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[ CAS No. 54-20-6 ] {[proInfo.proName]}

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Chemical Structure| 54-20-6
Chemical Structure| 54-20-6
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Product Details of [ 54-20-6 ]

CAS No. :54-20-6 MDL No. :MFCD00006024
Formula : C5H3F3N2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :LMNPKIOZMGYQIU-UHFFFAOYSA-N
M.W : 180.08 Pubchem ID :5899
Synonyms :

Calculated chemistry of [ 54-20-6 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.2
Num. rotatable bonds : 1
Num. H-bond acceptors : 5.0
Num. H-bond donors : 2.0
Molar Refractivity : 32.69
TPSA : 65.72 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.37 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.51
Log Po/w (XLOGP3) : 0.04
Log Po/w (WLOGP) : 1.23
Log Po/w (MLOGP) : 0.03
Log Po/w (SILICOS-IT) : 2.31
Consensus Log Po/w : 0.83

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.29
Solubility : 9.33 mg/ml ; 0.0518 mol/l
Class : Very soluble
Log S (Ali) : -0.97
Solubility : 19.2 mg/ml ; 0.106 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.35
Solubility : 0.801 mg/ml ; 0.00445 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.74

Safety of [ 54-20-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 54-20-6 ]

* 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.

  • Upstream synthesis route of [ 54-20-6 ]
  • Downstream synthetic route of [ 54-20-6 ]

[ 54-20-6 ] Synthesis Path-Upstream   1~20

  • 1
  • [ 54-20-6 ]
  • [ 3932-97-6 ]
YieldReaction ConditionsOperation in experiment
95% at 85 - 100℃; for 20 h; Preparation of 2.4-dichloro-5-trifluoromethylpyrimidine (3)
5-Trifluoromethyluracil (250 g, 1.39 mol) and phosphorous oxychloride (655 mL, 6.94 mol, 5 equiv) were charged to a 3 L 4-neck flask equipped with overhead stirrer, a reflux condenser, an addition funnel and an internal theromocouple.
The contents were maintained under a nitrogen atmosphere as concentrated phosphoric acid (85 wt percent, 9.5 mL, 0.1 equiv) was added in one portion to the slurry, resulting in a moderate exotherm.
Diisopropylethylamine (245 mL, 1.39 mol, 1 equiv) was then added dropwise over 15 minutes at such a rate that the internal temperature of the reaction reached 85-90° C. by the end of the addition.
By the end of the amine addition the reaction mixture was a homogenous light-orange solution.
Heating was initiated and the orange solution was maintained at 100° C. for 20 hours, at which time HPLC analysis of the reaction mixture indicated that the starting material was consumed.
External heating was removed and the contents of the flask were cooled to 40° C. and then added dropwise to a cooled mixture of 3N HCl (5 L, 10 equiv) and diethyl ether (2 L) keeping the temperature of the quench pot between 10 and 15° C.
The layers were separated, and the aqueous layer was extracted once with ether (1 L).
The combined organic layers were combined, washed with water until the washes were neutral (5*1.5 L washes), dried with MgSO4 and concentrated to provide 288 g (95percent yield) of a light yellow-orange oil of 96percent purity (HPLC).
This material can be further purified by distillation (bp 109° C. at 79 mmHg).
95% With phosphoric acid; N-ethyl-N,N-diisopropylamine; trichlorophosphate In water at 85 - 100℃; for 20.25 h; 5-Trifluoromethyluracil (250 g, 1.39 mol) and phosphorous oxychloride (655 mL, 6.94 mol, 5 equiv) were charged to a 3 L 4-neck flask equipped with overhead stirrer, a reflux condenser, an addition funnel and an internal theromocouple. The contents were maintained under a nitrogen atmosphere as concentrated phosphoric acid (85 wt percent, 9.5 mL, 0.1 equiv) was added in one portion to the slurry, resulting in a moderate exotherm. Diisopropylethylamine (245 mL, 1.39 mol, 1 equiv) was then added dropwise over 15 min at such a rate that the internal temperature of the reaction reached 85-90° C. by the end of the addition. By the end of the amine addition the reaction mixture was a homogenous light-orange solution. Heating was initiated and the orange solution was maintained at 100° C. for 20 h, at which time HPLC analysis of the reaction mixture indicated that the starting material was consumed. External heating was removed and the contents of the flask were cooled to 40° C. and then added dropwise to a cooled mixture of 3NHCl (5 L, 10 equiv) and diethyl ether (2 L) keeping the temperature of the quench pot between 10 and 15° C. The layers were separated, and the aqueous layer was extracted once with ether (1 L). The combined organic layers were combined, washed with water until the washes were neutral (5.x.1.5 L washes), dried with MgSO4 and concentrated to provide 288 g (95percent yield) of a light yellow-orange oil of 96percent purity (HPLC). This material can be further purified by distillation (bp 109° C. at 79 mmHg).
95% at 85 - 100℃; for 20.25 h; 5-Trifluoromethyluracil (250 g, 1.39 mol) and phosphorous oxychloride (655 mL, 6.94 mol, 5 equiv) were charged to a 3 L 4-neck flask equipped with overhead stirrer, a reflux condenser, an addition funnel and an internal theromocouple. The contents were maintained under a nitrogen atmosphere as concentrated phosphoric acid (85 wt percent, 9.5 mL, 0.1 equiv) was added in one portion to the slurry, resulting in a moderate exotherm. Diisopropylethylamine (245 mL, 1.39 mol, 1 equiv) was then added dropwise over 15 minutes at such a rate that the internal temperature of the reaction reached 85-90° C. by the end of the addition. By the end of the amine addition the reaction mixture was a homogenous light-orange solution. Heating was initiated and the orange solution was maintained at 100° C. for 20 hours, at which time HPLC analysis of the reaction mixture indicated that the starting material was consumed. External heating was removed and the contents of the flask were cooled to 40° C. and then added dropwise to a cooled mixture of 3N HCl (5 L, 10 equiv) and diethyl ether (2 L) keeping the temperature of the quench pot between 10 and 15° C. The layers were separated, and the aqueous layer was extracted once with ether (1 L). The combined organic layers were combined, washed with water until the washes were neutral (5.x.1.5 L washes), dried with MgSO4 and concentrated to provide 288 g (95percent yield) of a light yellow-orange oil of 96percent purity (HPLC). This material can be further purified by distillation (bp 109° C. at 79 mmHg).
72.9% at 110 - 120℃; 10060] To a jacket reactor (500 mE) is added 5-trifluorom- ethyluracil (5-TFU, 40 g, 70percent assay, .-0.16 mol, 1.0 eq.), H3P04 (2.4 g; 0.02 mol, 0.13 eq.) andPOCl3 (128 g; 0.83 mol, 5.2 eq.) (a white suspension is formed). DIPEA (35 g, 0.27 mol, 1.69 eq.) is addedto the suspension dropwise in about 10 mm and then the reaction mixture is heated to 110-120° C. (clear solution). The reaction is monitored with HPEC until ratio 5-TFU:5-TFP<5 :95 (reactionnormally finished in 7-8 h; if reaction is not complete, additional P0C13 (5 g, 0.032 mol, 0.2 eq) and DIPEA (1.3 g, 0.01 mol, 0.06 eq) are charged and stirred for another 1-2 h). The reaction is then cooled tort and n-butyl acetate (80 mE) is added to the reaction mixture. About 60 mE of distillate (POC13 and some n-butyl acetate) is collected at 63-65° C./450-500 mbar. The resulting dark solution is slowly added to a mixture of conc. HC1 (165 g, 27 weight percent, 1.23 mol, 7.7 eq.) and methyl tertiary butyl ether (MTBE, 120 mE) while the temperature is maintained below 20° C. The organic phase is separated and the aqueous phase is extracted with MTBE (2x120 mE). The organic phase is gathered, washed with water until the pH value reaches ca. 5-6. MTBE is removed under reduced pressure (.-42° C./200 mbar), the final product is purified through distillation (87- 89° C./55 mbar) to afford 5-TFP as colorless oil (25.3 g, yield72.9percent; purity 98percent).2,4-dichloro-5-trifluoromethylpyrimidine (5-TFP)10061] Colorless to light yellow oil10062] ‘H NMR (CD3COCD3): ö 8.8 (s, 1 H),10063] ‘9F NMR (CD3COCD3): ö —63.710064] ESI MS (m/z) 216 [M—1]
72.9% at 110 - 120℃; To a jacket reactor (500 mL) is added 5-trifluoromethyluracil (5-TFU, 40 g, ~ 70 percent assay, ~ 0.16 mol, 1 .0 eq.), H3PO4 (2.4 g; 0.02 mol, 0.13 eq.) and POCI3 (128 g; 0.83 mol, 5.2 eq.) (a white suspension is formed). DIPEA (35 g, 0.27 mol, 1 .69 eq.) is added to the suspension dropwise in about 10 min and then the reaction mixture is heated to 1 10-120 °C (clear solution). The reaction is monitored with HPLC until ratio 5-TFU:5-TFP < 5:95 (reaction normally finished in 7-8 h; if reaction is not complete, additional POCI3 (5 g, 0.032 mol, 0.2 eq) and DIPEA (1 .3 g, 0.01 mol, 0.06 eq) are charged and stirred for another 1 -2 h). The reaction is then cooled to rt and n-butyl acetate (80 mL) is added to the reaction mixture. About 60 mL of distillate (POCI3 and some n-butyl acetate) is collected at 63-65 °C/450-500 mbar. The resulting dark solution is slowly added to a mixture of cone. HCI (165 g, 27 weight percent, 1 .23 mol, 7.7 eq.) and methyl tertiary butyl ether (MTBE, 120 mL) while the temperature is maintained below 20 °C. The organic phase is separated and the aqueous phase is extracted with MTBE (2 x 120 mL). The organic phase is gathered, washed with water until the pH value reaches ca. 5-6. MTBE is removed under reduced pressure (~ 42 °C/200 mbar), the final product is purified through distillation (87-89 °C/55 mbar) to afford 5-TFP as colorless oil (25.3 g, yield 72.9 percent; purity 98 percent). 2,4-dichloro-5-trifluoromethylpyrimidine (5-TFP) Colorless to light yellow oil 1H NMR (CD3COCD3): δ 8.8 (s, 1 H), 19F NMR (CD3COCD3): δ -63.7 ESI MS (m/z) 216 [M-1 ]"
61% at 25 - 90℃; for 5.16667 - 6.16667 h; 48 g (267 mmol) 5-trifluoromethyluracil is suspended in 210 mL phosphorus oxychloride (POCl3) while moisture is excluded. 47.7 g (320 mmol, 1.2 eq) diethylaniline is slowly added dropwise to this suspension, such that the temperature remains between 25° C. and 30° C. After the addition has ended the mixture is stirred for another 5-10 min in the water bath and the mixture is heated for 5-6 h at 80-90° C. while moisture is excluded. The excess POCl3 is destroyed by stirring-into about 1200 g sulphuric acid containing ice water and the aqueous phase is immediately extracted 3.x. with in each case 500 ml ether or t-butyl-methyl-ether. The combined ethereal extracts are washed 2.x. with 300 mL sulphuric acid-containing ice water (about 0.1 M) and with cold saline solution and immediately dried on sodium sulphate. The drying agent is filtered off and the solvent is eliminated in vacuo. The residue is distilled in vacuo (10 mbar) through a short column (20 cm) (head temperature: 65-70° C.), to obtain 35.3 g (0.163 mol, 61percent) of a colourless liquid which is poured off and stored under argon. DC: Rf=0.83 (cHex:EE=3:1)
17.7% at 85 - 100℃; for 36 h; Inert atmosphere 5- (trifluoromethyl) pyrimidine -2,2- (1H, 3H) - dione (18g, 0.1mol) was added to a 250ml three-necked flask, was added phosphorus oxychloride (45.8ml, 5eq), phosphoric acid (O.leq) under nitrogen, was heated in an oil bath, was slowly added dropwise diisopropylethyl amine (16ml) between 85 ~ 90 , temperature was raised to 100 dropwise completed reaction was refluxed 36h, evaporated to dryness under reduced pressure The solvent, i.e. by column chromatography an oily liquid 2,4-dichloro-5- (trifluoromethyl) pyrimidine (3.8 g of, yield 17.7percent).

Reference: [1] Patent: US2005/256145, 2005, A1, . Location in patent: Page/Page column 43
[2] Patent: US2005/256125, 2005, A1, . Location in patent: Page/Page column 29
[3] Patent: US2005/256144, 2005, A1, . Location in patent: Page/Page column 20
[4] Patent: US2014/135497, 2014, A1, . Location in patent: Paragraph 0060; 0061; 0062; 0063; 0064
[5] Patent: WO2014/76085, 2014, A1, . Location in patent: Page/Page column 9-10
[6] Patent: US2007/32514, 2007, A1, . Location in patent: Page/Page column 10
[7] Patent: CN105461695, 2016, A, . Location in patent: Paragraph 0136; 0137
[8] Patent: WO2004/48343, 2004, A1, . Location in patent: Page 74
[9] Patent: WO2008/77885, 2008, A2, . Location in patent: Page/Page column 13
[10] Patent: WO2009/63240, 2009, A1, . Location in patent: Page/Page column 43-44
[11] Patent: US2009/163467, 2009, A1, . Location in patent: Page/Page column 8
[12] Patent: WO2009/71535, 2009, A1, . Location in patent: Page/Page column 22-23
[13] Patent: WO2010/55117, 2010, A1, . Location in patent: Page/Page column 29
[14] Patent: WO2010/106097, 2010, A1, . Location in patent: Page/Page column 29-30
[15] Patent: WO2010/136559, 2010, A1, . Location in patent: Page/Page column 34
[16] Patent: US2011/33441, 2011, A1, . Location in patent: Page/Page column 8
[17] Journal of Fluorine Chemistry, 2015, vol. 179, p. 150 - 158
  • 2
  • [ 2314-97-8 ]
  • [ 66-22-8 ]
  • [ 54-20-6 ]
YieldReaction ConditionsOperation in experiment
93% With iron(III) sulfate; dihydrogen peroxide In water; dimethyl sulfoxide at 40 - 50℃; for 0.333333 h; 0.11 g (1.0 mmol) of uracil was 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:
2.0 ml of a 1N dimethyl sulfoxide solution, 1.0 ml of a 2.1 mol/l dimethyl sulfoxide solution of trifluoromethyl iodide, 0.2 ml of a 30percent hydrogen peroxide aqueous solution and 0.3 ml of a 1.0 mol/l aqueous solution of ferric sulfate.
The mixture was stirred at 40 to 50°C for 20 minutes and then the resulting solution was cooled to room temperature.
Formation of 5-trifluoromethyl uracil (19F-NMR yield: 94percent) was confirmed by 19F-NMR with 2,2,2-trifluoroethanol as an internal standard.
5-Trifluoromethyluracil was obtained as a white solid (0.17 g, yield: 93percent) by preparative thin-layer chromatography. 1H-NMR (deuterated acetone): δ8.09(s, 1H), 10.5(brs, 2H).
13C-NMR (deuterated acetone): δ104. 0 (q, JCF=32.4Hz), 123.6(q, JCF=268.2Hz), 144.2 (q, JCF=5. 9Hz), 150. 9, 160.2. 19F-NMR (deuterated acetone): δ-64.1.
MS (m/z): 180 [M]+.; EXAMPLE 9 Formation of 5-trifluoromethyluracil (19F-NMR yield: 76percent) was confirmed exactly in the same manner as in Example 1, except that the reaction was carried out in the atmosphere of air without the replacement with argon.
87% With sulfuric acid; dihydrogen peroxide; iron(II) sulfate; dimethyl sulfoxide In water at 40 - 50℃; for 0.333333 h; 0.055 g (0.5 mmol) of uracil was weighed and placed in a two-neck flask and the atmosphere in the flask was replaced with argon. The following materials were added thereinto: 1.0 ml of a 1 N dimethyl sulfoxide solution of sulfuric acid, 0.5 ml of a 2.1 mol/l dimethyl sulfoxide solution of trifluoromethyl iodide, 0.1 ml of a 30percent hydrogen peroxide aqueous solution and 0.15 ml of a 1.0 mol/l aqueous solution of iron(II) sulfate, and the mixture was stirred for 20 minutes. During the stirring, the temperature of the reaction system rose up in the range of from 40°C to 50°C. Thereafter, the resulting solution was cooled to room temperature. Formation of 5-trifluoromethyluracil (19F-NMR yield: 90percent) was confirmed by 19F-NMR with 2,2,2-trifluoroethanol as an internal standard. 5-trifluoromethyluracil was obtained as a white solid (0.16 g, yield: 87percent) in the same manner as in Example 1. 1H-NMR (deuterated acetone):δ8. 09(s, 1H), 10. 5 (brs, 2H). 13C-NMR(deuterated acetone):δ104. 0(q, JCF=32. 4Hz), 123. 6 (q, JCF=268. 2Hz), 144. 2(q, JCF=5. 9Hz), 150. 9, 160. 2. 19F-NMR(deuterated acetone):δ-64. 1. MS (m/z):180[M]+.
81% With caesium carbonate In dimethyl sulfoxide for 12 h; Inert atmosphere; Irradiation In a 25 mL reaction tube,Add Cs2CO3 (0.8 mmol),Compound A-1 (0.4 mmol, 1 equivalent),After replacing argon three times, add 1 mL of dimethyl sulfoxide (DMSO).100 μL (1.2 mmol) of Compound B in DMSO was injected.After stirring for 12 hours under blue light,Compound C-1,The yield was 81percent.
94 %Spectr. With tetrafluoroboric acid; iron(III) tetrafluoroborate; dihydrogen peroxide In water; dimethyl sulfoxide at 40 - 50℃; for 0.333333 h; 0.11 g (1.0 mmol) of uracil was 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: 0.21 ml of a 42percent tetrafluoroboric acid aqueous solution, 2.0 ml of dimethyl sulfoxide, 3.0 ml of a 2.0 mol/l dimethyl sulfoxide solution of trifluoromethyl iodide, 0.3 ml of a 1.0 mol/l aqueous solution of ferric tetrafluoroborate and 0.2 ml of a 30percent hydrogen peroxide aqueous solution. The mixture was stirred at 40 to 50°C for 20 minutes and then the resulting solution was cooled to room temperature. Formation of 5-trifluoromethyluracil (19F-NMR yield: 94percent) was confirmed in the same manner as in Example 1.
0.5 %Spectr. With iron(III) sulfate; sulfuric acid; dihydrogen peroxide In 1,1'-sulfinylbisbenzene; water at 40 - 50℃; for 0.333333 h; 0.11 g (1.0 mmol) of uracil was weighed and placed in a 50 ml two-neck flask equipped with a magnetic rotor and the atmosphere in the flask was replaced with trifluoromethyl iodide.
The following materials were added thereinto:
5.0 g of diphenyl sulfoxide, 0.053 ml of concentrated sulfuric acid, 0.2 ml of a 30percent hydrogen peroxide aqueous solution and 0.3 ml of a 1.0 mol/l aqueous solution of ferric sulfate.
The mixture was stirred at 40 to 50°C for 20 minutes and then the resulting solution was cooled to room temperature.
Formation of 5-trifluoromethyluracil (19F-NMR yield: 0.5percent) was confirmed by 19F-NMR with 2,2,2-trifluoroethanol as an internal standard.
94 - 97 %Spectr. With iron(III) sulfate; sulfuric acid; dihydrogen peroxide In water; dimethyl sulfoxide at 40 - 70℃; for 0.166667 - 1.66667 h; 1.1 g (10 mmol) of uracil was weighed and placed in a 100 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: 20 ml of a 1N dimethyl sulfoxide solution of sulfuric acid, 22.5 ml of dimethyl sulfoxide, 7.5 ml of a 2.0 mol/l dimethyl sulfoxide solution of trifluoromethyl iodide, 2.0 ml of a 30percent hydrogen peroxide aqueous solution and 3.0 ml of a 1.0 mol/l aqueous solution of ferric sulfate. The mixture was stirred at 40 to 50°C for 30 minutes and then the resulting solution was cooled to room temperature. Formation of 5-trifluoromethyluracil (19F-NMR yield: 94percent) was confirmed in the same manner as in Example 1.; EXAMPLE 11 1.1 g (10 mmol) of uracil was weighed and placed in a 100 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: 0.055 ml of concentrated sulfuric acid, 9 ml of dimethyl sulfoxide, 24.5 mmol of trifluoromethyl iodide, 2.0 ml of a 30percent hydrogen peroxide aqueous solution and 1.5 ml of a 1.0 mol/l aqueous solution of ferric sulfate. The mixture was stirred at 60 to 70°C for 10 minutes and then the resulting solution was cooled to room temperature. Formation of 5-trifluoromethyluracil (19F-NMR yield: 97percent) was confirmed in the same manner as in Example 1.; EXAMPLE 12 11.2 g (100 mmol) of uracil was weighed and placed in a 300 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: 80 ml of dimethyl sulfoxide, 0.55 ml of concentrated sulfuric acid, 245 mmol of trifluoromethyl iodide, 20 ml of a 30percent hydrogen peroxide aqueous solution and 10 ml of a 1.5 mol/l aqueous solution of ferric sulfate. The mixture was stirred at 60 to 70°C for 100 minutes and then the resulting solution was cooled to room temperature. Formation of 5-trifluoromethyluracil (19F-NMR yield: 97percent) was confirmed in the same manner as in Example 1.
0.2 %Spectr. With iron(III) sulfate; sulfuric acid; dihydrogen peroxide In butyl sulfoxide; water at 40 - 50℃; for 0.333333 h; 0.11 g (1.0 mmol) of uracil was weighed and placed in a 50 ml two-neck flask equipped with a magnetic rotor and the atmosphere in the flask was replaced with trifluoromethyl iodide.
The following materials were added thereinto:
5.0 ml of dibutyl sulfoxide, 0.053 ml of concentrated sulfuric acid, 0.2 ml of a 30percent hydrogen peroxide aqueous solution and 0.3 ml of a 1.0 mol/l aqueous solution of ferric sulfate.
The mixture was stirred at 40 to 50°C for 20 minutes and then the resulting solution was cooled to room temperature.
Formation of 5-trifluoromethyluracil (19F-NMR yield: 0.2percent) was confirmed by 19F-NMR with 2,2,2-trifluoroethanol as an internal standard.
70 %Spectr. With iron(III) sulfate; sulfuric acid; urea hydrogen peroxide adduct In water; dimethyl sulfoxide at 40 - 50℃; for 0.333333 h; 0.11 g (1.0 mmol) of uracil was 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: 2.0 ml of a 1N dimethyl sulfoxide solution of sulfuric acid, 3.0 ml of a 2.0 mol/l dimethyl sulfoxide solution of trifluoromethyl iodide, 0.12 g of hydrogen peroxide-urea composite and 0.3 ml of a 1 mol/l aqueous solution of ferric sulfate. The mixture was stirred at 40 to 50°C for 20 minutes and then the resulting solution was cooled to room temperature. Formation of 5-trifluoromethyl uracil (19F-NMR yield: 70percent) was confirmed in the same manner as in Example 1

Reference: [1] Patent: EP1947092, 2008, A1, . Location in patent: Page/Page column 36; 37
[2] Patent: EP2080744, 2009, A1, . Location in patent: Page/Page column 6
[3] Patent: CN108484508, 2018, A, . Location in patent: Paragraph 0023; 0026; 0029; 0032; 0033; 0034; 0035; 0038
[4] Patent: EP1947092, 2008, A1, . Location in patent: Page/Page column 37
[5] Patent: EP1947092, 2008, A1, . Location in patent: Page/Page column 37
[6] Patent: EP1947092, 2008, A1, . Location in patent: Page/Page column 38
[7] Patent: EP1947092, 2008, A1, . Location in patent: Page/Page column 37
[8] Patent: EP1947092, 2008, A1, . Location in patent: Page/Page column 37
  • 3
  • [ 66-22-8 ]
  • [ 54-20-6 ]
YieldReaction ConditionsOperation in experiment
57% at 90℃; for 24 h; Inert atmosphere; Sealed tube [00234] Uracil (28.0 mg, 0.250 mmol, 1.00 eq), K2S208 (270 mg, 1.00 mmol, 4.00 eq) and Cu(OAc)2 FontWeight="Bold" FontSize="10" H20 (100 mg, 0.500 mmol, 2.00 eq) were dissolved in glacial acetic acid (2.00 mL). TMG'CF3I (0.100 mL, 0.500 mmol, 2.00 eq) was added, the reaction vessel was sealed and heated at 90 °C for 24 hours. The reaction mixture was diluted with water (50 mL) and the resulting mixture extracted with ethyl acetate (3 x 25 mL). The combined ethyl acetate extracts were dried (MgS04) and concentrated in vacuo. The residue was purified by chromatography on silica gel eluting with 5percent MeOH/CH2Cl2 to afford 25.5 mg (0.142 mmol, 57percent) 12 as a white solid. [00235] R/ = 0.30 (5percent MeOH/CH2Cl2). NMR spectroscopy: 1H NMR (400 MHz, CD30D, 23 °C) δ ppm 7.93 (s, 1H), 4.60 (bs, 2H). 13C NMR (125 MHz, CD3OD, 23 °C) δ ppm 162.1, 152.5, 144.8 (q, JCF = 6 Hz), 123.9 (q, J = 269 Hz), 104.8 (q, JCF = 34 Hz). 19F NMR (376 MHz, CD3OD, 23 °C) δ ppm -64.8. Mass spectrometry: HRMS (APCI) (m/z): Calcd for [C5H3F3N202]+, [M ] : 180.0147. Found, 180.0157.
Reference: [1] Angewandte Chemie - International Edition, 2015, vol. 54, # 12, p. 3712 - 3716[2] Angew. Chem., 2015, vol. 127, # 12, p. 3783 - 3787,5
[3] Patent: WO2015/168368, 2015, A1, . Location in patent: Paragraph 00234; 00235
  • 4
  • [ 153600-17-0 ]
  • [ 54-20-6 ]
Reference: [1] Journal of Fluorine Chemistry, 1996, vol. 77, # 1, p. 93 - 95
[2] Patent: US5352787, 1994, A,
[3] Patent: US5352787, 1994, A,
  • 5
  • [ 2145-56-4 ]
  • [ 54-20-6 ]
YieldReaction ConditionsOperation in experiment
88% With sulfuric acid; iodine In water; dimethyl sulfoxide Example 1
Synthesis of 5-trifluoromethyluracil
In 88.7 ml of dimethylsulfoxide, 25.2 g of 5-trifluoromethyl-5,6-dihydrouracil was dissolved and 3.47 g of iodine and 0.76 ml of concentrated sulfuric acid were added to the solution to obtain a uniform solution.
The obtained solution was stirred at 140oC for 6 hours, and then cooled to room temperature, followed by adding 150 g of 3percent aqueous sodium sulfite solution to reduce iodine.
The resulting mixture was concentrated under reduced pressure.
After adding water to the residue, the residue was extracted three times with ethyl acetate.
The ethyl acetate layer was concentrated and the residue was recrystallized from 100 ml of water to obtain 21.9 g (88percent) of 5-trifluoromethyluracil as white needle-shaped crystals.
m.p.: 239 - 241oC
NMR: identical to that reported in references
73% With sulfuric acid; iodine In <i>N</i>-methyl-acetamide; water; dimethyl sulfoxide Example 2
Synthesis of 5-trifluoromethyluracil
In 24.7 ml of dimethylformamide, 10 g of 5-trifluoromethyl-5,6-dihydrouracil is dissolved, and 12.8 g of dimethylsulfoxide, 1.4 g of iodine and 0.54 g of concentrated sulfuric acid were added to obtain a uniform solution.
The obtained solution was stirred at 117oC for 9 hours.
The resultant was cooled to room temperature and 70 g of 3percent aqueous sodium sulfite was added to reduce iodine.
The resulting mixture was concentrated under reduced pressure.
Water was added to the residue and the residue was extracted three times with ethyl acetate.
The ethyl acetate layer was concentrated and the residue was recrystallized from 40 ml of water to obtain 7.2 g (73percent) of 5-trifluoromethyluracil in the form of white needle-shaped crystals.
Reference: [1] Patent: EP635517, 1995, A1,
[2] Patent: EP635517, 1995, A1,
[3] Patent: EP635517, 1995, A1,
[4] Patent: EP635517, 1995, A1,
  • 6
  • [ 2145-56-4 ]
  • [ 54-20-6 ]
Reference: [1] Chemistry Letters, 1984, p. 1595 - 1598
[2] Tetrahedron Letters, 1982, vol. 23, # 40, p. 4099 - 4100
  • 7
  • [ 39971-65-8 ]
  • [ 66-22-8 ]
  • [ 54-20-6 ]
Reference: [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 44, p. 11868 - 11871[2] Angew. Chem., 2014, vol. 126, # 44, p. 12062 - 12065,4
  • 8
  • [ 116393-64-7 ]
  • [ 54-20-6 ]
Reference: [1] Synthetic Communications, 1988, vol. 18, # 2, p. 213 - 220
  • 9
  • [ 66-22-8 ]
  • [ 54-20-6 ]
YieldReaction ConditionsOperation in experiment
32 %Spectr. With sulfuric acid; dihydrogen peroxide; iron In water; dimethyl sulfoxide at 40 - 50℃; for 0.333333 h; 0.11 g (1.0 mmol) of uracil and 0.028 g (0.5 mmol) of iron powder 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: 2.0 ml of dimethyl sulfoxide, 2.0 ml of a 1N dimethyl sulfoxide solution of sulfuric acid, 1.0 ml of a 3.0 mol/l dimethyl sulfoxide solution of trifluoromethyl iodide and 0.2 ml of a 30percent hydrogen peroxide aqueous solution. The mixture was stirred at 40 to 50°C for 20 minutes and then the resulting solution was cooled to room temperature. Formation of 5-trifluoromethyluracil (19F-NMR yield: 32percent) was confirmed in the same manner as in Example 1.
Reference: [1] Patent: EP1947092, 2008, A1, . Location in patent: Page/Page column 37
  • 10
  • [ 371-76-6 ]
  • [ 66-22-8 ]
  • [ 54-20-6 ]
Reference: [1] Journal fuer Praktische Chemie (Leipzig), 1984, vol. 326, # 6, p. 985 - 993
  • 11
  • [ 2145-56-4 ]
  • [ 707-04-0 ]
  • [ 54-20-6 ]
Reference: [1] Chemistry Letters, 1984, p. 1595 - 1598
  • 12
  • [ 7057-43-4 ]
  • [ 54-20-6 ]
Reference: [1] Journal of Fluorine Chemistry, 1993, vol. 63, # 1-2, p. 43 - 52
  • 13
  • [ 197515-85-8 ]
  • [ 57-13-6 ]
  • [ 54-20-6 ]
Reference: [1] Russian Chemical Bulletin, 1998, vol. 47, # 6, p. 1232 - 1233
  • 14
  • [ 75-63-8 ]
  • [ 66-22-8 ]
  • [ 54-20-6 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 1988, vol. 61, p. 3531 - 3538
  • 15
  • [ 66-22-8 ]
  • [ 407-25-0 ]
  • [ 54-20-6 ]
Reference: [1] Journal fuer Praktische Chemie (Leipzig), 1984, vol. 326, # 6, p. 985 - 993
  • 16
  • [ 1780-31-0 ]
  • [ 54-20-6 ]
Reference: [1] Journal of Fluorine Chemistry, 1996, vol. 77, # 1, p. 93 - 95
  • 17
  • [ 65-71-4 ]
  • [ 54-20-6 ]
Reference: [1] Journal of Fluorine Chemistry, 1996, vol. 77, # 1, p. 93 - 95
  • 18
  • [ 153600-16-9 ]
  • [ 54-20-6 ]
Reference: [1] Journal of Fluorine Chemistry, 1996, vol. 77, # 1, p. 93 - 95
  • 19
  • [ 54-20-6 ]
  • [ 939791-38-5 ]
Reference: [1] Patent: US2011/33441, 2011, A1,
  • 20
  • [ 54-20-6 ]
  • [ 1374640-70-6 ]
Reference: [1] Patent: US2018/230133, 2018, A1,
[2] Patent: US2018/230133, 2018, A1,
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