[ CAS No. 5472-38-8 ] {[proInfo.proName]}

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Quality Control of [ 5472-38-8 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 5472-38-8 ]

Product Details of [ 5472-38-8 ]

CAS No. :	5472-38-8	MDL No. :	MFCD00056287
Formula :	C₉H₁₄O₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	202.20	Pubchem ID :	-
Synonyms :

Safety of [ 5472-38-8 ]

Signal Word:	Warning	Class:
Precautionary Statements:	P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501	UN#:
Hazard Statements:	H302-H315-H319-H335	Packing Group:
GHS Pictogram:

Application In Synthesis of [ 5472-38-8 ]

* 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 [ 5472-38-8 ]
Downstream synthetic route of [ 5472-38-8 ]

[ 5472-38-8 ] Synthesis Path-Upstream 1~6

1
[ 5472-38-8 ]
[ 867130-58-3 ]

Reference： [1] Journal of the American Chemical Society, 1955, vol. 77, p. 3376

2
[ 5472-38-8 ]
[ 4282-29-5 ]

Reference： [1] Journal of Organic Chemistry, 1954, vol. 19, p. 1671,1677

3
[ 5472-38-8 ]
[ 61727-34-2 ]

Reference： [1] Monatshefte fur Chemie, 2016, vol. 147, # 4, p. 767 - 773
[2] Patent: WO2016/22644, 2016, A1,
[3] Patent: WO2009/152027, 2009, A1,

4
[ 5472-38-8 ]
[ 6214-47-7 ]

Reference： [1] Patent: WO2012/110773, 2012, A1,
[2] Patent: WO2014/27199, 2014, A1,
[3] Monatshefte fur Chemie, 2016, vol. 147, # 4, p. 767 - 773

5
[ 3473-63-0 ]
[ 5472-38-8 ]
[ 6214-46-6 ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: With sodium ethanolate In ethanol at 0℃; for 0.0833333 h; Inert atmosphere Stage #2: at 0 - 20℃; for 48 h; Inert atmosphere Stage #3: With hydrogenchloride In ethanol; water at 20℃; for 0.5 h; Inert atmosphere	General procedure: A solution of sodium ethoxide in ethanol was cooled to0 C under argon atmosphere. Diethyl 2-formylsuccinatewas added under stirring. After 5 min, the correspondingamidine was added at 0 C and stirring was continued at rtfor 3 days. Aqueous hydrogen chloride solution (5 percent) wasadded and it was stirred for 30 min. After addition of waterthe ethanol was removed in vacuo at 30 C. The precipitatewas filtered off to give compound 1 (X = H, Me, Ph, SMe;Y = H, R1 = Et)

Reference： [1] Monatshefte fur Chemie, 2016, vol. 147, # 4, p. 767 - 773

6
[ 5472-38-8 ]
[ 124391-75-9 ]

Reference： [1] Patent: CN103709126, 2018, B,

[ 5472-38-8 ] Synthesis Path-Downstream 1~16

1
[ 3599-89-1 ]
[ 5472-38-8 ]
[ 90873-78-2 ]

Reference： [1]Patent: DE670095,1936,
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 25,p. 435,437

2
[ 109-94-4 ]
[ 123-25-1 ]
[ 5472-38-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium; In diethyl ether; at 40℃; for 5h;	To a suspension of sodium (333 mg, 14 mmol, 1.2 eq) in diethyl ether (7 mL) were added <strong>[123-25-1]succinic acid diethyl ester</strong> (2.1 g, 12 mmol, 1 eq) and formic acid ethyl ester (1.7 mL, 20 mmol, 1.7 eq). The mixture was stirred at 40 C. for 5 h. Water (10 mL) was added and the aqueous layer was washed with diethyl ether (2×10 mL). The aqueous layer was then acidified with a 6N solution of hydrochloric acid and extracted with diethyl ether (3×10 mL). The organic layers were dried over magnesium sulfate, filtered and evaporated in vacuo to afford the expected compound as orange oil (2.6 g, quant. yield).
100%	With sodium; In diethyl ether; at 40℃; for 5h;	To a suspension of sodium (333 mg, 14 mmol, 1.2 eq) in diethyl ether (7 mL) were added <strong>[123-25-1]succinic acid diethyl ester</strong> (2.1 g, 12 mmol, 1 eq) and formic acid ethyl ester (1.7 mL, 20 mmol, 1.7 eq). The mixture was stirred at 40 C. for 5 h. Water (10 mL) was added and the aqueous layer was washed with diethyl ether (2×10 mL). The aqueous layer was then acidified with a 6N solution of hydrochloric acid and extracted with diethyl ether (3×10 mL). The organic layers were dried over magnesium sulfate, filtered and evaporated in vacuo to afford the expected compound as orange oil (2.6 g, quant. yield).
95.1%	With sodium hydride; In toluene; at 20℃; for 16h;	Dry 10L four-neck flask, add 1800ml of toluene, 60% sodium hydride 200g, slightly hot stirring to disperse;Cool down to below 20C and add <strong>[123-25-1]diethyl succinate</strong> 871gAnd a mixture of ethyl formate 445g;After completion of the dropwise addition, the reaction mixture was stirred at room temperature for 16h until the material disappeared (GC monitoring).The reaction is completed, cooled to below 10 C, add ice water 2kg, stirring for 20min so that the basic full-solution, separation, toluene layer with water twice, each 300ml, combined water layer;The aqueous layer was adjusted to pH 3-4 with concentrated hydrochloric acid, stirred for 20 minutes until the pH was stable, the oil and water were separated, the aqueous layer was extracted three times with ethyl acetate, and the organic layers were combined and washed with saturated saline.The organic layer was dried under reduced pressure to recover ethyl acetate to give 960 g of a brownish-yellow transparent liquid with a yield of 95.1%.

54%		Diethyl 2-formylsuccinate; To a mixture of sodium (1.66 g, 72.13 mmol) in diethyl ether (35 mL) was added <strong>[123-25-1]diethyl succinate</strong> (10 mL, 60.11 mmol) and ethyl formate (8.25 mL, 102.18 mmol) at room temperature, and the reaction mixture was refluxed for 5 hours. After the cooling to room temperature, water was added to the mixture until the sodium salt was dissolved completely and aqueous layer was separated. The aqueous layer was neutralized by 6M hydrochloric acid (10.8 mL) and extracted with diethyl ether. The extracts were washed with sat. NaHC03, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by distillation (115- 120C, 10 mmHg) to give diethyl 2-formylsuccinate (6.55 g, 54%) as colorless oil.
53%		Intermediate 1; 5,5-dimethyl-7-[(1S' )-1-methylpropyI]-2-(methylsulfonyl)-5,7-dihydro-6H-pyrrolo[2,3- d] pyrimidin-6-one; Step 1 : Diethyl 2-formylsuccmate; Ethanol (27.0 g, 0.574 mol) was added dropwise to a suspension of sodium hydride (60 wt%, 23.0 g, 0.574 mol) in tetrahydrofuran (300 mL); the mixture was stirred at room temperature for 1 hour. Upon cooling to 10 C (cold water bath), solutions of <strong>[123-25-1]diethyl succinate</strong> (100 g, 0.574 mol) in tetrahydrofuran (100 mL) followed by ethyl formate (42.5 g, 0.574 mol) in tetrahydrofuran (100 mL) were added dropwise. After stirring for 16 h at room temperature, water (500 mL) was added and the resulting solution was washed with diethyl ether (2 x 250 mL). The water phase was acidified with 50% aq. H2SO4 and the resulting suspension was extracted with diethyl ether (2 x 250 mL). The combined organic layer was washed with water (3 x 200 mL), dried with sodium sulfate, filtrated through Celite, and concentrated under reduced pressure. The residue was distilled in vacuo (5 mm Hg) to afford 62.1 g (53% yield) of the desired diethyl 2-formylsuccinate, b.p. 90 C. <n="27"/>1H NMR (400 MHz, CDCl3) delta: 11.40 (d, J= 11.0 Hz, 0.5 H), 9.80 (s, 0.5 H), 7.00 (d, J= 11.0 Hz, 0.5 H), 4.30-4.00 (m, 4 H), 3.70-3.61 (m, 0.5 H), 3.00 (s, 1 H), 2.85-2.70 (m, 1 H), 1.28-1.10 (m, 6 H).
37%	With sodium; In diethyl ether; at 20℃; for 12h;Inert atmosphere;	15.1. ethyl 2-formylbutanedioate To a suspension of 1.32 g (57.41 mmol) of sodium in 35 mL of anhydrous Et2O is added dropwise, at 0 C., under argon, a mixture of 10 g (57.41 mmol) of ethyl butanedioate and 4.62 mL (57.41 mmol) of ethyl formate. The medium is then stirred for 12 hours at room temperature, taken up in 100 mL of water and extracted with 100 mL of Et2O. The aqueous phase is acidified to pH 5 and then extracted with 100 mL of Et2O. The organic phase is then dried over Na2SO4, filtered and then concentrated under reduced pressure. The residue obtained is purified by chromatography on a column of silica gel, eluting with a 7/3 cyclohexane/EtOAc mixture. 4.3 g of ethyl 2-formylbutanediaote are obtained in the form of a colourless oil. Yield: 37% 1H NMR, 1H NMR, CDCl3, 400 MHz, delta (ppm): 10.0 (s, 1H); 7.1 (d, 1H); 4.4-4.2 (m, 5H); 2.9 (dd, 2H); 1.3 (m, 6H);
	With sodium; In ethanol; water; toluene;	(i) diethyl (RS)-formylsuccinate Ethanol (20 cm3) was added portionwise to a suspension of finely divided sodium (10.0 g) in dry toluene (100 cm3). On completion of the addition the mixture was heated for 3.5 hours at 80 C. To the resulting yellow suspension, cooled to 20 C., was added dropwise, over a period of 1 hour, a mixture of <strong>[123-25-1]diethyl succinate</strong> (70.0 g) and ethyl formate (35.0 g), whilst the temperature of the mixture was maintained in the range 20 to 30 C. The mixture was kept at the ambient temperature for 16 hours after which water (100 cm3) was added carefully. The aqueous layer was separated, neutralised with 50% aqueous sulphuric acid, and extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate, and concentrated by evaporation of the solvent under reduced pressure. The residual liquid (66 g) was subjected to fractional distillation under reduced pressure to obtain the desired diethyl (RS)-formylsuccinate (46.0 g), boiling range 82 to 86 C./0.53 mmHg. NMR spectroscopy indicated that the product exists as an approximately 1:1 mixture of keto and enol forms. 1 H NMR (CDCl3): 1.10-1.40 (m,3H) 2.90 (d, J=7Hz, 1H); 3.05 (s,1H); 3.75 (t, J=7 Hz, 0.5H); 4.00-4.40 (m,4H); 7.10 (d,J=11 Hz, 0.5H); 9.92 (s, 0.5 H); 11.5 (d, J=11 Hz, 0.5H).
	With sodium; In ethanol; water; toluene;	EXAMPLE 2 The Example illustrates the preparation of diethyl (RS)-formylsuccinate. Ethanol (20 cm3) was added portionwise to a suspension of finely divided sodium (10.0 g) in dry toluene (100 cm3). On completion of the addition the mixture was heated for 3.5 hours at 80 C. To the resulting yellow suspension, cooled to 20 C., was added dropwise, over a period of 1 hour, a mixture of <strong>[123-25-1]diethyl succinate</strong> (70.0 g) and ethyl formate (35.0 g), whilst the temperature of the mixture was maintained in the range 20 to 30 C. The mixture was kept at the ambient temperature for 16 hours after which water (100 cm3) was added carefully. The aqueous layer was separated, neutralised with 50% aqueous sulphuric acid, and extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate, and concentrated by evaporation of the solvent under reduced pressure. The residual liquid (66 g) was subjected to fractional distillation under reduced pressure to obtain the desired diethyl (RS)-formylsuccinate (46.0 g), boiling range 82 to 86 C./0.53 mmHg.
	With sodium; In ethanol; water; toluene;	(i) diethyl (RS)-formylsuccinate Ethanol (20 cm3) was added portionwise to a suspension of finely divided sodium (10.0 g) in dry toluene (100 cm3). On completion of the addition the mixture was heated for 3.5 hours at 80C. To the resulting yellow suspension, cooled to 20C, was added dropwise, over a period of 1 hour, a mixture of <strong>[123-25-1]diethyl succinate</strong> (70.0 g) and ethyl formate (35.0 g), whilst the temperature of the mixture was maintained in the range 20 to 30C. The mixture was kept at the ambient temperature for 16 hours after which water (100 cm3) was added carefully. The aqueous layer was separated, neutralised with 50% aqueous sulphuric acid, and extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate, and concentrated by evaporation of the solvent under reduced pressure. The residual liquid (66 g) was subjected to fractional distillation under reduced pressure to obtain the desired diethyl (RS)-formylsuccinate (46.0 g), boiling range 82 to 86C/0.53 mmHg. NMR spectroscopy indicated that the product exists as an approximately 1:1 mixture of keto and enol forms. 1H NMR (CDCl3): 1.10-1.40 (m,3H); 2.90 (d, J=7Hz, 1H); 3.05 (s,1H); 3.75 (t, J=7 Hz, 0.5H); 4.00 - 4.40 (m,4H); 7.10 (d,J=II Hz, 0.5H); 9.92 (s, 0.5 H); 11.5 (d, J= 11 Hz, 0.5H). Infra red (liquid film): 3300, 2980, 1735, 1665, 1175, 1030 cmmin1
	With sodium; In diethyl ether; at 0 - 20℃; for 17h;Inert atmosphere;	A mixture of <strong>[123-25-1]diethyl succinate</strong> (26.1 g, 25.0 mL, 0.150 mol) and ethyl formate (11.1 g, 12.1 mL, 0.150 mol) was added drop wise over 1.5 hours to a stirred suspension of sodium (3.40 g, 0. 50 mol) in diethyl ether (120 mL) at 0 C under nitrogen. On completion of addition, stirring was continued at room temperature for 7 hours. Water (120 mL) was cautiously added to the resulting suspension and stirring continued until ail the solids were dissolved. The layers were separated and the aqueous layer was washed with diethyl ether (100 mL). The aqueous layer was then acidified to pH 5 using 11 N HCI and extracted with diethyl ether (3x100 mL), the ethereal extracts of the acidified layer were combined, dried (Na2S04) then evaporated to dryness under reduced pressure to give the title compound (1705) (16.5 g) as a yellow mobile liquid. The crude product was not purified further and was used directly in the following step.
	With sodium; In diethyl ether; at 0 - 20℃; for 17h;Inert atmosphere;	A mixture of <strong>[123-25-1]diethyl succinate</strong> (26.1 g, 25.0 mL, 0.150 mol) and ethyl formate (11.1 g, 12.1 mL, 0.150 mol) was added drop wise over 1.5 hours to a stirred suspension of sodium (3.40 g, 0.150 mol) in diethyl ether (120 mL) at 0 C under nitrogen. On completion of addition, stirring was continued at room temperature for 17 hours. Water (120 mL) was cautiously added to the resulting suspension and stirring continued until all the solids were dissolved. The layers were separated and the aqueous layer was washed with diethyl ether (100 mL). The aqueous layer was then acidified to pH 5 using 11 N HCI and extracted with diethyl ether (3x100 mL), the ethereal extracts of the acidified layer were combined, dried (Na2S04) then evaporated to dryness under reduced pressure to give the title compound (1 /05) (18.5 g) as a yellow mobile liquid. The crude product was not purified further and was used directly in the following step.
	With sodium hydride; In tetrahydrofuran; ethanol; mineral oil; at 10 - 20℃; for 18h;	Step A: Diethyl 2-formylbutanedioate To a stirred suspension of sodium hydride (60% dispersion in mineral oil, 23.0 g, 0.574 mol) in THF (300 mL) was added EtOH (33.5 mL, 0.574 mol) dropwise. The resulting mixture was stirred at ambient temperature for 1 h then cooled to 10 "C and a solution of <strong>[123-25-1]diethyl succinate</strong> (96 mL, 0.574 mol) in THF (100 mL) was added dropwise, followed by a solution of ethyl formate (46.2 mL, 0.574 mol) in THF (100 mL) dropwise. The reaction mixture was stirred at ambient temperature for 18 h, then diluted with water (500 mL) and extracted with diethyl ether (2 x 250 mL), and these organic extracts were discarded. The aqueous layer was acidified to pH = 3-4 by addition of 50% aqueous sulfuric acid and extracted with diethyl ether (2 x 250 mL). The combined organic layers were washed with brine, dried over a2S04, filtered, and concentrated in vacuo. The residue was purified by vacuum distillation to afford the title compound (b.p. 90-92 C at 2 mm Hg). MS: m/z = 203.0 (M + 1).

Reference： [1]Patent: US2013/317021,2013,A1 .Location in patent: Paragraph 0535-0537
[2]Patent: US2013/317022,2013,A1 .Location in patent: Paragraph 0536-0538
[3]Patent: CN103709126,2018,B .Location in patent: Paragraph 0031; 0045; 0046; 0047
[4]Angewandte Chemie - International Edition,2003,vol. 42,p. 1851 - 1853
[5]Patent: WO2020/140054,2020,A1 .Location in patent: Page/Page column 268-269
[6]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2173 - 2176
[7]Patent: WO2005/73234,2005,A2 .Location in patent: Page/Page column 43
[8]Patent: WO2009/152027,2009,A1 .Location in patent: Page/Page column 22; 24-25
[9]Organic Letters,2016,vol. 18,p. 4124 - 4127
[10]Patent: US2011/294788,2011,A1 .Location in patent: Page/Page column 22
[11]Chemistry of Penicillin,
[12]Journal of the American Chemical Society,1911,vol. 33,p. 761
[13]Gazzetta Chimica Italiana,1892,vol. 22 II,p. 440
[14]American Chemical Journal,1907,vol. 38,p. 609
[15]Annales de Chimie (Cachan, France),1922,vol. <9> 17,p. 47
[16]Gazzetta Chimica Italiana,1892,vol. 22 II,p. 440
[17]Patent: US4962109,1990,A
[18]Patent: US4762835,1988,A
[19]Patent: EP295839,1991,A3
[20]Patent: WO2012/110773,2012,A1 .Location in patent: Page/Page column 130; 131
[21]Patent: WO2014/27199,2014,A1 .Location in patent: Page/Page column 132-133
[22]Patent: WO2016/22644,2016,A1 .Location in patent: Page/Page column 72
[23]European Journal of Medicinal Chemistry,2017,vol. 136,p. 548 - 560

3
[ 13321-61-4 ]
[ 5472-38-8 ]
triethyl 5-(carboxymethyl)-2-hydroxymuconate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With benzoic acid In N,N-dimethyl-formamide at 80 - 85℃; for 8h;

Reference： [1]Hajipour, Gholamhossein; Johnson Jr., William H.; Dauben, Paul D.; Stolowich, Neal J.; Whitman, Christian P. [Journal of the American Chemical Society, 1993, vol. 115, # 9, p. 3533 - 3542]

4
[ 5472-38-8 ]
DL-2-methylamino-propionic acid ethyl ester [ No CAS ]
[ 62557-32-8 ]

Reference： [1]Farmaco, Edizione Scientifica,1986,vol. 41,p. 483 - 498

5
[ 5472-38-8 ]
[ 4282-29-5 ]

Reference： [1]Journal of Organic Chemistry,1954,vol. 19,p. 1671,1677

6
[ 5472-38-8 ]
[ 935-72-8 ]

Reference： [1]Journal of Organic Chemistry,1954,vol. 19,p. 1671,1677

7
[ 5472-38-8 ]
[ 53229-47-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: ethanol; sulfuric acid 2: sodium ethylate; diethyl ether 3: toluene; phosphorus (V)-sulfide / Erwaermen des Reaktionsprodukts mit wss.-aethanol. Natronlauge 4: sulfuric acid

Reference： [1]Kornfeld; Jones [Journal of Organic Chemistry, 1954, vol. 19, p. 1671,1677]

8
[ 5472-38-8 ]
[ 867130-58-3 ]

Reference： [1]Journal of the American Chemical Society,1955,vol. 77,p. 3376

9
[ 5472-38-8 ]
[ 876716-99-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: alcohol; hydrazine hydrate 2: aq. barium hydroxide solution

Reference： [1]v.Rothenburg [Chemische Berichte, 1893, vol. 26, p. 2063][Journal fuer Praktische Chemie (Leipzig), 1895, vol. <2>51, p. 142]

10
[ 1903-91-9 ]
[ 5472-38-8 ]
ethyl 2-methoxymethyl-4-hydroxypyrimidine-5-acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	In ethanol;	Step 1, ethyl 2-methoxymethyl-4-hydroxypyrimidine-5-acetate Sodium metal (0.754 mol) was dissolved in absolute ethanol (100 ml) and the resulting solution was added dropwise to a solution of <strong>[1903-91-9]methoxyacetamidine hydrochloride</strong> (0.703 mol) in ethanol (100 ml). After 15 minutes the reaction mixture was filtered and the filtrate was added to a solution of diethyl formylsuccinate (0.703 mol), which was prepared according to H. Nakao et al. Ann. Sankyo Res. Lab., 18, 33-37 (1966). The reaction was refluxed for 15 hours, cooled to room temperature and was then concentrated to obtain a crude solid. This solid was crystallized from isopropanol to obtain the title compound (43% yield), m.p. 142-143 C. 1 H NMR (CDCl3): 7.85 (s, 1H), 4.4 (s, 2H), 4.2 (q, J=7.5 Hz, 2H), 3.5 (s, 3H), 3.4 (s, 2H), 1.2 (t, J=7.5 Hz, 3H).

Reference： [1]Patent: US5789415,1998,A

11
[ 18202-73-8 ]
[ 5472-38-8 ]
5-ethoxycarbonylmethyl-4-hydroxy-2-(2-methylprop-2-yl)-pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium; In ethanol;	(ii) ethyl 2-[2-(1,1-dimethylethyl)-4-hydroxypyrimidin-5-yl]acetate. A solution of sodium ethoxide obtained by dissolving sodium (6.9 g) in ethanol (120 cm3) was added portionwise to a stirred suspension of <strong>[18202-73-8]2,2-dimethylpropionamidine hydrochloride</strong> (41.0 g) in ethanol (150 cm3). The precipitated sodium chloride was removed by filtration. Diethyl (RS)-formylsuccinate (60 g) was added dropwise to the stirred filtrate at the ambient temperature. After keeping the mixture for 16 hours it was heated to the reflux temperature for 1 hour, after which the solvent was removed by evaporation under reduced pressure to give a solid residue which was washed with petroleum ether (boiling range 60-80 C.) to yield ethyl 2-[2-(1,1-dimethylethyl)-4-hydroxypyrimidin-5-yl]acetate (40 g), melting point 98-102 C. A further quantity (15 g) was recovered from the petroleum ether washings by evaporation of the solvent and column chromatographic purification of the residue using a silica column and eluding with a mixture (1:1 by volume) of ethyl acetate and petroleum ether (boiling range 60-80 C.).
	With sodium; In ethanol;	(ii) ethyl 2-[2-(1,1-dimethylethyl)-4-hydroxypyrimidin-5-yl]acetate. A solution of sodium ethoxide obtained by dissolving sodium (6.9 g) in ethanol (120 cm3) was added portionwise to a stirred suspension of <strong>[18202-73-8]2,2-dimethylpropionamidine hydrochloride</strong> (41.0 g) in ethanol (150 cm3). The precipitated sodium chloride was removed by filtration. Diethyl (RS)-formylsuccinate (60 g) was added dropwise to the stirred filtrate at the ambient temperature. After keeping the mixture for 16 hours it was heated to the reflux temperature for 1 hour, after which the solvent was removed by evaporation under reduced pressure to give a solid residue which was washed with petroleum ether (boiling range 60-80C) to yield ethyl 2-[2-(1,1-dimethylethyl)-4-hydroxypyrimidin-5-yl]acetate (40 g), melting point 98-102C. A further quantity (15 g) was recovered from the petroleum ether washings by evaporation of the solvent and column chromatographic purification of the residue using a silica column and eluding with a mixture (1:1 by volume) of ethyl acetate and petroleum ether (boiling range 60-80C).

Reference： [1]Patent: US4962109,1990,A
[2]Patent: EP295839,1991,A3

12
[ 5472-38-8 ]
[ 6214-47-7 ]

Reference： [1]Patent: WO2012/110773,2012,A1
[2]Patent: WO2014/27199,2014,A1
[3]Monatshefte fur Chemie,2016,vol. 147,p. 767 - 773

13
[ 5472-38-8 ]
[ 61727-34-2 ]

Reference： [1]Monatshefte fur Chemie,2016,vol. 147,p. 767 - 773
[2]Patent: WO2016/22644,2016,A1
[3]Patent: WO2009/152027,2009,A1

14
[ 3473-63-0 ]
[ 5472-38-8 ]
[ 6214-46-6 ]

Yield	Reaction Conditions	Operation in experiment
55%		General procedure: A solution of sodium ethoxide in ethanol was cooled to0 C under argon atmosphere. Diethyl 2-formylsuccinatewas added under stirring. After 5 min, the correspondingamidine was added at 0 C and stirring was continued at rtfor 3 days. Aqueous hydrogen chloride solution (5 %) wasadded and it was stirred for 30 min. After addition of waterthe ethanol was removed in vacuo at 30 C. The precipitatewas filtered off to give compound 1 (X = H, Me, Ph, SMe;Y = H, R1 = Et)

Reference： [1]Monatshefte fur Chemie,2016,vol. 147,p. 767 - 773

15
[ 618-39-3 ]
[ 5472-38-8 ]
[ 5810-64-0 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: diethyl 2-formylbutanedioate With sodium ethanolate In ethanol at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: benzamidin In ethanol at 0 - 20℃; for 48h; Inert atmosphere; Stage #3: With hydrogenchloride In ethanol; water at 20℃; for 0.5h; Inert atmosphere;	General procedure I for the synthesis of compounds 1 General procedure: A solution of sodium ethoxide in ethanol was cooled to0 C under argon atmosphere. Diethyl 2-formylsuccinatewas added under stirring. After 5 min, the correspondingamidine was added at 0 C and stirring was continued at rtfor 3 days. Aqueous hydrogen chloride solution (5 %) wasadded and it was stirred for 30 min. After addition of waterthe ethanol was removed in vacuo at 30 C. The precipitatewas filtered off to give compound 1 (X = H, Me, Ph, SMe;Y = H, R1 = Et)

Reference： [1]Kókai, Eszter; Nagy, József; Tóth, Tünde; Kupai, József; Huszthy, Péter; Simig, Gyula; Volk, Balázs [Monatshefte fur Chemie, 2016, vol. 147, # 4, p. 767 - 773]

16
[ 50397-74-5 ]
[ 5472-38-8 ]
(E)-diethyl 2-[((2-bromo-4-cyanophenyl)amino)methylene]succinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	In toluene; for 8h;Reflux;	4-Amino-3-bromobenzonitrile (2.0g, 10.2mmol, 1.0 eq.) was added to a mixture of 8 [34] (5.16g, 25.5mmol, 2.0 eq.) in anhydrous toluene (24mL) under stirring. The resulting mixture was refluxed for 8h. After cooling to rt, the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography (Al2O3, ethyl acetate/cyclohexane, 4/6, v/v) to give the desired product 9 (3.0g, 7.87mmol, 77%) as a white solid. Rf (SiO2, cyclohexane/ethyl acetate, 6/4, v/v): 0.62; Mp: 138-140C; IR (cm-1): 2223 (nuC?N), 1677 (nuC=O), 1625 (nuC=C), 1596 (deltaN-H), 1191 (nuas C-O-C), 1023 (nus C-O-C); 1H NMR (CDCl3, 400MHz) delta 10.68 (d, 1H, 3JNH-Ha=11.6Hz, NH), 7.82 (d, 1H, 4JH3-H5=1.8Hz, H3), 7.54 (dd, 1H, 3JH5-H6=8.6Hz, 4JH5-H3=1.8Hz, H5), 7.22 (d, 1H, 3JHa-NH=11.6Hz, Ha), 7.10 (d, 1H, 3JH6-H5=8.6Hz, H6), 4.27 (q, 2H, 3JHe-Hf or He?-Hf?=7.1Hz, He or He?), 4.17 (q, 2H, 3JHe-Hd or He?-Hd?=7.1Hz, He or He?), 3.24 (s, 2H, Hc), 1.30 (t, 3H, 3JHf-He or Hf?-He?=7.1Hz, He or He?), 1.25 (t, 3H, 3JHf-He or Hf?-He?=7.1Hz, Hf or Hf?); 13C NMR (CDCl3, 100MHz) delta 171.8 (Cd), 168.5 (Cd?), 142.5 (C1), 139.1 (Ca), 136.7 (C3), 132.5 (C5), 117.8 (CN), 112.7 (C6), 111.2 (C2 or C4), 104.9 (C2 or C4), 99.6 (Cb), 60.9 (Ce or Ce?), 60.6 (Ce or Ce?), 36.0 (Cc), 14.2 (2C, Cf, Cf?); HRMS calculated for C16H1779BrN2O4 [M+H]+ m/z 381.0450, found C16H1779BrN2O4 [M+H]+ m/z 381.0476 (100%); C16H1781BrN2O4 [M+H]+ m/z 383.0457 (98%).

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 136,p. 548 - 560

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Code	Phrase
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P378
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P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
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P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
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P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
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P370 + P378	In case of fire:
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Physical hazards
Code	Phrase
H200	Unstable explosive
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H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
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Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
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H315	Causes skin irritation
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H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 5472-38-8 ] {[proInfo.proName]}

Quality Control of [ 5472-38-8 ]

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Application In Synthesis of [ 5472-38-8 ]

[ 5472-38-8 ] Synthesis Path-Upstream 1~6

[ 5472-38-8 ] Synthesis Path-Downstream 1~16

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