57508-48-2|Ethyl 2-Amidinoacetate Hydrochloride| Ambeed

CAS No. :	57508-48-2
Formula :	C₅H₁₁ClN₂O₂
M.W :	166.61
SMILES Code :	O=C(OCC)CC(N)=N.[H]Cl
MDL No. :	MFCD06797615
InChI Key :	VOHFLYOSVGWQOS-UHFFFAOYSA-N
Pubchem ID :	15555354

Safety of [ 57508-48-2 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Application In Synthesis of [ 57508-48-2 ]

* 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.

Downstream synthetic route of [ 57508-48-2 ]

[ 57508-48-2 ] Synthesis Path-Downstream 1~54

1
[ 57508-48-2 ]
[ 1218-69-5 ]
[ 38370-06-8 ]

References: [1]Helvetica Chimica Acta,1972,vol. 55,p. 1566 - 1595.

2
[ 57508-48-2 ]
[ 1972-28-7 ]
[ 26154-49-4 ]

References: [1]Journal of Organic Chemistry,1970,vol. 35,p. 3792 - 3795.

3
[ 542-08-5 ]
[ 126597-33-9 ]
[ 57508-48-2 ]
2-Amino-6-methyl-4-(9-oxo-9H-xanthen-4-yl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-isopropyl ester [ No CAS ]

References: [1]Il Farmaco,1993,vol. 48,p. 1491 - 1502.

4
[ 29816-99-7 ]
[ 126597-33-9 ]
[ 57508-48-2 ]
2-Amino-6-methyl-4-(9-oxo-9H-xanthen-4-yl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-prop-2-ynyl ester [ No CAS ]

References: [1]Il Farmaco,1993,vol. 48,p. 1491 - 1502.

5
[ 1118-84-9 ]
[ 126597-33-9 ]
[ 57508-48-2 ]
allyl ethyl 1,4-dihydro-2-amino-(xanthen-9-one-4-yl)-6-methyl-3,5-pyridindicarboxylate [ No CAS ]

References: [1]Il Farmaco,1993,vol. 48,p. 1491 - 1502.

6
[ 23022-83-5 ]
[ 57508-48-2 ]
[ 111222-44-7 ]

References: [1]Synthesis,1987,p. 272 - 274.

7
[ 1056246-70-8 ]
[ 57508-48-2 ]
[ 111222-46-9 ]

References: [1]Synthesis,1987,p. 272 - 274.

8
[ 57508-48-2 ]
[ 115550-22-6 ]
[ 116796-69-1 ]

References: [1]Chemical and Pharmaceutical Bulletin,1987,vol. 35,p. 4819 - 4828.

9
[ 57508-48-2 ]
[ 115550-25-9 ]
2-Amino-5-(bis-allyloxy-phosphoryl)-6-methyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid ethyl ester; hydrochloride [ No CAS ]

References: [1]Chemical and Pharmaceutical Bulletin,1987,vol. 35,p. 4819 - 4828.

10
[ 57508-48-2 ]
[ 115550-23-7 ]
[ 116796-70-4 ]

References: [1]Chemical and Pharmaceutical Bulletin,1987,vol. 35,p. 4819 - 4828.

11
[ 57508-48-2 ]
[ 116796-68-0 ]
2-Amino-5-(bis-allyloxy-phosphoryl)-6-methyl-4-(2-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid ethyl ester; hydrochloride [ No CAS ]

References: [1]Chemical and Pharmaceutical Bulletin,1987,vol. 35,p. 4819 - 4828.

12
[ 57508-48-2 ]
[ 107431-60-7 ]
3-nitrooxypropyl 2-amino-3-ethoxycarbonyl-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-5-pyridinecarboxylate [ No CAS ]

References: [1]Chemical and Pharmaceutical Bulletin,1993,vol. 41,p. 108 - 116.

13
[ 126597-33-9 ]
[ 57508-48-2 ]
[ 141-97-9 ]
2-Amino-6-methyl-4-(9-oxo-9H-xanthen-4-yl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester [ No CAS ]

References: [1]Il Farmaco,1993,vol. 48,p. 1491 - 1502.

14
[ 126597-33-9 ]
[ 57508-48-2 ]
[ 105-45-3 ]
2-Amino-6-methyl-4-(9-oxo-9H-xanthen-4-yl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester [ No CAS ]

References: [1]Il Farmaco,1993,vol. 48,p. 1491 - 1502.

15
[ 57508-48-2 ]
[ 2114-00-3 ]
[ 111222-43-6 ]

References: [1]Synthesis,1987,p. 272 - 274.

16
[ 57508-48-2 ]
[ 70-11-1 ]
[ 111222-40-3 ]

Yield	Reaction Conditions	Operation in experiment
64%		The following is representative: <strong>[57508-48-2]ethyl 3-amino-3-iminopropanoate hydrochloride</strong> (3) (8.3 g, 50.0 mmol) and NaOEt (5.1 g, 75.0 mmol) were dissolved in abs. EtOH at 0 C and stirred for 20 min under argon. The mixture was heated to 60 C, and 2-bromo-1-phenylethanone (4b) (5.0 g, 25.0 mmol) was added portion wise over 5 min. After 1.5 h the mixture was cooled to 20 C and the solvent was evaporated under reduced pressure. The residue was diluted with distilled water (20 mL) and extracted with EtOAc (3 × 80 mL). The organic layer was washed with water (3 × 20 mL) and brine (3 × 20 mL). The combined water fractions were back extracted with EtOAc (2 × 20 mL). The organic phases were dried over MgSO4, and the solvent was evaporated under reduced pressure. Purification was by silica-gel column chromatography (EtOAc/n-pentane, 7/3).
64%		Pyrrolopyrimidines route 1 The following is representative: Ethyl 2-amino-5-phenyl-lH-pyrrole-3-carboxylate (25) Ethyl 3-amino-3-iminopropanoate hydrochloride (23) (8.3 g, 50.0 mmol) and NaOEt (5.1 g, 75.0 mmol) were dissolved in abs. EtOH at 0 C and stirred for 20 min. under argon. The mixture was heated to 60 C, and 2-bromo-l-phenylethanone (24) (5.0 g, 25.0 mmol) was added portion wise over 5 min. After 1.5 h the mixture was cooled to 20 C and the solvent was evaporated under reduced pressure. The residue was diluted with distilled water (20 mL) and extracted with EtOAc (3 X80 mL). The organic layer was washed with water (3 X20 mL) and brine (3 X20 mL). The combined water fractions were back extracted with EtOAc (2X20 mL). The organic phases were dried over MgSC^, and the solvent was evaporated under reduced pressure. Purification was by silica-gel column chromatography (EtOAc/n-pentane, 7/3). This gave 3.7 g (16.1 mmol, 64%) of a beige solid, mp. 101-104 C; 1H NMR (400 MHz, DMSO-<) delta: 10.72 (s, 1H, NH), 7.50-7.44 (m, 2H), 7.32-25 (m, 2H), 7.1 1-7.05 (m, 1H), 6.46 (d, J=2.4, 1H), 5.65 (s, 2H), 4.15 (q, J=6.8, 2H), 1.25 (t, J=6.8, 3H). 13C NMR (100 MHz, DMSO-<), delta: 165.4, 148.6, 132.6, 129.1 (2C), 125.4, 123.6, 122.8 (2C), 104.0, 93.9, 58.6, 15.2. HRMS (ESI): 231.1 124 (calcd C13H14N2O2, 231.1 128, M+H+). IR (neat, cm"1): 3417, 3328, 1662, 1589, 1281 , 1 120, 757, 691.

References: [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 6002 - 6014.
[2]Patent: WO2015/959,2015,A1 .Location in patent: Page/Page column 58-59.
[3]Synthesis,1987,p. 272 - 274.

17
[ 57508-48-2 ]
[ 1655-07-8 ]
[ 111655-66-4 ]

References: [1]Zeitschrift fur Chemie,1987,vol. 27,p. 69 - 70.

18
[ 57508-48-2 ]
[ 1775-27-5 ]
[ 111222-45-8 ]

References: [1]Synthesis,1987,p. 272 - 274.

19
[ 57508-48-2 ]
[ 1484-50-0 ]
[ 111222-42-5 ]

References: [1]Farmaco, Edizione Scientifica,1988,vol. 43,p. 103 - 112.
[2]Synthesis,1987,p. 272 - 274.

20
[ 57508-48-2 ]
[ 94-05-3 ]
[ 130484-63-8 ]

References: [1]Journal of Heterocyclic Chemistry,1990,vol. 27,p. 1143 - 1151.

21
[ 57508-48-2 ]
[ 814-75-5 ]
[ 111222-41-4 ]

References: [1]Synthesis,1987,p. 272 - 274.

22
[ 27317-59-5 ]
[ 57508-48-2 ]

Yield	Reaction Conditions	Operation in experiment
78%	With ammonium chloride; In ethanol; at 120℃; for 1h;Microwave irradiation;	A solution of ethyl 3-amino-3-ethoxypropenoate 10 (760 mg, 4.78 mmol) and NH4Cl (270 mg, 5.0 mmol) in EtOH (4.0 mL) was irradiated in a pressure-rated glass tube (10 mL) at 120 C for 1 h (hold-time) using a CEM Discover microwave synthesizer by moderation of the initial magnetron power (200 W). After cooling in a flow of compressed air, the solution was filtered, evaporated in vacuo and triturated with diethylether to give the title compound1 (923 mg, 78%) as a colourless solid, which was used without further purification; numax (neat) /cm-1 3300, 3095,1738, 1687; deltaH (500 MHz; d6-DMSO) /ppm 9.16 (2H, bs, NHH), 8088 (2H, bs, 2H, NHH), 4.15 (2H, q, J = 7.1 Hz, OCH2), 3.63 (2H, s, 2-H),1.22 (3H, t, J = 7.1 Hz, Me); deltaC (125 MHz, d6-DMSO) /ppm 166.7 (C), 163.6 (C), 61.9 (CH2), 38.2 (CH2), 14.4 (Me); m/z (EI) 130 (M?+).
	With ammonium chloride; In ethanol; for 8h;Heating / reflux;	To anhydrous ethanol (460 g, 10.0 mol) at -3O0C was bubbled in anhydrous hydrogen chloride until the total weight of 821 g of HCl/EtOH solution (44% (w/w) was obtained.Ethyl cyanoacetate (452 g) was added into the HCl/EtOH solution (292 g), the mixture was cooled to ice-salt bath temperature and stirred for 1 hours. The reaction was warmed to room temperature and stood overnight. A white precipitate of 102 was obtained and this mixture was used directly in the next step.The obtained mixture was added to a mixture of ether and a solution OfK2CO3(828 g) in water (2500 mL). The ether layer was separated, dried over Na2SO^ and filtered. The filtrate was concentrated under reduced pressure to give compound 103 (445 g) as a colorless oil.A mixture of compound 103 (445 g) and ammonium chloride (149.5 g) in ethanol(1500 mL) was heated to reflux for 8 h. The solid was isolated and the filtrate was concentrated. The residue was washed with ether and acetone to give product 104 (220 g, 33% total yield in three steps). LCMS: 131 [M+l]+, 1H NMR (DMSO-(Z6): delta 1.22 (t, J = 6.9 Hz, 3H), 3.68 (s, 2H), 4.16 (q, J = 6.9 Hz, 2H), 9.04 (s, 2H), 9.32 (s, 2H).
	With ammonium chloride; In ethanol; for 8h;Heating / reflux;	To anhydrous ethanol (460 g, 10.0 mol) at -3O0C was bubbled in anhydrous hydrogen chloride until the total weight of 821 g of etaCl/EtOeta solution (44% (w/w) was obtained.Ethyl cyanoacetate (452 g) was added into the etaCl/EtOeta solution (292 g), the mixture was cooled to ice-salt bath temperature and stirred for 1 hours. The reaction <n="256"/>was warmed to room temperature and stood overnight. A white precipitate of 102 was obtained and this mixture was used directly in the next step.The obtained mixture was added to a mixture of ether and a solution OfK2COs (828 g) in water (2500 mL). The ether layer was separated, dried over Na2SO4, and filtered. The filtrate was concentrated under reduced pressure to give compound 103 (445 g) as a colorless oil.A mixture of compound 103 (445 g) and ammonium chloride (149.5 g) in ethanol (1500 mL) was heated to reflux for 8 h. The solid was isolated and the filtrate was concentrated. The residue was washed with ether and acetone to give product 104 (220 g, 33% total yield in three steps). LCMS: 131 [M+l]+, 1H NMR (DMSO-J6): delta 1.22 (t, J= 6.9 Hz, 3H), 3.68 (s, 2H), 4.16 (q, J= 6.9 Hz, 2H), 9.04 (s, 2H), 9.32 (s, 2H).

References: [1]Synlett,2016,vol. 27,p. 1728 - 1732.
[2]Chemical and Pharmaceutical Bulletin,1995,vol. 43,p. 788 - 796.
[3]Patent: WO2008/33745,2008,A2 .Location in patent: Page/Page column 70.
[4]Patent: WO2008/33747,2008,A2 .Location in patent: Page/Page column 254-255.
[5]European Journal of Medicinal Chemistry,2011,vol. 46,p. 6002 - 6014.

23
[ 27996-87-8 ]
[ 57508-48-2 ]
2-amino-3-ethoxycarbonyl-6-nitroquinoline [ No CAS ]
[ 851266-02-9 ]
diethyl 2,6-diamino-4-(2-fluoro-5-nitrophenyl)-4,5-dihydropyridine-3,5-dicarboxylate [ No CAS ]

References: [1]Chemistry of Heterocyclic Compounds,2004,vol. 40,p. 888 - 894.

24
[ 57508-48-2 ]
[ 2632-13-5 ]
[ 173458-92-9 ]

Yield	Reaction Conditions	Operation in experiment
67%	With sodium ethanolate; In ethanol; at 0 - 20℃;	To the solution of EtONa (4.08 g, 60 mmol) in EtOH (60 mL) was added compound 104 (10 g, 60 mmol) at 0 0C under nitrogen. The mixture was stirred for 20 minutes and 2-bromo-4'-methyloxy-acetophenone was added. After stirring at room temperature overnight, the mixture was concentrated and the residue was taken up in ethyl acetate, washed with water, brine, dried and concentrated to give a residue which was purified by column chromatography to afford the product 402 as a solid (5.2 g, 67 %yield). 1H NMR (DMSOd6) delta 10.62 (s, IH), 7.41 (d, J = 6.6 Hz, 2H), 6.88 (d, J = 6.6 Hz, 2H), 6.30 (d, J = 3.0 Hz, IH), 5.59 (s, 2H), 4.13 (q, J = 6.9 Hz, 2H), 3.74 (s, 3H), 1.24 (t, J = 7.2 Hz, 3 H). LC-MS: 260 (M+l).
67%		To the solution of EtONa (4.08 g, 60 mmol) in EtOH (60 mL) was added compound 104 (10 g, 60 mmol) at 0 0C under nitrogen. The mixture was stirred for20 minutes and 2-bromo-4'-methyloxy-acetophenone was added. After stirring at room temperature overnight, the mixture was concentrated and the residue was taken up in ethyl acetate, washed with water, brine, dried and concentrated to give a residue which was purified by column chromatography to afford the product 402 as a solid (5.2 g, 67 %yield). 1H NMR (DMSO-d6) delta 10.62 (s, 1eta), 7.41 (d, J = 6.6 Hz,2H), 6.88 (d, J = 6.6 Hz, 2H), 6.30 (d, J = 3.0 Hz, IH), 5.59 (s, 2H), 4.13 (q, J = 6.9 Hz, 2H), 3.74 (s, 3H), 1.24 (t, J = 7.2 Hz, 3 H). LC-MS: 260 (M+l).
		General procedure: The following is representative: <strong>[57508-48-2]ethyl 3-amino-3-iminopropanoate hydrochloride</strong> (3) (8.3 g, 50.0 mmol) and NaOEt (5.1 g, 75.0 mmol) were dissolved in abs. EtOH at 0 C and stirred for 20 min under argon. The mixture was heated to 60 C, and 2-bromo-1-phenylethanone (4b) (5.0 g, 25.0 mmol) was added portion wise over 5 min. After 1.5 h the mixture was cooled to 20 C and the solvent was evaporated under reduced pressure. The residue was diluted with distilled water (20 mL) and extracted with EtOAc (3 × 80 mL). The organic layer was washed with water (3 × 20 mL) and brine (3 × 20 mL). The combined water fractions were back extracted with EtOAc (2 × 20 mL). The organic phases were dried over MgSO4, and the solvent was evaporated under reduced pressure. Purification was by silica-gel column chromatography (EtOAc/n-pentane, 7/3).

References: [1]Magnetic Resonance in Chemistry,2010,vol. 48,p. 244 - 248.
[2]Patent: WO2008/33745,2008,A2 .Location in patent: Page/Page column 65.
[3]Patent: WO2008/33747,2008,A2 .Location in patent: Page/Page column 250.
[4]European Journal of Medicinal Chemistry,2011,vol. 46,p. 6002 - 6014.

25
[ 2318-25-4 ]
[ 57508-48-2 ]

References: [1]Chemical and Pharmaceutical Bulletin,1995,vol. 43,p. 788 - 796.
[2]Letters in drug design and discovery,2014,vol. 11,p. 1143 - 1148.
[3]Synlett,2016,vol. 27,p. 1728 - 1732.

26
[ 105-56-6 ]
ortho-dichlorobenzene(tricarbonyl)chromium [ No CAS ]
[ 57508-48-2 ]

References: [1]Chemical and Pharmaceutical Bulletin,1995,vol. 43,p. 788 - 796.

27
14-bromo-3-(3-nitrobenzylidene)tetradecane-2,4-dione [ No CAS ]
[ 57508-48-2 ]
ethyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-5-(11-bromo-1-oxo-undecyl)pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium methylate; In ethanol; ethyl acetate;	D1. Ethyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-5-(11-bromo-1-oxo-undecyl)pyridine-3-carboxylate 12.7 g of ethyl amidinoacetate hydrochloride and 33.4 g of 14-bromo-3-(3-nitrobenzylidene)tetradecane-2,4-dione are dissolved in 300 ml of ethanol and the solution is treated with 14.5 ml of a 5.25M of sodium methoxide solution. The mixture is heated to boiling under reflux for 7 h and then concentrated in vacuo. The residue is dissolved in ethyl acetate and the solution is washed with water, dried over sodium sulfate, filtered and concentrated again. The oily residue is dried in vacuo and reacted in the next stage without further purification.

References: [1]Patent: US5925642,1999,A .

28
[ 141-52-6 ]
[ 57508-48-2 ]
[ 2632-13-5 ]
[ 173458-92-9 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol;	Step 12.1: 2-Amino-3-ethoxycarbonyl-5-(4-methoxy-phenyl)-1H-pyrrole Analogously to Step 8.1, 1.67 g (10 mmol) of 2-amidino-acetic acid ethyl ester hydro-chloride in 20 ml of abs. ethanol are reacted with 716 mg (10 mmol) of sodium ethanolate and 1.145 g (5.0 mmol) of 4-methoxy-phenacyl bromide (Fluka; Buchs/Switzerland) to form the title compound; m.p. 141-142 C.; TLC-Rf =0.4 (hexane/ethyl acetate [1:1]); FAB-MS: (M+H)+ =261.

References: [1]Patent: US6140332,2000,A .

29
[ 31949-21-0 ]
[ 141-52-6 ]
[ 57508-48-2 ]
[ 173458-96-3 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol;	Step 10.1: 2-Amino-3-ethoxycarbonyl-5-(2-methoxy-phenyl)-1H-pyrrole Analogously to Step 8.1, 14.5 g (87 mmol) of 2-amidino-acetic acid ethyl ester hydrochloride in 150 ml of abs. ethanol are reacted with 5.9 g (87 mmol) of sodium ethanolate and 10.3 g (44 mmol) of 2-bromo-1-(2-methoxy-phenyl)-ethan-1-one (2-bromo-2'-methoxy-acetophenone; Aldrich; Milwaukee/USA) to form the title compound; m.p.: 128 C.; TLC-Rf =0.25 (hexane/ethyl acetate [2:1]).

References: [1]Patent: US6140332,2000,A .

30
[ 141-52-6 ]
[ 57508-48-2 ]
[ 5000-65-7 ]
[ 173458-95-2 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol;	Step 11.1: 2-Amino-3-ethoxycarbonyl-5-(3-methoxy-phenyl)-1H-pyrrole Analogously to Step 8.1, 14.5 g (87 mmol) of 2-amidino-acetic acid ethyl ester hydro-chloride in 150 ml of abs. ethanol are reacted with 5.9 g (87 mmol) of sodium ethanolate and 10.3 g (44 mmol) of 2-bromo-1-(3-methoxy-phenyl)-ethan-1-one (2-bromo-3'-methoxy-acetophenone; Janssen) to form the title compound; m.p. 96-97oC; TLC-Rf =0.2 (hexane/ethyl acetate [2:1]).

References: [1]Patent: US6140332,2000,A .

31
2-bromo-(4-ethoxycarbonyl)-acetophenone [ No CAS ]
[ 141-52-6 ]
[ 57508-48-2 ]
[ 187724-91-0 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol;	Step 30.1: 2-Amino-3-ethoxycarbonyl-5-(4-ethoxycarbonyl-phenyl)-1H-pyrrole Analogously to Step 8.1, 4.92 g (29.5 mmol) of 2-amidino-acetic acid ethyl ester hydrochloride in 40 ml of absolute ethanol are reacted with 2.0 g (29.5 mmol) of sodium ethanolate and 4.0 g (14.8 mmol) of 2-bromo-(4-ethoxycarbonyl)-acetophenone to form the title compound; m.p.: 150-151 C.; MS: (M)+ =302.

References: [1]Patent: US6140332,2000,A .

32
[ 5765-44-6 ]
[ 57508-48-2 ]
[ 147440-88-8 ]
ethyl 2-amino-5-cyano-6-methyl-4-(3-phenyl-1,7-naphthyridin-5-yl)-1,4-dihydropyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium; acetic acid; In ethanol; ethyl acetate; toluene;	EXAMPLE 1 Ethyl 2-amino-5-cyano-6-methyl-4-(3-phenyl-1,7-naphthyridin-5-yl)-1,4-dihydropyridine-3-carboxylate STR24 2 g (8.5 mmol) of 3-phenyl-1,7-naphthyridine-5-carboxaldehyde are suspended in 20 ml of ethanol and stirred with 0.7 ml (8.5 mmol) of 5-methylisoxazole. A solution of 196 mg of sodium in 14 ml of ethanol is added and the mixture is stirred for 2 hours at 50 C. 1.42 g of ethyl amidinoacetate hydrochloride and 0.51 ml (8.5 mmol) of acetic acid are added and the mixture is boiled for 16 hours. After cooling, 10 g of silica gel are added and the mixture is concentrated in vacuo. The residue is chromatographed on a silica gel column using toluene/ethyl acetate mixtures. After concentration of the pure fractions, the product is crystallized by trituration with ether. 2 g of crystals are obtained.

References: [1]Patent: US5434153,1995,A .

33
[ 10230-68-9 ]
[ 138251-24-8 ]
[ 57508-48-2 ]
ethyl 2-amino-6-methyl-5-nitro-4-(3-phenyl-5-quinolyl)-1,4-dihydropyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium acetate; In ethanol; water; ethyl acetate; toluene;	EXAMPLE 1 Ethyl 2-amino-6-methyl-5-nitro-4- (3-phenyl-5-quinolyl)-1,4-dihydropyridine-3- carboxylate STR18 1.66 g (10 mmol) of ethyl amidinoacetate hydrochloride, 1.8 g (17.5 mmol) of nitroacetone and 820 mg (10 mmol) of sodium acetate are added to 2.33 g (10 mmol) of 3-phenylquinoline-5-carbaldehyde in 20 ml of ethanol, and the mixture is heated at reflux for 30 min. The dark red solution obtained is cooled and concentrated. The residue is dissolved in ethyl acetate/water, the phases are separated, and the ethyl acetate phase is extracted with sodium hydrogen carbonate solution and water, dried and concentrated. The mixture obtained is purified on a silica gel column using toluene/ethyl acetate in a volume ratio of 2:1. The pure fractions are collected and concentrated. By crystallization from acetonitrile, 116 mg of yellow crystals with a melting point of 252-253 C. are obtained.

References: [1]Patent: US5502062,1996,A .

34
3-nitrooxypropyl 2-(3-nitrobenzylidene)acetoacetate [ No CAS ]
[ 57508-48-2 ]
3-nitrooxypropyl 2-amino-3-ethoxycarbonyl-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-5-pyridinecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With sodium methylate; In ethyl acetate;	EXAMPLE 1 3-Ethyl 5-(3-nitrooxypropyl) 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl) pyridine-3,5-dicarboxylate (Compound No. 30) 400 ml of an ethanolic solution containing 14 g (41 mmoles) of 3-nitrooxypropyl 2-(3-nitrobenzylidene)acetoacetate, 6.9 g (41 mmoles) of ethyl amidinoacetate hydrochloride and 2.24 g (41 mmoles) of sodium methoxide were heated under reflux for 7 hours, The solution was then cooled, insolubles were filtered off and the ethanol was evaporated off under reduced pressure. The resulting residue was dissolved in ethyl acetate and this solution was washed with water and then dried over anhydrous sodium sulfate. The ethyl acetate was evaporated off under reduced pressure, and the resulting residue was subjected to column chromatography through silica gel, eluted with a 2:1 by volume mixture of toluene and ethyl acetate, to give 14.5 g (yield 79%) of the title compound as orange plate-like crystals, melting at 140-141.5 C.

References: [1]Patent: US4992451,1991,A .

35
ethyl ether-ethyl acetate [ No CAS ]
2-(4-benzhydryl-1-piperazinyl)ethyl 2-(3-nitrobenzylidene)acetoacetate [ No CAS ]
[ 57508-48-2 ]
[ 98290-99-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium ethanolate; sodium; In ethanol;	(2) Sodium (0.20 g) was dissolved in dry ethanol (10 ml) and the thus-obtained sodium ethylate solution was added dropwise to a solution of 2-(4-benzhydryl-1-piperazinyl)ethyl 2-(3-nitrobenzylidene)acetoacetate (4.37 g) and ethyl amidinoacetate hydrochloride (1.42 g) in dry ethanol (10 ml) with stirring under reflux over a period of about 15 minutes. The mixture was further refluxed for 5 minutes. The resulting NaCl was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (120 g). From the elude with ethyl ether-ethyl acetate (10:1, v/v), there was obtained 5-[2-(4-benzhydryl-1-piperazinyl)ethyl] 3-ethyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate as a yellow powder. Yield 3.22 g.

References: [1]Patent: US4603135,1986,A .

36
[3-(4,4-diphenylpiperid-1-yl)-propyl] 2-acetyl-3-(3-nitrophenyl)-acrylate hydrochloride [ No CAS ]
[ 57508-48-2 ]
[ 114316-06-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium; In methanol; diethyl ether; ethanol; Petroleum ether;	4. 3-Ethyl 5-[3-(4,4-diphenylpiperid-1-yl)-propyl]2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-pyridine-3,5-dicarboxylate A sodium ethylate solution prepared from 0.46 g of sodium and 20 ml of ethanol is added dropwise at the boiling point to a solution of 5.49 g of [3-(4,4-diphenylpiperid-1-yl)-propyl] 2-acetyl-3-(3-nitrophenyl)-acrylate hydrochloride and 1.67 g of ethyl amidinoacetate hydrochloride in 15 ml of ethanol in the course of 60 minutes and the mixture is then boiled under reflux for about a further 30 minutes. After the reaction mixture has been concentrated, the resulting residue is partitioned between ethyl acetate, sodium bicarbonate solution and then water. After drying over sodium sulfate, the organic phase is concentrated and the residue is chromatographed over a 3*30 cm silica gel column with methylene chloride/ethanol (95+5) as the eluant. The product fraction is concentrated and the solid foamed residue is taken up in a little methanol. After addition of diethyl ether/petroleum ether (1+1) until slight clouding first persists, the mixture is left to stand in a refrigerator for 24 h. The title compound crystallizes out in the form of fine platelets of m.p. 174-175 C. Yield: 4.4 g.

References: [1]Patent: US5064839,1991,A .

37
3-(4,4-diphenylpiperid-1-yl)-propyl 2-acetyl-3-(4-benzo[c][1.2.5]oxadiazolyl)-acrylate [ No CAS ]
[ 57508-48-2 ]
[ 114332-61-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium; In methanol; diethyl ether; ethanol;	8. 3-Ethyl 5-[3-(4,4-diphenylpiperid-1-yl)-propyl] 2-amino-4-(4-benzo[c][1.2.5]oxadiazolyl)-1,4-dihydro-6-methyl-pyridine-3,5-dicarboxylate The title compound is obtained analogously to Example 4 from 6.11 g of 3-(4,4-diphenylpiperid-1-yl)-propyl 2-acetyl-3-(4-benzo[c][1.2.5]oxadiazolyl)-acrylate, 2.01 g of ethyl amidinoacetate hydrochloride and 276 mg of sodium in 35 ml of absolute ethanol, as fine yellowish crystal platelets of m.p.: 127-131 C. [slow deliquescence, from methanol/diethyl ether); yield: 2.7 g.

References: [1]Patent: US5064839,1991,A .

38
[ 114316-24-4 ]
[ 57508-48-2 ]
[ 114316-10-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium; In methanol; diethyl ether; ethanol;	10. 3-Ethyl 5-[3-(4,4-diphenylpiperid-1-yl)-propyl]2-amino-1,4-dihydro-6-methyl-4-(2-trifluoromethylphenyl)-pyridine-3,5-dicarboxylate The title compound is obtained analogously to Example 4 from 4.28 g of 3-(4,4-diphenylpiperid-1-yl)-propyl 2-acetyl-3-(2-trifluoromethylphenyl)-acrylate, 1.33 g of ethyl amidinoacetate hydrochloride and 184 g of sodium in 40 ml of absolute ethanol, as fine yellowish crystal platelets of m.p.: 115-117 C. (from methanol/diethyl ether), yield: 3.32 g.

References: [1]Patent: US5064839,1991,A .

39
decyl 2-(3-nitrobenzylidene)acetoacetate [ No CAS ]
[ 57508-48-2 ]
[ 88284-41-7 ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium; In ethanol;	Example 20 5-Decyl 3-ethyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate STR56 A solution of 1.15 g (50 mmol) of sodium in 100 ml of ethanol was added dropwise at room temperature, with stirring, to a solution of 18.8 g (50 mmol) of decyl 2-(3-nitrobenzylidene)acetoacetate and 8.3 g (50 mmol) of ethyl amidinoacetate hydrochloride in 250 ml of ethanol. The mixture was then heated to boiling for 15 minutes. After standing overnight, the precipitated sodium chloride was filtered off, the filtrate was evaporated in vacuo and the oily residue was brought to crystallization by trituration with ether/petroleum ether. The crude product was filtered off with suction and recrystallized from ethanol, melting point: 190-191 C. Yield: 65% of theory.

References: [1]Patent: US4622332,1986,A .

40
2-carbethoxy-3-oxotetrahydrothiapyran [ No CAS ]
[ 57508-48-2 ]
2-(Carboethoxymethyl)-7,8-dihydro-6H-thiapyrano[3,2-d]pyrimidin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; ethanol;	A. 2-(Carboethoxymethyl)-7,8-dihydro-6H-thiapyrano[3,2-d]pyrimidin-4-one Treatment of 299 mg of ethyl amidinoacetate hydrochloride (D. J. Collins, J. Chem. Soc. 1337 (1963). Difficulty was experienced in getting reproducibly satisfactory preparations of this intermediate.) with 333 mg of ethyl 3-oxotetrahydrothiapyran-2-carboxylate by a modification of Procedure I in which ethanol was substituted for methanol gave a product which could not be crystallized so the reaction mixture was concentrated to dryness and the residue was triturated with ether. In this manner 314 mg of product was obtained and used directly in the next step. The mass spectrum and 200 MHz pmr spectrum of this product were satisfactory.

References: [1]Patent: US4871739,1989,A .

41
[ 1074-86-8 ]
[ 935758-14-8 ]
[ 57508-48-2 ]
2-amino-4-(1H-indol-4-yl)-5-oxo-7-(2,4,6-trimethyl-phenyl)-1,5,7,8-tetrahydro-4H-pyrano[4,3-b]pyridine-3-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium acetate; 1-butyl-3-methylimidazolium Tetrafluoroborate; at 100℃; for 1 - 2h;	Example 109[0407] Preparation of 2-Amino-4-(lH-indol-4-yl)-5-oxo-7-(2,4,6-trimethyI-phenyl)- l,5,7,8-tetrahydro-4H-pyrano[4,3-b]pyridine-3-carboxylic acid ethyl ester. <n="150"/>[0408] Synthesis of 2-Amino-4-(lH-indol-4-yl)-5-oxo-7-(2,4,6-trimethyl-phenyI)- l,5,7,8-tetrahydro-4H-pyrano[4,3-b]pyridine-3-carboxylic acid ethyl ester (13oo): Ethyl amidinoacetate acetic acid salt is added to a 25-mL flask followed by lactone (1 equiv) and indole-4-carboxaldehyde (1 equiv). l-Butyl-3-methylimidazolium tetrafluoroborate (approx 2-3 drops/mmol of substrate) is added and the reaction mixture stirred at 100 0C for 1-2 hours. After completion (determined by LCMS), the reaction slurry is diluted with EtOAc and saturated NaHCO3. The organic layer is collected and the aqueous layer further extracted with 3 x EtOAc. The product is purified in 25-80% EtOAc in hexanes. MS (ES) M+H expect 472.2, found 472.2.

References: [1]Patent: WO2007/51062,2007,A2 .Location in patent: Page/Page column 148-149.

42
[ 20099-89-2 ]
[ 57508-48-2 ]
[ 497841-33-5 ]

Yield	Reaction Conditions	Operation in experiment
48%		General procedure: The following is representative: <strong>[57508-48-2]ethyl 3-amino-3-iminopropanoate hydrochloride</strong> (3) (8.3 g, 50.0 mmol) and NaOEt (5.1 g, 75.0 mmol) were dissolved in abs. EtOH at 0 C and stirred for 20 min under argon. The mixture was heated to 60 C, and 2-bromo-1-phenylethanone (4b) (5.0 g, 25.0 mmol) was added portion wise over 5 min. After 1.5 h the mixture was cooled to 20 C and the solvent was evaporated under reduced pressure. The residue was diluted with distilled water (20 mL) and extracted with EtOAc (3 × 80 mL). The organic layer was washed with water (3 × 20 mL) and brine (3 × 20 mL). The combined water fractions were back extracted with EtOAc (2 × 20 mL). The organic phases were dried over MgSO4, and the solvent was evaporated under reduced pressure. Purification was by silica-gel column chromatography (EtOAc/n-pentane, 7/3).
	With sodium ethanolate; In ethanol;	Step 40.1: 2-Amino-5-(4-cyano-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester A mixture of 42.53 g (0.255 mol) carbamimidoyl-acetic acid ethyl ester hydrochloride in 70 ml absolute ethanol is treated at 0 to 5 C. with 95.3 ml of a 21% sodium ethoxide solution in ethanol (0.255 mol) and stirred 5 min at 0 to 5 C. 4-Bromoacetyl-benzonitrile (28.6 g, 0.128 mol) is then added in portions over 20 min at 0 to 5 C. Stirring is continued at this temperature for 5 min then the ice bath is removed and the yellow suspension is stirred over night at RT. The solid is filtered off, washed with ethanol and ether and re-suspended in 450 ml actonitrile. The mixture is heated for 5 min under reflux, filtered while still hot and then cooled in an ice bath. The title compoundcompound is collected by succion and dried. Flash chromatography (dichloromethane/ethyl acetate mixture) of the mother liquors gives an additional crop of the title compound as a yellow solid; m.p. 228-229 C.; MS-ES+: (M+H)+=254.

References: [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 6002 - 6014.
[2]Patent: US2004/248911,2004,A1 .

43
[ 4254-67-5 ]
[ 57508-48-2 ]
[ 417721-39-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium ethanolate; In ethanol; water; ethyl acetate;	Production Example 153-1 2-Amino-5-(4-benzyloxyphenyl)-1H-pyrrole-3-carboxylic acid ethyl ester After adding 700 ml of ethanol to 50.7 g of <strong>[57508-48-2]ethyl 2-amidinoacetate hydrochloride</strong> (a publicly known compound described in Liebigs Ann. Chem., 1895(1977)), the mixture was stirred at room temperature, 22.3 g of sodium ethoxide (1 equivalent with respect to <strong>[57508-48-2]ethyl 2-amidinoacetate hydrochloride</strong>) was added, and the mixture was stirred for 15 minutes under a nitrogen atmosphere. To this there was added 49.9 g of 1-(4-benzyloxyphenyl)-2-bromoethanone (publicly known compound described in Journal of Heterocyclic Chemistry, vol.2, 310(1965) and Journal of Medicinal Chemistry, vol.17, 55(1974)), and the mixture was stirred for 36 hours at room temperature under a nitrogen atmosphere. Water was added, ethyl acetate was used for liquid separation and extraction, and then the organic layer was dried over sodium sulfate and concentrated to dryness to obtain 56.7 g of the title compound. 1H-NMR Spectrum: (DMSO-d6) 1.32 (3H, t, J=7.3 Hz), 4.10(2H, q, J=7.3 Hz), 5.08(2H, s,), 5.62(2H, s), 6.30 (1H, d, J=2.2 Hz), 6.95 (2H, d, J=7.9 Hz), 7.28-7.47 (7H, m), 10.67(1H,brs)

References: [1]Patent: US2004/53908,2004,A1 .

44
[ 57508-48-2 ]
[ 56893-25-5 ]
[ 1011716-95-2 ]

Yield	Reaction Conditions	Operation in experiment
85.3%		Sodium (1.38 g, 60 mmol) was added to ethanol (150 mL) and stirred until the sodium was dissolved. The reaction was cooled to 0 0C and a solution of <strong>[57508-48-2]ethyl 2-amidinoacetate hydrochloride</strong> (10.0 g, 0.06 mol) was added and stirred for 30 min. Methyl 4-(2-bromoacetyl)benzoate 106 (7.71 g, 0.03 mol) was then added. The resulting mixture was stirred at room temperature for 24 h. The reaction mixture was concentrated and the residue was dissolved with ethyl acetate, filtered and the filtrate was washed with water. The aqueous phase was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over MgSO4 and filtered. The filtrate was concentrated and the residue was purified by column chromatography to give the compound 107 (7.38 g, 85.3%). LCMS: 289 [M+l]+; 1H <n="257"/>NMR (DMSO-J6) : delta 1.25 (t, J= 6.9 Hz, 3H), 3.82 (s, 3H), 4.14 (q, J= 6.9 Hz, 2H), 5.81 (s, 2H), 6.71 (s, IH), 7.61 (d, J= 8.7 Hz, 2H), 7.84 (d, J= 8.7 Hz, 2H), 10.94 (s, IH).
56.7%		Step-I: Ethyl 2-amino-5-(4-methoxycarbonylphenyl)-1H-pyrrole-3-carboxylate (XI-7-I) Na metal (1.96 g, 85.3 mmol) was added portion wise to ethanol (210 mL) and stirred for 30 minutes to get clear solution. To this was added ethyl 3-amino-3-imino-propanoate hydrochloride (CAS: 57508-48-2, 14.25 g, 85.6 mmol) and stirred at room temperature for additional 30 minutes. Finally, methyl 4-(2-bromoacetyl)benzoate (11 g, 42.8 mmol) was added to the reaction mixture and stirred for 16-20 h at room temperature. After completion of the reaction (as indicated by TLC and LCMS), reaction mixture was filtered through celite and the residue was washed with MeOH (50 mL*2). The combined filtrate was concentrated under reduced pressure and the residue was purified using silica gel column chromatography (40% EtOAc in hexane) to provide XI-7-I (7 g, 56.7% yield). LCMS; m/z: 289.1 (M+1)+.

References: [1]Patent: WO2008/33747,2008,A2 .Location in patent: Page/Page column 255.
[2]Patent: US2015/64196,2015,A1 .Location in patent: Paragraph 0230.

45
[ 57508-48-2 ]
[ 99-81-0 ]
[ 187724-88-5 ]

Yield	Reaction Conditions	Operation in experiment
79.5%		Under a nitrogen atmosphere, compound 104(16.7 g, 100 mmol) was introduced into 25 mL of ethanol at 0~5 C followed by sodium ethanolate (6.8 g, 100 mmol). The yellow suspension was stirred for 20 minutes and compound 501 (12.2 g, 50 mmol) was added. The resulting mixture was stirred for 24 hours at room temperature and concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with water and brine. The aqueous phase was extracted three times with ethyl acetate. The combined organic layers were dried over MgSO4 and evaporated to afford crude product 502 (12.1 g, 79.5%). LC-MS: 276(M+1), 1HNMR(DMSO- </6)deltal.26(t, J=7.2 Hz, 3H), 4.17(q, Ji=7.2 Hz, J2=7.2Hz. 2H), 5.98(s,IH), 6.91(s, IH), 7.68(d, J=9.0Hz, 2H), 8.13(d, J=9.0Hz,2H), 11.10(s,lH).

References: [1]Patent: WO2008/33747,2008,A2 .Location in patent: Page/Page column 264.

46
[ 67-56-1 ]
[ 50551-10-5 ]
[ 57508-48-2 ]
[ 103173-54-2 ]

References: [1]Tetrahedron,2009,vol. 65,p. 757 - 764.

47
[(Z)-3-dimethylamino-2-phenylmethoxyprop-2-enylidene]dimethylazanium hexafluorophosphate [ No CAS ]
[ 57508-48-2 ]
[ 132260-01-6 ]

References: [1]Tetrahedron,2009,vol. 65,p. 757 - 764.

48
[ 1114830-09-9 ]
[ 57508-48-2 ]
[ 132260-01-6 ]
[ 132260-02-7 ]

References: [1]Tetrahedron,2009,vol. 65,p. 757 - 764.

49
[ 1114830-09-9 ]
[ 57508-48-2 ]
[ 75-36-5 ]
[ 132260-01-6 ]
[ 1114830-12-4 ]

References: [1]Tetrahedron,2009,vol. 65,p. 757 - 764.

50
[ 57508-48-2 ]
[ 99-73-0 ]
[ 1057142-91-2 ]

Yield	Reaction Conditions	Operation in experiment
61%		General procedure: The following is representative: <strong>[57508-48-2]ethyl 3-amino-3-iminopropanoate hydrochloride</strong> (3) (8.3 g, 50.0 mmol) and NaOEt (5.1 g, 75.0 mmol) were dissolved in abs. EtOH at 0 C and stirred for 20 min under argon. The mixture was heated to 60 C, and 2-bromo-1-phenylethanone (4b) (5.0 g, 25.0 mmol) was added portion wise over 5 min. After 1.5 h the mixture was cooled to 20 C and the solvent was evaporated under reduced pressure. The residue was diluted with distilled water (20 mL) and extracted with EtOAc (3 × 80 mL). The organic layer was washed with water (3 × 20 mL) and brine (3 × 20 mL). The combined water fractions were back extracted with EtOAc (2 × 20 mL). The organic phases were dried over MgSO4, and the solvent was evaporated under reduced pressure. Purification was by silica-gel column chromatography (EtOAc/n-pentane, 7/3).
		10 Mmol carbamimidoylacetic acid ethyl ester hydrochloride (Chem. Pharm. Bull. 1995, 43(5), 788-796) was suspended in ethanol, purged with argon, and 1.5 mL triethylamine was added. The mixture was cooled to 0 C., 10 mmol NaOEt was added, purged with argon, and stirred at 0 C. for 15 min. 10 Mmol 2-Bromo-1-(4-bromo-phenyl)-ethanone was added and the mixture was agitated at room temperature over night. After complete evaporation, the residue was suspended in ethyl acetate, filtered, and washed with ethyl acetate. The filtrate was evaporated and purified by flash chromatography. 3 Mmol of 2-amino-5-(4-bromo-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester thus obtained was heated under Ar in a mixture of 6 mL formamide, 3 mL DMF, and 1.5 mL formic acid at 150 C. for 16 h. After cooling to room temperature, the mixture was diluted with 10 mL isopropanol and the solid product was collected by filtration. 6-(4-Bromo-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol was chlorinated by heating in phosphorus oxychloride at 100 C. over night The reaction mixture was poured on ice and the product collected by filtration.

References: [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 6002 - 6014.
[2]Patent: US2005/153989,2005,A1 .Location in patent: Page/Page column 47.

51
[ 57508-48-2 ]
[ 104554-98-5 ]
ethyl-2-amino-(2,5-dimethoxybenzyl)-1H-pyrrole-3-carboxylate [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3575 - 3587.

52
[ 57508-48-2 ]
[ 651358-38-2 ]
[ 1234201-59-2 ]

References: [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3575 - 3587.

53
[ 57508-48-2 ]
[ 651358-40-6 ]
[ 1234201-61-6 ]

References: [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3575 - 3587.

54
[ 57508-48-2 ]
[ 105-36-2 ]
[ 1236764-06-9 ]

Yield	Reaction Conditions	Operation in experiment
		Reference Example 5 Ethyl 2-amino-5-oxo-4,5-dihydro-1H-pyrrol-3-carboxylate; Ethyl 3-amino-3-iminopropanoate hydrochloride (3 g) obtained by a method described in a published document, Chemical and Pharmaceutical Bulletin (Chem. Pharm. Bull.), Vol. 43, p. 788 (1995), or a method pursuant to thereto, was suspended in acetonitrile (90 ml), and triethylamine (6.27 ml) and ethyl bromoacetate (3.31 g) were added sequentially to this suspension. The resulting mixture was stirred for one hour at room temperature. Ethyl acetate (180 ml) was added to the reaction mixture liquid and precipitates were filtered. Then, the filtrate was concentrated under reduced pressure to obtain an orange-colored oily substance. This oily substance was dissolved in ethanol (90 ml), and a 20% sodium ethoxide-ethanol solution (15.3 g) was added thereto. Then, the resulting mixture was stirred for 30 minutes at room temperature. Acetic acid (3.09 ml) was added thereto, and then the reaction mixture liquid was concentrated under reduced pressure to obtain an orange-colored crude product. A saturated aqueous solution of sodium hydrogen carbonate was added to the crude product, and the mixture was salted out, and then was extracted with a mixed solvent of 30% tetrahydrofuran/ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain an orange-colored crude solid. This crude solid was purified by chromatography, and thus the title compound (1.22 g) was obtained as a yellowish white solid.1H NMR (300 MHz, DMSO-d6) delta ppm 1.16 (3H, t, J=7.2 Hz), 3.03 (2H, s), 4.01 (2H, q, J=7.2 Hz), 6.75 (2H, br. s.), 10.01 (1H, br. s.).

References: [1]Patent: US2010/190747,2010,A1 .Location in patent: Page/Page column 38.

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Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
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
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
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
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
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

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CAS No.: 57508-48-2

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CAS No.: 57508-48-2

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[ 57508-48-2 ] Synthesis Path-Downstream 1~54

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