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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
an antagonist of the estrogen related receptor signaling pathway with the pleiotropic PPARgamma coactivator (PGC)
Synonyms: 5-methyluracil
4.5
*For Research Use Only! Not for Human Use. We Do Not Sell to Patients.
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| CAS No. : | 65-71-4 |
| Formula : | C5H6N2O2 |
| M.W : | 126.11 |
| SMILES Code : | O=C1NC(C(C)=CN1)=O |
| Synonyms : |
5-methyluracil
|
| English Name : | 5-Methylpyrimidine-2,4(1H,3H)-dione |
| MDL No. : | MFCD00006026 |
| InChI Key : | RWQNBRDOKXIBIV-UHFFFAOYSA-N |
| Pubchem ID : | 1135 |
| GHS Pictogram: | |
| Signal Word: | |
| Hazard Statements: | |
| Precautionary Statements: | |
| Class: | |
| UN#: | |
| Packing Group: |
* 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 |
|---|---|---|
| With platinum(IV) oxide Hydrogenation.und Erhitzen des Reaktionsprodukts mit wss.NaOH; | ||
| With rhodium Hydrogenation.und Erhitzen des Reaktionsprodukts mit wss.NaOH; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sulfuric acid; sulfur trioxide |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 99% | With 1,1,1,3,3,3-hexamethyl-disilazane Ambient temperature; | |
| 93% | With triethylamine In benzene for 2h; Inert atmosphere; Reflux; | |
| 89% | With triethylamine In benzene Inert atmosphere; |
| 84% | With 1,1,1,3,3,3-hexamethyl-disilazane In 1,2-dichloro-ethane at 120℃; for 1h; | |
| 78.4% | With triethylamine In toluene | |
| 78% | With triethylamine In toluene | Synthesis of 1, 1’- Trimethylene-bis(thymine) 3a: To a magnetically stirred suspension of thymine (5.2 g, 41.2 mmol) in 125 mL of dry toluene was added chlorotrimethylsilane (9.41 g, 86.66 mmol). Triethylamine (15 mL, 103.1 mmol) was added to the reaction mass in 10 mL of toluene and the mixture was stirred overnight. The mixture was filtered and washed with three 25-mL portions of toluene and the filtrate was evaporated to give O, O’ bis(trimethylsilyl)thymine, 2 (8.74 g, 78%). To compound 2 (8.7 g, 32.3 mmol) in anhydrous DMF (50 mL) was added 1, 3-dibromopropane (3.06 g, 15.1 mmol) at RT. The solution was heated to 170 0C and stirred overnight. The reaction mixture was cooled to 0 0C and MeOH (20 mL) was added to precipitate the product. The solids were recovered by filtration, washed with chloroform-methanol (1:1, 100 mL) and dried under vacuum to yield compound 3a (9.03 g, 75% based on thymine) as an off white solid. |
| 78% | With 1,1,1,3,3,3-hexamethyl-disilazane In 1,2-dichloro-ethane at 120℃; for 1h; | |
| 70% | With triethylamine | |
| 51% | With triethylamine Ambient temperature; | |
| With 1,1,1,3,3,3-hexamethyl-disilazane | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane for 24h; Heating; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane at 140 - 150℃; for 5h; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane for 16h; Heating; | ||
| With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane Heating; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane | ||
| With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane Heating; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane at 130℃; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane Heating; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane In acetonitrile for 0.666667h; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane 1) 120 deg C, 1 h; 2) reflux, 2 h; Yield given. Multistep reaction; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane for 2h; Heating; | ||
| With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane Heating; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane | ||
| In various solvent(s) Heating; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane for 4h; Heating; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane for 21h; Heating; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane at 20℃; | ||
| With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane at 140 - 150℃; | ||
| With pyridine; 1,1,1,3,3,3-hexamethyl-disilazane at 125℃; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane Heating; | ||
| With trimethylsilyl trifluoromethanesulfonate; 1,1,1,3,3,3-hexamethyl-disilazane In acetonitrile for 6h; Heating; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane In 1,2-dichloro-ethane at 80℃; for 3h; | ||
| With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane Heating; | ||
| With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane for 18h; Heating; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane for 3h; Heating; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane at 120℃; for 16h; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane for 20h; Heating; | ||
| With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane at 140 - 150℃; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane In 1,2-dichloro-ethane at 80℃; for 5h; | ||
| With pyridine; 1,1,1,3,3,3-hexamethyl-disilazane Reflux; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane Reflux; Inert atmosphere; | ||
| With triethylamine In benzene | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane for 21h; Inert atmosphere; Reflux; | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane for 21h; Inert atmosphere; Reflux; | ||
| With triethylamine In dichloromethane | ||
| With triethylamine In dichloromethane | ||
| With triethylamine In toluene | ||
| With 1,1,1,3,3,3-hexamethyl-disilazane at 130℃; for 2h; Inert atmosphere; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 94% | With sodium hydroxide; In water; at 20 - 50℃; for 20.5h; | To a solution of sodium hydroxide (96 g, 2.4 mol) in H2O (1000 mL) was added into 5-methyl-2, 3-dihydropyrimidin-4(1H)-one (2, 100.8 g, 0.8 mol). When most of the solid dissolve, diethyl sulfate (252.3 g, 2 mol) was added dropwise in 30min. After stirring for 10h, diethyl sulfate (50.5 g, 0.4 mol) and sodium hydroxide (10 g, 0.25 mol) were added. The mixture was stirred for another 10h, then sodium chloride (200 g) was added. The mixture was extracted with ethyl acetate (3×500 mL). The combined organic layer was concentrated to get white solid 5-trimethyl-2, 3-dihydropyrimidin-4(1H)-one (3, 115.9 g), yield: 94%, mp 153.2-154.4Clit.1 mp 155C |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 15.8 % Chromat. 2: 4.0 % Chromat. 3: 9.1 % Chromat. 4: 66.0 % Chromat. | With sodium chloride In water for 5h; galvanostatic electrolysis, Pt electrodes; Further byproducts given; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 56% | With hydrogen In water for 6h; | Procedure for the Catalytic Hydrogenation of Thymine and 6-Methyluracil :; Dihydrothymine : Thymine, (300 mg, 2.4 mmol) was dissolved in distilled water and 312 mg of 5% Rh on alumina was added. The flask was flushed with H2, and subsequently allowed to stir under a hydrogen balloon for 6 hours and monitored by TLC. The catalyst was then removed by gravity filtration and the filtrate removed under reduced pressure. The resulting white solid was recrystallized from ethanol in 56% yield. Yield = 56%. m. p. = 264- [265°C.'H] NMR [(D20)] 8 : 1.1 (d, 3H, J=7.2 Hz), 2.7 (m, 1H), 3.1 (dd, 1H, JAB= 12.8 Hz, JAx= 10.1 Hz), 3.4 (dd, [1H, JBX=] 6.3 Hz, [JBA=] 12.8 Hz). |
| With sodium dihydrogenphosphate; water Irradiation; | ||
| With hydrogen |
| With dihydropyrimidine dehydrogenase from Escherichia coli; NADH Enzymatic reaction; | General procedure: Steady-state kinetic measurements of EcDPD were undertaken under aerobic and anaerobic conditions. These data show that the kinetic parameters with both uracil and thymine are similar (kcatU=1.9±0.2 s-1, kcat/KMU=25,600±400M-1s-1, kcatT=1.6±0.1 s-1, kcat/KMT=21,300±200M-1s-1). Given that thymine is relatively deactivated for hydride transfer [9,22], these data imply that hydride transfer to the pyrimidine is not rate limiting for turnover in this form of the enzyme. Aerobic measurements indicate significant NADH oxidase activity resulting in turnover numbers that overestimate the rate of turnover by two-fold (Fig. 3 A). With respect to NADH, the steady-state data indicate approximately ten-fold higher kcat/KM than observed for the pyrimidine substrates (kcat/KMNADH=2.17×105±1.3×104M-1s-1) (Fig. 3B). When measured with dioxygen as the oxidant, the rate of NADH oxidation is approximately 70% the rate observed with uracil as the oxidant indicating that valid steady-state measurements for either type of substrate can only be made under anaerobic conditions. |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 79% | With potassium carbonate In dimethyl sulfoxide at 20℃; for 17h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 79% | Stage #1: thymin With N,O-bis-(trimethylsilyl)-acetamide In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: benzyl bromide With tetra-(n-butyl)ammonium iodide In chlorobenzene at 20 - 160℃; for 1.66667h; Microwave irradiation; Inert atmosphere; | |
| 60% | With potassium carbonate In N,N-dimethyl-formamide at 25℃; | |
| With potassium carbonate In N,N-dimethyl-formamide |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 62% | Stage #1: thymin With N,O-bis-(trimethylsilyl)-acetamide In acetonitrile at 80℃; Stage #2: 6-bromo-hex-4-enoic acid tert-butyl ester In acetonitrile at 80℃; for 2h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 96% | Intermediate 12,4-Dibromo-5-methylpyrimidineTo thymine (3.7 g, 29 mmol) and phosphorus(V) oxybromide (25.0 g, 87.2 mmol) in acetonitrile (CH3CN) (150 mL) at 0 0C was added portion wise K2CO3 (12.1 g, 87.2 mmol). The mixture was allowed to warm to room temperature and then heated to 80 0C for 3 days. The reaction mixture was poured onto ice and the pH of the resulting slurry was adjusted to pH 7 by addition of K2CO3(S). The aqueous layer was extracted with methylene chloride (CH2Cl2). The organic layer was washed with brine, dried (MgSO4), filtered and concentrated. Purification by flash chromatography on silica gel (0 - 30 % ethyl acetate (EtOAc)/hexanes) afforded the desired product (7.1 g, 96%) as a white solid. LC-MS (ES) m/z = 251 , 253 and 255 [M+H]+. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: NaH / dimethylformamide / 2 h / 20 °C 1.2: 67 percent / dimethylformamide / 20 h / 110 °C 2.1: 74 percent / N,N-diisopropylethylamine / CH2Cl2 / 2 h |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1.1: NaH / dimethylformamide / 2 h / 20 °C 1.2: 49 percent / dimethylformamide / 20 h / 110 °C 2.1: 77 percent / N,N-diisopropylethylamine / CH2Cl2 / 2 h | ||
| Multi-step reaction with 3 steps 1: 60 percent / potassium carbonate / dimethylformamide / 1 h / 85 °C 2: pyridine 3: diisopropyl ethylamine / acetonitrile |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 69.4% | Stage #1: 2,2'-anhydro-5-methyluridine; 2-methoxy-ethanol With tris(2-methoxyethyl)borate; sodium hydrogencarbonate at 130℃; for 21h; Argon atmosphere; Stage #2: With water for 0.5h; Heating / reflux; | 228 EXAMPLE 228; [2'-0- (2-METHOXYETHYL)] modified amidites; [2'-O- (2-METHOXYETHYL)-5-METHYLURIDINE] intermediate 2,2'-Anhydro-5-methyl-uridine (2000 g, 8.32 mol), tris (2-methoxyethyl) borate (2504 g, 10.60 mol), sodium bicarbonate (60 g, 0.70 mol) and anhydrous 2- methoxyethanol (5 L) were combined in a 12 L three necked flask and heated to 130 [°C] (internal temp) at atmospheric pressure, under an argon atmosphere with stirring for 21 h. TLC indicated a complete reaction. The solvent was removed under reduced pressure until a sticky gum formed [(50-85°C] bath temp and 100-11 mm Hg) and the residue was redissolved in water (3 L) and heated to boiling for 30 min in order the hydrolyze the borate esters. The water was removed under reduced pressure until a foam began to form and then the process was repeated. HPLC indicated about 77% product, 15% dimer (5'of product attached to 2'of starting material) and unknown derivatives, and the balance was a single unresolved early eluting peak. The gum was redissolved in brine (3 L), and the flask was rinsed with additional brine (3 L). The combined aqueous solutions were extracted with chloroform (20 L) in a heavier-than continuous extractor for 70 h. The chloroform layer was concentrated by rotary evaporation in a 20 L flask to a sticky foam (2400 g). This was coevaporated with MeOH (400 mL) and EtOAc (8 L) at [75°C] and 0.65 atm until the foam dissolved at which point the vacuum was lowered to about 0.5 atm. After 2.5 L of distillate was collected a precipitate began to form and the flask was removed from the rotary evaporator and stirred until the suspension reached ambient temperature. EtOAc (2 L) was added and the slurry was filtered on a 25 cm table top Buchner funnel and the product was washed with EtOAc [(3 X 2] L). The bright white solid was air dried in pans for 24 h then further dried in a vacuum oven [(50°C,] 0.1 mm Hg, 24 h) to afford 1649 [G] of a white crystalline solid (mp 115.5-116. [5°C).] The brine layer in the 20 L continuous extractor was further extracted for 72 h with recycled chloroform. The chloroform was concentrated to 120 g of oil and this was combined with the mother liquor from the above filtration (225 g), dissolved in brine (250 mL) and extracted once with chloroform (250 mL). The brine solution was continuously extracted and the product was crystallized as described above to afford an additional 178 g of crystalline product containing about [2%] of thymine. The combined yield was [1827] g (69.4%). HPLC indicated about 99. 5% purity with the balance being the dimer. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 2% | With tris(2-methoxyethyl)borate; sodium hydrogencarbonate In 2-methoxy-ethanol at 130℃; for 21h; | 1 Preparation of 2'-O-(2-methoxyethyl)-5-methyluridine Intermediate 2,2'-Anhydro-5-methyl-uridine (2000 g, 8.32 mol), tris(2-methoxyethyl)borate (2504 g, 10.60 mol), sodium bicarbonate (60 g, 0.70 mol) and anhydrous 2-methoxyethanol (5 L) were combined in a 12 L three necked flask and heated to 130 C. (internal temp) at atmospheric pressure, under an argon atmosphere with stirring for 21 h. TLC indicated a complete reaction. The solvent was removed under reduced pressure until a sticky gum formed (50-85 C. bath temp and 100-11 mm Hg) and the residue was redissolved in water (3 L) and heated to boiling for 30 min in order the hydrolyze the borate esters. The water was removed under reduced pressure until a foam began to form and then the process was repeated. HPLC indicated about 77% product, 15% dimer (5' of product attached to 2' of starting material) and unknown derivatives, and the balance was a single unresolved early eluting peak. The gum was redissolved in brine (3 L), and the flask was rinsed with additional brine (3 L). The combined aqueous solutions were extracted with chloroform (20 L) in a heavier-than continuous extractor for 70 h. The chloroform layer was concentrated by rotary evaporation in a 20 L flask to a sticky foam (2400 g). This was coevaporated with MeOH (400 mL) and EtOAc (8 L) at 75 C. and 0.65 atm until the foam dissolved at which point the vacuum was lowered to about 0.5 atm. After 2.5 L of distillate was collected a precipitate began to form and the flask was removed from the rotary evaporator and stirred until the suspension reached ambient temperature. EtOAc (2 L) was added and the slurry was filtered on a 25 cm table top Buchner funnel and the product was washed with EtOAc (32 L). The bright white solid was air dried in pans for 24 h then further dried in a vacuum oven (50 C., 0.1 mm Hg, 24 h) to afford 1649 g of a white crystalline solid (mp 115.5-116.5 C.). The brine layer in the 20 L continuous extractor was further extracted for 72 h with recycled chloroform. The chloroform was concentrated to 120 g of oil and this was combined with the mother liquor from the above filtration (225 g), dissolved in brine (250 mL) and extracted once with chloroform (250 mL). The brine solution was continuously extracted and the product was crystallized as described above to afford an additional 178 g of crystalline product containing about 2% of thymine. The combined yield was 1827 g (69.4%). HPLC indicated about 99.5% purity with the balance being the dimer. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 69.4% | Stage #1: O-2,2'-cyclo-5-methyluridine; tris(2-methoxyethyl)borate In 2-methoxy-ethanol at 130℃; for 21h; Stage #2: With water for 0.5h; Heating / reflux; | 1 2,2'-Anhydro-5-methyl-uridine (2000 g, 8.32 mol), tris(2-methoxyethyl)borate (2504 g, 10.60 mol), sodium bicarbonate (60 g, 0.70 mol) and anhydrous 2-methoxyethanol (5 L) were combined in a 12 L three necked flask and heated to 130° C. (internal temp) at atmospheric pressure, under an argon atmosphere with stirring for 21 h. TLC indicated a complete reaction. The solvent was removed under reduced pressure until a sticky gum formed (50-85° C. bath temp and 100-11 mm Hg) and the residue was redissolved in water (3 L) and heated to boiling for 30 min in order the hydrolyze the borate esters. The water was removed under reduced pressure until a foam began to form and then the process was repeated. HPLC indicated about 77% product, 15% dimer (5' of product attached to 2' of starting material) and unknown derivatives, and the balance was a single unresolved early eluting peak. [0168] The gum was redissolved in brine (3 L), and the flask was rinsed with additional brine (3 L). The combined aqueous solutions were extracted with chloroform (20 L) in a heavier-than continuous extractor for 70 h. The chloroform layer was concentrated by rotary evaporation in a 20 L flask to a sticky foam (2400 g). This was coevaporated with MeOH (400 mL) and EtOAc (8 L) at 75° C. and 0.65 atm until the foam dissolved at which point the vacuum was lowered to about 0.5 atm. After 2.5 L of distillate was collected a precipitate began to form and the flask was removed from the rotary evaporator and stirred until the suspension reached ambient temperature. EtOAc (2 L) was added and the slurry was filtered on a 25 cm table top Buchner funnel and the product was washed with EtOAc (3×2 L). The bright white solid was air dried in pans for 24 h then further dried in a vacuum oven (50° C., 0.1 mm Hg, 24 h) to afford 1649 g of a white crystalline solid (mp 115.5-116.5° C.). [0169] The brine layer in the 20 L continuous extractor was further extracted for 72 h with recycled chloroform. The chloroform was concentrated to 120 g of oil and this was combined with the mother liquor from the above filtration (225 g), dissolved in brine (250 mL) and extracted once with chloroform (250 mL). The brine solution was continuously extracted and the product was crystallized as described above to afford an additional 178 g of crystalline product containing about 2% of thymine. The combined yield was 1827 g (69.4%). HPLC indicated about 99.5% purity with the balance being the dimer. |
| 69.4% | Stage #1: O-2,2'-cyclo-5-methyluridine; tris(2-methoxyethyl)borate In 2-methoxy-ethanol at 130℃; for 21h; Stage #2: With water for 0.5h; Heating / reflux; | 1 2,2'-Anhydro-5-methyl-uridine (2000 g, 8.32 mol), tris(2-methoxyethyl)borate (2504 g, 10.60 mol), sodium bicarbonate (60 g, 0.70 mol) and anhydrous 2-methoxyethanol (5 L) were combined in a 12 L three necked flask and heated to 130° C. (internal temp) at atmospheric pressure, under an argon atmosphere with stirring for 21 h. TLC indicated a complete reaction. The solvent was removed under reduced pressure until a sticky gum formed (50-85° C. bath temp and 100-11 mm Hg) and the residue was redissolved in water (3 L) and heated to boiling for 30 min in order the hydrolyze the borate esters. The water was removed under reduced pressure until a foam began to form and then the process was repeated. HPLC indicated about 77% product, 15% dimer (5' of product attached to 2' of starting material) and unknown derivatives, and the balance was a single unresolved early eluting peak. [0168] The gum was redissolved in brine (3 L), and the flask was rinsed with additional brine (3 L). The combined aqueous solutions were extracted with chloroform (20 L) in a heavier-than continuous extractor for 70 h. The chloroform layer was concentrated by rotary evaporation in a 20 L flask to a sticky foam (2400 g). This was coevaporated with MeOH (400 mL) and EtOAc (8 L) at 75° C. and 0.65 atm until the foam dissolved at which point the vacuum was lowered to about 0.5 atm. After 2.5 L of distillate was collected a precipitate began to form and the flask was removed from the rotary evaporator and stirred until the suspension reached ambient temperature. EtOAc (2 L) was added and the slurry was filtered on a 25 cm table top Buchner funnel and the product was washed with EtOAc (3×2 L). The bright white solid was air dried in pans for 24 h then further dried in a vacuum oven (50° C., 0.1 mm Hg, 24 h) to afford 1649 g of a white crystalline solid (mp 115.5-116.5° C.). [0169] The brine layer in the 20 L continuous extractor was further extracted for 72 h with recycled chloroform. The chloroform was concentrated to 120 g of oil and this was combined with the mother liquor from the above filtration (225 g), dissolved in brine (250 mL) and extracted once with chloroform (250 mL). The brine solution was continuously extracted and the product was crystallized as described above to afford an additional 178 g of crystalline product containing about 2% of thymine. The combined yield was 1827 g (69.4%). HPLC indicated about 99.5% purity with the balance being the dimer. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 44% | With potassium carbonate In <i>N</i>-methyl-acetamide; methanol | 1 1-(4-Dihydroxyborylbutyl)thymine EXAMPLE 1 1-(4-Dihydroxyborylbutyl)thymine Potassium carbonate (0.6 g, 4.4 mmol) was added to a solution of thymine (0.56 g, 4.4 mmol) in dimethylformamide (15 mL) and stirred for 30 minutes. To this reaction mixture, 4-bromobutyl boronic acid (0.4 g, 2.2 mmol) dissolved in dimethylformamide (5 mL) was added dropwise, and stirring was continued 2 days at room temperature. After the potassium carbonate was filtered, the dimethylformamide was evaporated under high vacuum. The residue was purified on a silica gel column eluding with a discontinuous gradient of chloroform/methanol (95:5, 85:15). The appropriate TLC-homogenous fractions were pooled and evaporated to give 0.22 g of pure product. Yield 44%; mp 130°-132° C.; 1 H NMR (DMSO-d6) 0.55-0.68 (t, B CH2), 1.22-1.35 (m, B CH2 CH2), 1.42-1.60 (m, B CH2 CH2 CH2), 1.72-1.78 (s, CH3 C5 thymine), 3.52-3.63 (CH2 CH2 N), 7.40-7.43 (s, (HO)2 B), 7.48-7.51 (s, H C6 thymine), 11.12-11.18 (s, HN thymine). Elemental Analysis (C9H15BO4N2); Calcd. C, 47.82%; H, 6.69%; N, 12.40%; Found C, 47.71%; H, 6.72%; N, 12.35%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 35% | With N,N,N,N,-tetramethylethylenediamine; copper diacetate In methanol; water at 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 16% 2: 23% 3: 28% | With caesium carbonate In dimethyl sulfoxide at 120℃; for 3h; | General method C General procedure: Nucleobase (1.5 mmol) and base (1.5 mmol) were heated at 100 °C in dry DMF/DMSO (15 ml). Mesyl derivative (1 mmol) dissolved in dry DMF/DMSO (10 ml) was then added dropwise and the mixture was heated at 120 °C for 3 h. The solvent was evaporated and product purified on a silica gel using flash chromatography. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 78% | With P4S10-pyridine complex In dimethylsulfone at 165 - 175℃; for 0.25h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 1: 33% 2: 19% | Stage #1: thymin With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 70℃; for 1h; Stage #2: 3-(tert-butoxycarbonylamino)propyl methanesulfonate With tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide at 70℃; for 12h; | tert-Butyl (3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propyl)carbamate 10a In a round bottom flask, 71 mg of thymine (CAS: 65-71-4, 126.1 g/mol, 0.56 mmol) and 52 mg of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene, CAS: 6674-22-2, 152.2 g/mol, 0.341 mmol) were suspended in 5 mL of dry DMF. This mixture was stirred for 1 h at 70 °C. Separately, 46 mg of mesylate 9b (253.0 g/mol; 0.18 mmol) and 22 mg of TBAI (tetrabutylammonium iodide, CAS: 311-28-4, 396.4 g/mol, 0.056 mmol), were dissolved in 3 mL of dry DMF in round bottom flask. This mixture was added to the initial mixture, and the reaction was stirred for 12 h at 70 °C. Excess water was added to the reaction mixture, which was later extracted with AcOEt (3 times). The organic extract was washed with water (5 times). The organic extract was washed with water (5 times), dried over anhydrous Na2SO4, filtered, and the solvent was removed under reduced pressure. Flash chromatography afforded 3.5 mg of cyclic carbamate 10c (Hexanes/AcOEt 95:5, 19% yield) and 17 mg of product 10a (Hexanes/AcOEt 9:1, 33%). |
[ 50-89-5 ]
[ 32645-69-5 ]
[ 32645-65-1 ]




[ 5116-24-5 ]
[ 41308-58-1 ]
[ 67145-02-2 ]
[ 65-71-4 ]

[ 5627-00-9 ]
[ 38241-09-7 ]
[ 4494-26-2 ]| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| at 25℃; for 0.5h;Sonication; Inert atmosphere; | General procedure: dT was purchased from Pharma Waldhof and used as such. All solutions were prepared in water purified by a Cascada Lab Water Systems and of resistivity 18.2 MOmega cm. Solutions of dT (10-4 mol/L, 250 mL) was subjected to sonolysis at four different frequencies (200, 350, 620 and 1000 kHz) at three different power densities, 10.5, 24.5 and 42 W/mL for 2 h. Two frequencies (620 kHz and 1 MHz), among the four studied, fall under the range used for the surgical non disruptive applications. The sonolysis was carried out in a glass reactor with an L3 ELAC Nautik ultrasound generator powered by an Allied Signal R/F generator (T & C power conversion, Model AG 1006). For the experiments under argon saturated atmosphere, the solution was bubbled with argon gas for half an hour at a pressure of 5 psi prior to sonolysis and Ar was bubbled throughout the experiment. Sonolysis was carried out only at a power density of 42 W/mL under argon atmosphere, where there was maximum degradation in the case of aerated conditions. Two transducers were used with resonances 212 and 620 kHz and 350 and 1000 kHz respectively. The temperature was maintained at 25 ± 1 C. |
[ 50-89-5 ]
[ 32645-69-5 ]
[ 32645-65-1 ]





[ 5116-24-5 ]
[ 65-71-4 ]
[ 5627-00-9 ]
[ 38241-09-7 ]
[ 4494-26-2 ]| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With air; at 25℃; for 1h;Sonication; | General procedure: dT was purchased from Pharma Waldhof and used as such. All solutions were prepared in water purified by a Cascada Lab Water Systems and of resistivity 18.2 MOmega cm. Solutions of dT (10-4 mol/L, 250 mL) was subjected to sonolysis at four different frequencies (200, 350, 620 and 1000 kHz) at three different power densities, 10.5, 24.5 and 42 W/mL for 2 h. Two frequencies (620 kHz and 1 MHz), among the four studied, fall under the range used for the surgical non disruptive applications. The sonolysis was carried out in a glass reactor with an L3 ELAC Nautik ultrasound generator powered by an Allied Signal R/F generator (T & C power conversion, Model AG 1006). For the experiments under argon saturated atmosphere, the solution was bubbled with argon gas for half an hour at a pressure of 5 psi prior to sonolysis and Ar was bubbled throughout the experiment. Sonolysis was carried out only at a power density of 42 W/mL under argon atmosphere, where there was maximum degradation in the case of aerated conditions. Two transducers were used with resonances 212 and 620 kHz and 350 and 1000 kHz respectively. The temperature was maintained at 25 ± 1 C. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 96.1% | With dihydrogen peroxide; 1-hydroxy-1,2,3-benzotriazine-4(3H)-one; In water; at 130℃; for 3h;Autoclave; | Add 100 g of thymine and 300 mL of water to the autoclave, and add 35 mL of hydrogen peroxide at a concentration of 30percent.15 g of 1-hydroxy-1,2,3-benzotriazine-4(3H)-one and 35 g of the catalyst prepared in Example 3, replacing the inside of the autoclave with an oxygen atmosphere, and heating to 130 ° C for 3 h.The reaction solution was cooled, filtered, concentrated, and placed in an ice-water mixture to cool.150 g of a white solid was precipitated, the yield was 96.1percent, and the purity was 99.3percent. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80% | With iodine; potassium carbonate; triethylamine; triphenylphosphine In N,N-dimethyl-formamide for 18h; Reflux; regioselective reaction; | General procedure for one-pot N-alkylation of nucleobases via alcohols using TPP/I2 General procedure: In a double-necked round bottom flask (100 mL) equipped with a condenser was added a mixture, consisting of alcohol (1 mmol),TPP (1 mmol), I2 (1 mmol) Et3N (1 mmol), K2CO3 (1 mmol), and thedesire nucleo base (1 mmol) in anhydrous DMF (5 mL).33 The mixture was heated at reflux. Heating was continued until TLC indicated no further improvement in the conversion (Table 5). The solvent was evaporated under vacuum and the remaining foam was dissolved in CHCl3 (100 mL) and subsequently washed with water (2100 mL). The organic layer was dried (Na2SO4) and evaporated. The crude product was purified by short column chromatography on silica gel eluting with proper solvents. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1.1: potassium hydroxide / water / 1 h / 40 °C 2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; 1-hydroxy-pyrrolidine-2,5-dione / N,N-dimethyl-formamide / 1 h / 20 °C / Schlenk technique 2.2: 24 h / 20 °C / Schlenk technique 3.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C / Schlenk technique |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 98% | In water at 40℃; | 4 Preparation of Catalyst 4: MTBD (2mmol, 310mg) and thymine T (2mmol, 252mg) were added to a 50mL round-bottom flask, and 15mL hot water was added as a solvent. The mixture was stirred at 40°C for 8 hours. After the reaction was completed, the solvent was removed by vacuum to obtain a crude product. The crude product was placed in a vacuum drying oven for 24 hours to dry and remove moisture. 0.55g of the target catalyst 5 was obtained. The yield (purification) was 98%. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: ammonium iodide-coated graphitic carbon nitride / 3 h / 120 °C / Green chemistry 2: acetonitrile / 12 h / 80 °C | ||
| Multi-step reaction with 2 steps 1.1: / 3 h / 120 °C / Green chemistry 2.1: 1,1,1,3,3,3-hexamethyl-disilazane; / acetonitrile / 12 h / 80 °C / Green chemistry 2.2: Green chemistry |
Tags: Thymine | 5-methyluracil | Pyrimidines | Amides | Drug Standard | Ketones | GAK | Organic Building Blocks | Heterocyclic Building Blocks | Protein Tyrosine Kinase/RTK | Drug Analysis | 65-71-4
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