifluoromethanesulfonate; 1,1,1,3,3,3-hexamethyl-disilazane; saccharin In acetonitrile Microwave irradiation; | 4.4. Preparation of uridines 6a-e General procedure: A mixture of commercially available β-d-ribose tetraacetate (6.28 mmol) with pyrimidine base (8.8 mmol), 30.8 mL of acetonitrile, hexamethyldisilazane (10.9 mmol, 1.24 equiv), saccharine (0.4 mmol, 0.046 equiv) and trimethylsilyl trifluoromethane-sulfonate (8.8 mmol, 1.4 equiv) was taken in a Erlenmeyer flask. The Erlenmeyer flask was placed in a microwave oven and irradiated under at low power (100 W) for 3 min. The reaction mixture was cooled at room temperature, neutralized with aqueous sodium bicarbonate, and extracted with CH2Cl2. The organic extract was dried over anhydrous sodium sulfate, filtered and evaporated to dryness. The residue was purified by column chromatography eluting with AcOEt/hexane 7:3, resulting in the desired nucleosides 5a-e, in 75-82% yields. Finally, the protected nucleosides 5a-e (1 mmol) were treated with ammonia/MeOH (saturated at 0 °C, 41.8 mL) overnight at room temperature. The solvent was evaporated under reduced pressure to give compounds 6a-e, in 85-92% yields. Chemical and physical properties of the ribofuranosyl nucleosides were in agreement with previous data.31-35 | |
Stage #1: uracil; 1,2,3,5-tetraacetylribose With N,O-bis-(trimethylsilyl)-acetamide In acetonitrile at 90℃; for 2h; Inert atmosphere; Stage #2: With trimethylsilyl trifluoromethanesulfonate In acetonitrile for 16h; Reflux; | 1.1; 1.2 Example 1 25g of uracil 1, 26.4g of (2R,3S,4S,5S)-5-(acetoxymethyl)tetrahydrofuran-2,3,4-triacetic acid triester 2, 48g of N,O- Bis(trimethylsilyl)acetamide was dissolved in 380 mL of acetonitrile, and the reaction was carried out under the protection of argon. The oil bath was heated to 90 and heated to reflux for 2h, and 26 g of trimethylsilyl trifluoromethanesulfonate was added, and continued Heat to reflux for 16h. After the reaction solution was naturally cooled to room temperature, 200 mL of saturated sodium bicarbonate solution and 500 mL of ethyl acetate were added, filtered, and the filtrate was separated into the aqueous phase. The organic phase was washed twice with water and once with saturated brine, using anhydrous sodium sulfate After drying and filtering, the organic phase was concentrated under reduced pressure to obtain compound 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.8% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20 - 50℃; for 3.5h; | 3.1 Step It Synthesis of compound 51 Step It Synthesis of compound 51 [0163] To a solution of compound 42 (1 .061 g, 1.87 mmol), Y03 (930 mg, 5.73 mmol) and Ρ1¾ (1.501 g, 5.73 mmol) in 25 niL THE was added dropwise a solution of DIAD (1.159 g, 5.73 mmol) in 5 rnL THF over 30 min, the resulting mixture was stirred at 50°C for 3h. After the reaction was finished, THF was removed to give the crude product. The crude product was purified on column (eluted with EA) to give 1.37 g compound 51 as an oil, yield: 88.8%. |
88.8% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 50℃; for 3.5h; | 3.1 Step 1: Synthesis of compound 51 [0254] To a solution of compound 46 (1.061 g, 1.87 mmol), Y03 (930 mg, 5.73 mmol) andPPh3 (1.501 g, 5.73 mmol) in 25 mL THF was added dropwise a solution ofDIAD (1.159 g,5.73 mmol) in 5 mL THF over 30 min, the resulting mixture was stirred at 50°C for 3h. Afterthe reaction was finished, THF was removed to give the crude product. The crude productwas purified on column (eluted with EA) to give 1.37 g compound 51 as an oil, yield: 88.8%. |
88.8% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 50℃; for 3.5h; | 3.1 Step 1: Synthesis of Compound 51 To a solution of compound 46 (1.061 g, 1.87 mmol), Y03 (930 mg, 5.73 mmol) and PPh3 (1.501 g, 5.73 mmol) in 25 mL THF was added dropwise a solution of DIAD (1.159 g, 5.73 mmol) in 5 mL THF over 30 min, the resulting mixture was stirred at 50° C. for 3 h. After the reaction was finished, THF was removed to give the crude product. The crude product was purified on column (eluted with EA) to give 1.37 g compound 51 as an oil, yield: 88.8%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 1h; | 1.1 Step 1: Synthesis of compound 47 Step 1: Synthesis of compound 47 [0153] To a solution of compound 42 (3.0 g, 8.1 1 mmol) in DMF (90 mL) was added Y01 (3.0 g, 16.22 mmol) and 2CO3 (4.47 g, 16.22 mmol), the resulting mixture was stirred at 70 °C for Ih. After cooling down, the mixture was diluted with 250 mL water, extracted with ethyl acetate (EA) (250 mLx3), the organic layer was dried over anhydrous Na2S04, concentrated to give a crude product. The crude product was purified on column (eluted with PE / EA - 3: 1) to give 3.61 g 47 as a colorless oil, yield: 94%. .H NMR (300 MHz, CDCI3) δ 7.36 (d, J = 8.1 Hz, IH), 7.32 - 7.27 (m, 4H), 7.25 - 7.18 (m, IH), 5.98 (d, J = 4.0 Hz, IH), 5.81 (d, J= 8.1 Hz, IH), 5.34 (d, J = 2.4 Hz, 2H), 4.35 (s, 3H), 4.13 (m, 2H), 3.01 - 2.84 (m, 2H), 2.14 (dd, J = 12.1 , 4.2 Hz, 9H), 1.26 (t, J = 7.1 Hz, IH). |
94% | With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 1h; | 1.1 Step 1: Synthesis of compound 47 [0248] To a solution of compound 46 (3.0 g, 8.11 mmol) in DMF (90 mL) was added Y01(3.0 g, 16.22 mmol) and K2C03 (4.47 g, 16.22 mmol), the resulting mixture was stirred at 70oc for 1h. After cooling down, the mixture was diluted with 250 mL water, extracted withethyl acetate (EA) (250 mLx3), the organic layer was dried over anhydrous Na2S04,concentrated to give a crude product. The crude product was purified on column (eluted with PE I EA = 3:1) to give 3.61 g 47 as a colorless oil, yield: 94%. 1H NMR (300 MHz, CDCh) 87.36 (d, J= 8.1 Hz, 1H), 7.32-7.27 (m, 4H), 7.25-7.18 (m, 1H), 5.98 (d, J= 4.0 Hz, 1H),5.81 (d, J= 8.1 Hz, 1H), 5.34 (d, J= 2.4 Hz, 2H), 4.35 (s, 3H), 4.13 (m, 2H), 3.01-2.84 (m,2H), 2.14 (dd, J = 12.1, 4.2 Hz, 9H), 1.26 (t, J = 7.1 Hz, 1H). |
94% | With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 1h; | 1.1 Step 1: Synthesis of Compound 47 To a solution of compound 46 (3.0 g, 8.11 mmol) in DMF (90 mL) was added Y01 (3.0 g, 16.22 mmol) and K2CO3 (4.47 g, 16.22 mmol), the resulting mixture was stirred at 70° C. for 1 h. After cooling down, the mixture was diluted with 250 mL water, extracted with ethyl acetate (EA) (250 mL×3), the organic layer was dried over anhydrous Na2SO4, concentrated to give a crude product. The crude product was purified on column (eluted with PE/EA=3:1) to give 3.61 g 47 as a colorless oil, yield: 94%. 1H NMR (300 MHz, CDCl3) δ 7.36 (d, J=8.1 Hz, 1H), 7.32-7.27 (m, 4H), 7.25-7.18 (m, 1H), 5.98 (d, J=4.0 Hz, 1H), 5.81 (d, J=8.1 Hz, 1H), 5.34 (d, J=2.4 Hz, 2H), 4.35 (s, 3H), 4.13 (m, 2H), 3.01-2.84 (m, 2H), 2.14 (dd, J=12.1, 4.2 Hz, 9H), 1.26 (t, J=7.1 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With manganese(III) triacetate dihydrate In acetic acid at 80℃; for 2h; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: (2R,5S)-2-(acetoxymethyl)-5-(p-tolylthio)tetrahydrofuran-3,4-diyl diacetate With trifluoromethylsulfonic anhydride; di(p-tolyl) sulfoxide In dichloromethane at -70 - -40℃; for 0.833333h; Molecular sieve; Stage #2: O,O'-bis-(trimethylsilyl)uracil In dichloromethane; acetonitrile at -70 - -20℃; for 4h; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With acetic anhydride In pyridine | 51 Example 51. To a solution of uridine 146 (1.0 g, 4.0 mmol) in 20 mL of pyridine was added 2 mL (2.16 g, 21.0 mmol) of acetic anhydride. The resulting reaction mixture was heated to 60 °C for 3 h, and the TLC indicated its completion. The reaction mixture was concentrated, and the residue was purified by flash chromatography on a silica gel column using dichloromethane-methanol (80:1) as eluent giving 1.2 g desired product 155 in 79% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With bromine; acetic anhydride In ethanol; acetic acid | 51 Example 51. Compound 155 (1.2 g, 3.0 mmol) was dissolved in 20 mL of acetic acid, and 1.2 mL (1.25 g, 11 mmol) acetic anhydride was added. The resulting mixture was cooled to 0 °C in an ice bath, and bromine (0.7 g, 4.0 mmol) was added slowly under stirring. The reaction flask was sealed, and the mixture was stirred at room temperature overnight. Ethanol was added slowly, and the mixture was concentrated under reduced pressure to dryness. The residue was co-evaporated with ethanol and purified by flash chromatography on a silica gel column using methylene chloride-methanol (80:1) as eluent providing 1.3 g desired bromo product 156 in 89% yield. 1H NMR (CDCl3) δ 9.10 (br, 1 H), 7.82 (s, 1 H), 6.07 (m, 1 H), 5.26-5.35 (m, 2H), 4.30-4.41(m, 3H), 2.20 (s, 3H), 2.11 (s, 3H), 2.09 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With di-tert-butyl peroxide at 140℃; for 24h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With dipotassium hydrogenphosphate; fac-tris[2-phenylpyridinato-C2,N]iridium(III) In dimethyl sulfoxide at 20℃; for 24h; Schlenk technique; Irradiation; Inert atmosphere; | |
77% | With tris[2-phenylpyridinato-C2,N]iridium(III); dipotassium hydrogenphosphate In dimethyl sulfoxide for 12h; Inert atmosphere; | 19 Embodiment 19 To 25 ml in the reaction tube, adding 2.6 mg (1mol %) Ir (PPy)3, k2HPO4(0.8mmol), compound A-10 (0.4mmol, 1 equivalent), after nitrogen replacement three times by adding 2 ml of dimethyl sulfoxide (DMSO), injection (0.80mmol) compound B-1, under irradiation in blue light stirring 12 hours, to obtain compound C-12, the yield is 77%. C-13 are new compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With sodium hydroxide In water at 20℃; for 4h; | General Nucleoside Acetylation Protocol General procedure: Nucleoside/nucleotide (2; 100 mM) and N-acetyl imidazole (1a;10 equiv) were dissolved in water (pH 8; adjusted with 4 MNaOH). The solution was incubated at r.t. for 4 h, and NMR spectra were periodically acquired. The product was purified byreverse-phase (C18) flash coumn chromatography (eluted at pH4 with 100 mM NH4HCO2/MeCN = 98:2 to 80:20). The fractions containing 5 were lyophilised to yield a white powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1,2-dichloro-ethane at 83℃; for 4h; Inert atmosphere; Schlenk technique; | Synthesis of 3a General procedure: To a solution of silyl-thymidine (10 mmol) in DCE (100 mL) was added 1a(12 mmol diluted in 25 mL DCE) dropwise at room temperature. The resulting mixture was stirred for 4 h at 83 °C. Upon completion of the reaction, as indicated by TLC (n-hexane/ethylacetate: 40:60),the reaction mixture was cooled to room temperature and H2O (50 mL) was added, and the mixturewas, stirred for 0.5 h. The resulting reaction mixture was diluted with DCE (50 mL) and washed with water and saturated NaCl solution. The organic layer was dried with MgSO4 and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography (MeOH/CH2Cl2,1:10 v/v) to obtain an analytical sample for a total yield of 95%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tris(2,2'-bipyridyl)ruthenium dichloride; caesium carbonate In dimethyl sulfoxide at 20℃; for 24h; Irradiation; Inert atmosphere; Schlenk technique; Green chemistry; | General procedure for the direct perfluoroalkylation of uracilsand uracil nucleosides General procedure: To a 25 mL of Schlenk tube equipped with a Teflon septum were added Ru(bpy)3Cl2 (1.5 mg, 0.5 mol%), Cs2CO3 (130 mg, 1.0 equiv) and 1 (0.4 mmol, 1.0 equiv) followed by DMSO 3.0 mL) with stirring. Perfluoroalkyl iodine (2.0 equiv.) was then added subsequently under Ar. The Schlenk tube was screw capped and the reaction was then under irradiated with a 12 W blue LEDs (460 nm-470 nm). After stirring for 24 h, the reaction mixture was diluted with ethyl acetate, washed with brine, the organic phases were collected and dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified with silica gel chromatography to provide pure product. |
82% | With caesium carbonate In dimethyl sulfoxide at 20℃; for 24h; Schlenk technique; Inert atmosphere; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0 - 20℃; for 2h; | 9 (2R,3R,4R,5R)-2-(acetoxymethyl)-5-(2,4-dioxo-3-((5 -phenylthiophen-2- yl)methyl)-3,4-dihydropyrimidin- 1 (2H)-yl)tetrahydrofuran-3,4-diyl diacetate (9-3a) To a solution of compound 9-2a (1.8 g, 9.5 mmol), 2’,3’,5’-Tri-O-acetyluridine (3.18 g, 8.6 mmol) and PPh3 (4.5 g, 17.2 mmol) in THF (20 mL) was added dropwise DEAD (2.9 g, 17.2 mmol) at 0°C. The resulting mixture was stirred for 2 hours at room temperature. The mixture was poured into ice water (100 mL) and was extracted with ethyl acetate (100 mL x 2). The combined organic phase was dried over sodium sulfate, concentrated and purified by chromatography on silica gel (DCM/MeOH = 20:1) to give compound 9-3a (3.0 g, 64 % yield) as a yellow solid; LCMS (ESI): m/z 543 [M+Hj. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 0.5h; | 10 (2R,3 S,4R,5R)-2-(acetoxymethyl)-5-(2,4-dioxo-3-((2-phenyloxazol-5 -yl)methyl)3 ,4-dihydropyrimidin- 1 (2H)-yl)tetrahydrofuran-3,4-diyl diacetate (l0-3b) To a solution of 2’,3’,5’-Tri-O-acetyluridine (884 mg, 2.39 mmol) in DMF (8 mL) were added compound l0-2b (626 mg, 2.63mmol) and K2C03 (989 g, 7.l7mmol). The reaction mixture was stirred at 70°C for 0.5 hours. The mixture poured into ice-water (5OmL) and extracted with EA (3x10 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (PE/EA = 50:1) to afford compound l0-3b (1.3 g, 94% yield) as an oil. LCMS (ESI): m/z 528 [M+Hj. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 1h; | 4 (2R,3R,4R,5R)-2-(acetoxymethyl)-5 -(3-((4-benzylpyridin-2-yl)methyl)-2,4-dioxo- 3 ,4-dihydropyrimidin- 1 (2H)-yl)tetrahydrofuran-3,4-diyl diacetate (4-6) To a solution of 2’,3’,5’-Tri-O-acetyluridine (7.6 g, 20.4 mmol) in DMF (60 mL) was added compound 4-5 (5.9 g, 27.3 mmol) and K2C03(15.0 g, 108 mmol). The reaction mixture was stirred at 70°C for 1 hour. The mixture was poured into ice-water (50 mL) and then extracted with EtOAc (100 mL x 3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (PE/EA = 50:1) to afford compound 4-6 (7.6 g, 68% yield) as an oil. LCMS (ESI): m/z 552 [M+Hj |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 1h; | 5 (2R,3R,4R,5R)-2-(acetoxymethyl)-5-(2,4-dioxo-3 -((4-phenoxypyridin-2- yl)methyl)-3,4-dihydropyrimidin- 1 (2H)-yl)tetrahydrofuran-3,4-diyl diacetate (5-3) To a solution of 2’,3’,5’-Tri-O-acetyluridine (2.1 g, 5.7 mmol) in DMF (20 mL) was added compound 5-2 (1.5 g, 5.7 mmol) and K2C03 (2.6 g, 18.9 mmol). The reaction mixture was stirred at 70°C for 1 hour. The mixture was added to ice-water (20 mL) and then extracted with EA (3x20 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (PE/EA = 10:1) to afford compound 5-3 (1.4 g, 54% yield) as a white solid. LCMS (ESI): m/z 554 [M+Hj |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53.8% | With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 1h; | 6 (2R,3R,4R,5R)-2-(acetoxymethyl)-5 -(2,4-dioxo-3 -((4-(phenylamino)pyridin-2-yl)methyl)-3,4-dihydropyrimidin- 1 (2H)-yl)tetrahydrofuran-3,4-diyl diacetate (6-3) To a solution of 2’,3’,5’-Tri-O-acetyluridine in DMF (30 mL) were added compound 6-2 (1.5 g, 5.68 mmol) and K2C03 (2.6 g, 18.9 mmol). The reaction mixture was stirred at 70°C for 1 hour. After cooling down, the mixture was poured into ice-water (20 mL) and extracted with EA (3 x 20 mL). The combined organic layers was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (PE/EA = 10:1) to afford compound 6-3 (1.4 g, 53.8% yield) as a white solid. LCMS (ESI): m/z = 553 [M+Hj + |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 1h; | 7 j0231j dihydropyrimidin- 1 (2H)-yl)tetrahydrofuran-3,4-diyl diacetate (7-3b) To a solution of 2’,3’,5’-Tri-O-acetyluridine (2.9 g, 7.9 mmol) in DMF (10 mL) were added compound 7-2 (2.5 g, 9.8 mmol) and K2C03 (5.4 g, 39 mmol). The reaction mixture was stirred at 70°C for 1 hour. The mixture was added to ice-water (50 mL) and then extracted with EA (3x50 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (PE/EA = 50:1) to afford compound 7-3b (4.9 g, 92% yield) as an oil. LCMS (ESI):m/z 544 [M+Hf’. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 70℃; | 2 Step C To a solution of chlorine compound 1-3 (1.05 eq) in DMF (10 V) was added 2’,3’,5’-Tri-O- acetyluridine (1.0 eq) and K2C03 (1.5 eq). The reaction mixture was stirred at 70°C for 2-3 hours. The mixture was added to ice-water (10 V) and then extracted with EtOAc (1OV x 2). The combined organic fractions were dried over anhydrous Na2504 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to give acetyl-uridine compound 1-5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With 1,1'-bis-(diphenylphosphino)ferrocene; nickel(II) bromide trihydrate; tetrabutylammonium acetate; zinc In N,N-dimethyl acetamide at 80℃; for 66h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tin(IV) chloride In acetonitrile at 5℃; for 0.25h; Sonication; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With caesium carbonate In dimethyl sulfoxide at 20℃; for 24h; Schlenk technique; Inert atmosphere; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With caesium carbonate In dimethyl sulfoxide at 20℃; for 24h; Schlenk technique; Inert atmosphere; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75 %Spectr. | In dichloromethane; acetonitrile at 20℃; for 3h; | 4.1. General Procedure for the Synthesis of Uracil-Iodonium(III) Triflates General procedure: To a stirred solution of 1,3-dimethyluracil 1a (0.50 mmol) and 4-chloroiodobenzene diacetate 2e (0.55 mmol) in dichloromethane or acetonitrile (2 mL), a solution of trifluoromethanesulfonic acid (ca. 150 mg, 1.0 mmol, 2 equiv) in acetonitrile (1 mL) was added dropwise at room temperature, and the resulting slightly colored solution was stirred for 3 h. After addition of methanol (~2 mL), the solvents were removed under reduced pressure. The residue was then treated with diethyl ether with stirring for precipitation of the iodonium(III) salt. The precipitate was filtered and dried in vacuo to give a pure iodonium(III) salt in powder form. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: uracil; 2′,3′,5′-tri-O-acetyl-5-nitrouridine With N,O-bis-(trimethylsilyl)-acetamide In acetonitrile at 20℃; for 1h; Microwave irradiation; Stage #2: With trimethylsilyl trifluoromethanesulfonate In acetonitrile at 80℃; for 2h; Microwave irradiation; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | Stage #1: Tri-O-acetyluridine With dmap; 2,4,6-triisopropylphenylsulfonyl chloride; triethylamine In 1,4-dioxane at 25℃; for 18h; Inert atmosphere; Stage #2: hydrazinecarboxylic acid methyl ester In 1,4-dioxane at 20℃; for 18h; Inert atmosphere; | Methyl (E)-2-(1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-2,3-dihydropyrimidin-4(1H)-ylidene)hydrazine-1-carboxylate (64) To a mixture of compound 63 (100 mg, 0.27 mmol), dimethylaminopyridine (DMAP, 66 mg, 0.54 mmol) and triethylamine (TEA, 75 µL, 0.54 mmol) in anhydrous dioxane was added 2,4,6-triisopropylbenzenesulfonyl chloride (100 mg, 0.33 mmol) and stirred at room temperature. After stirred for 18 h, methylhydrazine carboxylate (234 mg, 2.7 mmol) was added and stirred for 18 h. Solvent was rotary evaporated under high vacuum and the residue carried forward to next step without any purification (Rf = 0.20, TLC eluent = 5% MeOH in CH2Cl2; HRMS [M+H]+ for C17H22N4O10 calculated, 443.1414, found 443.1415). The reaction residue from the previous step was dissolved in 1N ammonia in methanol (5 mL) and stirred at room temperature for overnight (18 h). Solvent was evaporated, and the residue was purified by silica-gel flash chromatography to afford compound 64 as a white solid (5 mg, 6.0%, Rf = 0.35, TLC eluent = 20% MeOH in CH2Cl2). 1H NMR (400 MHz, CD3OD) δ 8.21 (dd, J = 39.2, 7.6 Hz, 1H), 6.01 (dd, J = 54.8, 7.7 Hz, 1H), 5.89 - 5.80 (m, 1H), 4.17 - 4.08 (m, 2H), 4.03 (dt, J = 5.6, 2.9 Hz, 1H), 3.89 (dd, J = 12.3, 2.5 Hz, 1H), 3.76 (d, J = 3.0 Hz, 1H), 3.73 (s, 3H). HRMS [M+Na]+ for C11H15N4O7Na calculated, 339.0917, found 339.0919 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With trifluoroacetic acid In dichloromethane at 5℃; for 15h; | 1-3 Dissolve 118.3g (0.47mol) of the silanization protection substance in 150ml of dichloromethane, add 185.1g (0.5mol) of 2',3',5'-triacetyluridine, and slowly dropwise add trifluoroacetic acid 2.35 at 5 g(0.01mol), 3h dripping, reaction at 5 for 15h, after the reaction is complete, suction filtration, filter cake with dichloromethane, combine the organic phases, pour into water, stir, separate the organic phase, dry, spin dry, 150ml of methyl tert-butyl ether was added for beating to obtain 89.4g of 2',3',5'-triacetylazacitidine with a yield of 88%. |
Tags: 4105-38-8 synthesis path| 4105-38-8 SDS| 4105-38-8 COA| 4105-38-8 purity| 4105-38-8 application| 4105-38-8 NMR| 4105-38-8 COA| 4105-38-8 structure
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