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[ CAS No. 53135-24-3 ]

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2D
Chemical Structure| 53135-24-3
Chemical Structure| 53135-24-3
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Product Details of [ 53135-24-3 ]

CAS No. :53135-24-3MDL No. :MFCD00223606
Formula : C8H10N2O3 Boiling Point : 267.9°C at 760 mmHg
Linear Structure Formula :-InChI Key :N/A
M.W :182.18Pubchem ID :293750
Synonyms :

Computed Properties of [ 53135-24-3 ]

TPSA : 67.8 H-Bond Acceptor Count : 4
XLogP3 : -0.3 H-Bond Donor Count : 1
SP3 : 0.38 Rotatable Bond Count : 3

Safety of [ 53135-24-3 ]

Signal Word:WarningClass:N/A
Precautionary Statements:P261-P305+P351+P338UN#:N/A
Hazard Statements:H315-H319-H335Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 53135-24-3 ]

  • Upstream synthesis route of [ 53135-24-3 ]
  • Downstream synthetic route of [ 53135-24-3 ]

[ 53135-24-3 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 53135-24-3 ]
  • [ 5472-46-8 ]
Reference: [1] Journal of the Chemical Society, 1937, p. 367[2] Journal of the Chemical Society, 1938, p. 28
  • 2
  • [ 53135-24-3 ]
  • [ 2134-36-3 ]
YieldReaction ConditionsOperation in experiment
57.7% for 0.5 h; Reflux ethyl 4-chloro-2-methylpyrimidine-5-carboxylate
Phosphorus oxychloride (50 mL, 23.33 mmol) was added to ethyl 2-methyl-6-oxo-1,6-dihydropyrimidine-5-carboxylate (Intermediate 174, 4.25 g, 23.33 mmol).
The insoluble mixture was refluxed for 30 minutes.
The product was soluble in POCl3 where as the starting material was not.
The excess POCl3 was removed under vacuum.
The mixture was evaporated to dryness and redissolved in EtOAc (100 mL), and washed sequentially with water (75 mL) and saturated brine (75 mL).
The organic layer was dried over MgSO4, filtered and evaporated to afford crude product.
The crude product was purified by flash silica chromatography, elution gradient 10 to 30percent EtOAc in isohexane.
Pure fractions were evaporated to dryness to afford ethyl 4-chloro-2-methylpyrimidine-5-carboxylate (2.70 g, 57.7percent) as a colourless oil.
1H NMR (400.132 MHz, CDCl3) δ 1.42 (3H, t), 2.78 (3H, s), 4.44 (2H, q), 9.05 (1H, s)
m/z (ESI+) (M+H)+=201; HPLC tR=2.17 min.
Reference: [1] Patent: US2009/264401, 2009, A1, . Location in patent: Page/Page column 117-118
[2] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 25, p. 435
[3] Shionogi Kenkyusho Nenpo, 1952, # 2, p. 76,78[4] Chem.Abstr., 1957, p. 10008
[5] Journal of the Chemical Society, 1937, p. 367[6] Journal of the Chemical Society, 1938, p. 28
[7] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 21, p. 6756 - 6761
[8] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 25, p. 435,437
  • 3
  • [ 53135-24-3 ]
  • [ 2134-36-3 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 15, p. 1645 - 1648
[2] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 22, p. 5771 - 5780
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  • [ 124-42-5 ]
  • [ 87-13-8 ]
  • [ 53135-24-3 ]
YieldReaction ConditionsOperation in experiment
61%
Stage #1: at 0℃; for 0.333333 h;
Stage #2: at 0℃; for 0.5 h;
Stage #3: With triethylamine In ethanol for 2 h; Reflux
(0294) To a solution of sodium (2.90 g, 126 mmol) in ethanol (150 mL) was added acetoamidine hydrochloride (11.9 g, 126 mmol) at 0° C. The mixture was stirred at 0° C. for 20 minutes, diethyl (ethoxymethylene)malonate (28.6 g, 132 mmol) was added dropwise thereto, the mixture was stirred at 0° C. for 30 minutes, and triethylamine (20 mL, 145 mmol) was added thereto. The mixture was heated under reflux for 2 hours, the reaction mixture was concentrated, water (400 mL) was added thereto, citric acid was added to adjust pH to 4 to 5, and the mixture was extracted with dichloromethane (200 mL) three times. The organic layers were combined, dried over anhydrous sodium sulfate, filtrated, and concentrated. To the resulting concentrated residue was added tert-butyl methyl ether (200 mL), and the precipitate was collected on a filter to give the title compound (14.0 g, 61percent) (0295) 1H-NMR (400 MHz, CDCl3) δ: 1.40 (3H, t, J=7.2 Hz), 2.61 (3H, s), 4.39 (2H, q, J=7.2 Hz), 8.73 (1H, s).
27% With hydrogenchloride In ethanol; dichloromethane; sodium ethanolate; ethyl acetate EXAMPLE 30
Ethyl 2-methyl-pyrimidin-6(1H)-one-5-carboxylate STR55
Acetamidine hydrochloride (37.16 g, 0.39 mole) was stirred in sodium ethoxide in ethanol (73 mL of a 21percent solution, 0.20 mole) for 5 minutes.
Diethyl ethoxymethylenemalonate (31.5 mL, 0.15 mole) was added, and the reaction mixture was refluxed for 5 hours.
The reaction mixture was allowed to cool to room temperature overnight, and diluted with dichloromethane (100 mL).
The solution was filtered, washing the solid cake with dichloromethane.
The filtrate was concentrated at reduced pressure.
The residue was dissolved in dichloromethane (150 mL) and 2.0N HCl (30 mL).
The pH of the aqueous layer was 1.
The organic layer was washed with water, saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure.
The residue was dissolved in hot dichloromethane (50 mL).
Ethyl acetate was added (50 mL).
The product precipitated.
The solution was boiled for 5 minutes, cooled to room temperature, and hexanes were added (50 mL).
The resulting crystals were filtered, then washed with ethyl acetate (20 mL) followed by hexanes (50 mL) to yield the title compound (7.22 g, 27percent) as off-white crystals. Rf =0.27 (silica gel, 10percent isopropanol in dichloromethane).
The title compound also was prepared by the route described in Example 102.
27% With hydrogenchloride In ethanol; dichloromethane; sodium ethanolate; ethyl acetate Example 30
Ethyl 2-methyl-pyrimidin-6(1H)-one-5-carboxylate STR57
Acetamidine hydrochloride (37.16 g, 0.39 mole) was stirred in sodium ethoxide in ethanol (73 mL of a 21percent solution, 0.20 mole) for 5 minutes.
Diethyl ethoxymethylenemalonate (31.5 mL, 0.15 mole) was added, and the reaction mixture was refluxed for 5 hours.
The reaction mixture was allowed to cool to room temperature overnight, and diluted with dichloromethane (100 mL).
The solution was filtered, washing the solid cake with dichloromethane.
The filtrate was concentrated at reduced pressure.
The residue was dissolved in dichloromethane (150 mL) and 2.0N HCl (30 mL).
The pH of the aqueous layer was 1.
The organic layer was washed with water, saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure.
The residue was dissolved in hot dichloromethane (50 mL).
Ethyl acetate was added (50 mL).
The product precipitated.
The solution was boiled for 5 minutes, cooled to room temperature, and hexanes were added (50 mL).
The resulting crystals were filtered, then washed with ethyl acetate (20 mL) followed by hexanes (50 mL) to yield the title compound (7.22 g, 27percent) as off-white crystals. Rf =0.27 (silica gel, 10percent isopropanol in dichloromethane).
The title compound also was prepared by the route described in Example 102.
27% With hydrogenchloride In ethanol; dichloromethane; sodium ethanolate; ethyl acetate Example 30
Ethyl 2-methyl-pyrimidin-6(1H)-one-5-carboxylate STR52
Acetamidine hydrochloride (37.16 g, 0.39 mole) was stirred in sodium ethoxide in ethanol (73 mL of a 21percent solution, 0.20 mole) for 5 minutes.
Diethyl ethoxymethylenemalonate (31.5 mL, 0.15 mole) was added, and the reaction mixture was refluxed for 5 hours.
The reaction mixture was allowed to cool to room temperature overnight, and diluted with dichloromethane (100 mL).
The solution was filtered, washing the solid cake with dichloromethane.
The filtrate was concentrated at reduced pressure.
The residue was dissolved in dichloromethane (150 mL) and 2.0N HCl (30 mL).
The pH of the aqueous layer was 1.
The organic layer was washed with water, saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure.
The residue was dissolved in hot dichloromethane (50 mL).
Ethyl acetate was added (50 mL).
The product precipitated.
The solution was boiled for 5 minutes, cooled to room temperature, and hexanes were added (50 mL).
The resulting crystals were filtered, then washed with ethyl acetate (20 mL) followed by hexanes (50 mL) to yield the title compound (7.22 g, 27percent) as off-white crystals. Rf =0.27 (silica gel, 10percent isopropanol in dichloromethane).
The title compound also was prepared by the route described in Example 102.
27% With hydrogenchloride In ethanol; dichloromethane; sodium ethanolate; ethyl acetate Example 30
Ethyl 2-Methyl-pyrimidin-6(1H)-one-5-carboxylate STR50
Acetamidine hydrochloride (37.16 g, 0.39 mole) was stirred in sodium ethoxide in ethanol (73 mL of a 21percent solution, 0.20 mole) for 5 minutes.
Diethyl ethoxymethylenemalonate (31.5 mL, 0.15 mole) was added, and the reaction mixture was refluxed for 5 hours.
The reaction mixture was allowed to cool to room temperature overnight, and diluted with dichloromethane (100 mL).
The solution was filtered, washing the solid cake with dichloromethane.
The filtrate was concentrated at reduced pressure.
The residue was dissolved in dichloromethane (150 mL) and 2.0N HCl (30 mL).
The pH of the aqueous layer was 1.
The organic layer was washed with water, saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure.
The residue was dissolved in hot dichloromethane (50 mL).
Ethyl acetate was added (50 mL).
The product precipitated.
The solution was boiled for 5 minutes, cooled to room temperature, and hexanes were added (50 mL).
The resulting crystals were filtered, then washed with ethyl acetate (20 mL) followed by hexanes (50 mL) to yield the title compound (7.22 g, 27percent) as off-white crystals. Rf =0.27 (silica gel, 10percent isopropanol in dichloromethane).
The title compound also was prepared by the route described in Example 102.
27% With sodium ethanolate In ethanol for 5 h; Heating / reflux
Acetamidine hydrochloride (37.16 g, 0.39 mole) was stirred in sodium ethoxide in ethanol (73 ML of a 21percent solution, 0.20 mole) for 5 minutes..
diethyl ethoxymethylenemalonate (31.5 ML, 0.15 mole) was added, and the reaction mixture was refluxed for 5 hours..
The reaction mixture was allowed to cool to room temperature overnight, and diluted with dichloromethane (100 ML)..
The solution was filtered, washing the solid cake with dichloromethane..
The filtrate was concentrated at reduced pressure..
The residue was dissolved in dichloromethane (150 ML) and 2.0N HCl (30 ML)..
The PH of the aqueous layer was 1..
The organic layer was washed with water, saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure..
The residue was dissolved in hot dichloromethane (50 ML)..
ethyl acetate was added (50 ML)..
The product precipitated..
The solution was boiled for 5 minutes, cooled to room temperature, and hexanes were added (50 ML)..
The resulting crystals were filtered, then washed with ethyl acetate (20 ML) followed by hexanes (50 ML) to yield the title compound (7.22 g, 27percent) as off-white crystals. Rf=0.27 (silica gel, 10percent isopropanol in dichloromethane)..
The title compound also was prepared by the route described in Example 102.

Reference: [1] Patent: US2016/122319, 2016, A1, . Location in patent: Paragraph 0293-0295
[2] Patent: US6008351, 1999, A,
[3] Patent: US6011158, 2000, A,
[4] Patent: US5656645, 1997, A,
[5] Patent: US5658930, 1997, A,
[6] Patent: US6342504, 2002, B1, . Location in patent: Page column 58
[7] Journal of Organic Chemistry, 1946, vol. 11, p. 741,749
[8] Journal of the Chemical Society, 1937, p. 367[9] Journal of the Chemical Society, 1938, p. 28
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  • [ 87-13-8 ]
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YieldReaction ConditionsOperation in experiment
61%
Stage #1: With sodium In ethanol at 0℃; for 0.333333 h;
Stage #2: With triethylamine In ethanol at 0℃; for 2.5 h; Reflux
Sodium (2.90g, 126mmol) and acetamidine hydrochloride (11.9g, 126mmol) in ethanol solution (150mL), it was added at 0°C. After stirring for 20 minutes at 0°C, Ethoxymethylene diethyl malonate (28.6g, 132mmol) It was added dropwise triethylamine (20mL, 145mmol) and stirred for 30 minutes at 0°C. After heated to reflux for 2 hours, The reaction mixture was concentrated, after addition of water (400 mL), citric acid is added to adjust to pH4 ~ 5, and extracted 3 times with dichloromethane (200 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting concentrated residue tert- butyl methyl ether (200 mL) was added, the precipitate By collected by filtration to give the title compound (14.0g, 61percent).
49.5% With sodium ethanolate In ethanol at 20 - 60℃; for 6.0833 h; Inert atmosphere ethyl 2-methyl-6-oxo-1,6-dihydropyrimidine-5-carboxylate
diethyl 2-(ethoxymethylene)malonate (9.35 mL, 46.25 mmol) was added dropwise to acetimidamide hydrochloride (4.37 g, 46.25 mmol), and sodium ethoxide (17.27 mL, 46.25 mmol) in ethanol (50 mL) at room temperature over a period of 5 minutes under nitrogen.
The resulting solution was stirred at 60° C. for 6 hours.
The reaction mixture was evaporated to dryness and redissolved in EtOAc (50 mL).The precipitate was collected by filtration, washed with EtOH (10 mL) and dried under vacuum to afford ethyl 2-methyl-6-oxo-1,6-dihydropyrimidine-5-carboxylate (4.17 g, 49.5percent) as a cream solid, which was used without further purification.
1H NMR (400.13 MHz, DMSO-d6) δ 1.15-1.23 (3H, t), 2.21 (3H, s), 4.09-4.17 (2H, q), 8.31 (1H, s)
m/z (ESI+) (M+H)+=183; HPLC tR=0.78 min.
Reference: [1] Patent: JP2016/108326, 2016, A, . Location in patent: Paragraph 0224; 0225
[2] Patent: US2009/264401, 2009, A1, . Location in patent: Page/Page column 117
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  • [ 36896-17-0 ]
  • [ 87-13-8 ]
  • [ 53135-24-3 ]
YieldReaction ConditionsOperation in experiment
46% for 26.25 h; Heating / reflux
Acetamidine acetate (37.21 g, 0.31 mole) and diethyl ethoxymethylenemalonate (63 ML, 0.31 mole) were refluxed for 4 h in ethanol (60 ML)..
The reaction mixture was allowed to cool for 15 minutes, then acetamidine acetate (37.21 g, 0.31 mole) was added..
The reaction mixture was refluxed for 22 hours, allowed to cool to room temperature, and diluted with water (200 ML) and dichloromethane (200 ML)..
The aqueous layer was extracted with 10percent isopropanol/dichloromethane (2*200 ML)..
The combined organic extracts were washed with water (50 ML), brine (50 ML), dried over magnesium sulfate, filtered and the solvent was removed..
The residue was recrystallized from chloroform/hexanes in two crops to afford the title compound (24.92 g) in 46percent yield as yellowish crystals. Rf=0.27 (silica gel, 10percent isopropanol in dichloromethane); m.p. 187 to 188° C.
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 1997, vol. 7, # 12, p. 1543 - 1548
[2] Patent: US6008351, 1999, A,
[3] Patent: US6011158, 2000, A,
[4] Patent: US5656645, 1997, A,
[5] Patent: US5658930, 1997, A,
[6] Patent: US6342504, 2002, B1, . Location in patent: Page column 92
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  • [ 143-37-3 ]
  • [ 87-13-8 ]
  • [ 53135-24-3 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 3, p. 403 - 406
[2] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 21, p. 6756 - 6761
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  • [ 698-30-6 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1990, # 11, p. 2963 - 2966
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