[ CAS No. 52328-05-9 ] {[proInfo.proName]}

Name: 52328-05-9|O-Methylisourea hemisulfate|98.5%
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Quality Control of [ 52328-05-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 52328-05-9 ]

Product Details of [ 52328-05-9 ]

CAS No. :	52328-05-9	MDL No. :	MFCD00040594
Formula :	C₄H₁₄N₄O₆S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QSCPQKVWSNUJLJ-UHFFFAOYSA-N
M.W :	246.24	Pubchem ID :	11357018
Synonyms :

Calculated chemistry of [ 52328-05-9 ]

Physicochemical Properties

Num. heavy atoms :	15
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.5
Num. rotatable bonds :	2
Num. H-bond acceptors :	8.0
Num. H-bond donors :	6.0
Molar Refractivity :	52.44
TPSA :	201.18 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-9.3 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.21
Log Po/w (XLOGP3) :	-2.11
Log Po/w (WLOGP) :	-0.52
Log Po/w (MLOGP) :	-2.66
Log Po/w (SILICOS-IT) :	-0.77
Consensus Log Po/w :	-1.17

Druglikeness

Lipinski :	1.0
Ghose :	None
Veber :	1.0
Egan :	1.0
Muegge :	4.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	0.09
Solubility :	306.0 mg/ml ; 1.24 mol/l
Class :	Highly soluble
Log S (Ali) :	-1.59
Solubility :	6.38 mg/ml ; 0.0259 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	0.39
Solubility :	607.0 mg/ml ; 2.47 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	3.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.27

Safety of [ 52328-05-9 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 52328-05-9 ]

* 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 [ 52328-05-9 ]
Downstream synthetic route of [ 52328-05-9 ]

[ 52328-05-9 ] Synthesis Path-Upstream 1~5

1
[ 76064-23-8 ]
[ 52328-05-9 ]
[ 3289-47-2 ]

Reference： [1] Patent: CN103896859, 2016, B, . Location in patent: Paragraph 0010; 0014

2
[ 52328-05-9 ]
[ 645-36-3 ]
[ 1450-93-7 ]

Reference： [1] Tetrahedron Letters, 2002, vol. 43, # 4, p. 593 - 595

3
[ 52328-05-9 ]
[ 22483-09-6 ]
[ 1450-93-7 ]

Reference： [1] Tetrahedron Letters, 2002, vol. 43, # 4, p. 593 - 595

4
[ 52328-05-9 ]
[ 90905-32-1 ]

Reference： [1] Journal of Organic Chemistry, 2005, vol. 70, # 5, p. 1771 - 1779

5
[ 52328-05-9 ]
[ 105-56-6 ]
[ 186435-66-5 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium In methanol; water	Synthesis of 6-amino-2-methoxy-4-pyrimidone, Compound a The protocol for synthesizing compound a in the above schematic diagram was that basically as described by W. Pfleiderer (Chem. Ber., 90: 2272 (1957)). Sodium (15 g, 652 mmol) was dissolved, in small portions, in 200 ml methanol. O-Methylisourea hemisulfate (30.6 g, 248 mmol) and ethyl cyanoacetate (30 g, 265 mmol) were added to the solution. The mixture was stirred at reflux for 4.5 hours (h). The mixture was filtered, and the solid was washed carefully with methanol. The combined filtrates were evaporated to dryness, and the white solid residue was dissolved in 300 ml of hot water. After neutralization with acetic acid to pH 7, the solid was filtered, washed with water, and dried to give 28 g (80percent) of product as a white solid.

Reference： [1] Patent: US2003/181719, 2003, A1,

[ 52328-05-9 ] Synthesis Path-Downstream 1~69

1
[ 55841-04-8 ]
[ 52328-05-9 ]
[ 60870-62-4 ]

Reference： [1]Journal of Heterocyclic Chemistry,1976,vol. 13,p. 761 - 764

2
[ 55841-04-8 ]
[ 52328-05-9 ]
[ 60870-60-2 ]

Reference： [1]Journal of Heterocyclic Chemistry,1976,vol. 13,p. 761 - 764

3
[ 462-94-2 ]
[ 52328-05-9 ]
[ 18431-52-2 ]

Reference： [1]Phytochemistry,1973,vol. 12,p. 2691 - 2695

4
[ 1758-80-1 ]
[ 52328-05-9 ]
[ 14191-90-3 ]

Reference： [1]Hoppe-Seyler's Zeitschrift fur Physiologische Chemie,1975,vol. 356,p. 839 - 844

5
[ 59892-34-1 ]
[ 52328-05-9 ]
[ 61640-58-2 ]

Reference： [1]Chemische Berichte,1976,vol. 109,p. 3255 - 3261

6
[ 62773-05-1 ]
[ 52328-05-9 ]
1-((Z)-1-Heptafluoropropyl-1,3-dihydroxy-4,4-dimethyl-pent-2-enyl)-2-methyl-isourea [ No CAS ]

Reference： [1]Archiv der Pharmazie,1977,vol. 310,p. 56 - 64

7
[ 21753-19-5 ]
[ 52328-05-9 ]
[ 3476-23-1 ]

Reference： [1]Hoppe-Seyler's Zeitschrift fur Physiologische Chemie,1975,vol. 356,p. 839 - 844

8
[ 52328-05-9 ]
[ 66180-39-0 ]
[ 66180-38-9 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,1978,vol. 28,p. 235 - 241

9
[ 52133-67-2 ]
[ 52328-05-9 ]
[ 90057-07-1 ]

Reference： [1]Liebigs Annalen der Chemie,1984,vol. 1984,p. 273 - 282

10
[ 52328-05-9 ]
[ 62414-75-9 ]
[ 77049-61-7 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1981,vol. 29,p. 1838 - 1842

11
[ 52328-05-9 ]
[ 140175-93-5 ]
[ 140176-04-1 ]

Reference： [1]Journal of Organic Chemistry,1992,vol. 57,p. 2526 - 2528

12
[ 52328-05-9 ]
[ 87663-03-4 ]
[ 147452-34-4 ]

Reference： [1]Archiv der Pharmazie,1992,vol. 325,p. 761 - 767

13
[ 52328-05-9 ]
[ 98612-57-8 ]
[ 117861-37-7 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 391 - 396

14
[ 52328-05-9 ]
[ 99733-17-2 ]
[ 99733-16-1 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 391 - 396

15
[ 52328-05-9 ]
[ 622-59-3 ]
[ 132533-30-3 ]

Reference： [1]Synthesis,1990,p. 1020 - 1023

16
[ 52328-05-9 ]
[ 108-91-8 ]
[ 6331-57-3 ]

Reference： [1]Archiv der Pharmazie,1992,vol. 325,p. 761 - 767

17
[ 52328-05-9 ]
[ 2131-55-7 ]
[ 133252-65-0 ]

Reference： [1]Synthesis,1990,p. 1020 - 1023

18
[ 52328-05-9 ]
[ 14152-97-7 ]
[ 77049-60-6 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1981,vol. 29,p. 1838 - 1842

19
[ 52328-05-9 ]
[ 1003-03-8 ]
[ 45715-47-7 ]

Reference： [1]Archiv der Pharmazie,1992,vol. 325,p. 761 - 767

20
[ 52328-05-9 ]
[ 765-30-0 ]
[ 168627-33-6 ]

Reference： [1]Archiv der Pharmazie,1992,vol. 325,p. 761 - 767

21
[ 52328-05-9 ]
[ 1985-12-2 ]
[ 132533-31-4 ]

Reference： [1]Synthesis,1990,p. 1020 - 1023

22
[ 52328-05-9 ]
[ 161694-48-0 ]
[ 161694-49-1 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1996,p. 1287 - 1297
[2]Journal of the Chemical Society. Chemical communications,1995,p. 283 - 286

23
[ 52328-05-9 ]
(9E)-(+/-)-<6-(Benzoyloxymethylene)-3-methyl-7-oxobicyclo<3.3.1>non-3-en-1-yl>carbamic acid methyl ester [ No CAS ]
(11E)-(+/-)-(11-Ethylidene-5,8,9,10-tetrahydro-7-methyl-5,9-methanocycloocta<d>pyrimidin-9-yl)carbamic acid methyl ester [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1996,p. 1287 - 1297
[2]Journal of the Chemical Society. Chemical communications,1995,p. 283 - 286

24
[ 52328-05-9 ]
[ 176214-18-9 ]
2-Methoxy-5-trifluoromethyl-pyrimidine [ No CAS ]

Reference： [1]Tetrahedron Letters,1996,vol. 37,p. 1829 - 1832

25
[ 52328-05-9 ]
[ 645-36-3 ]
[ 1450-93-7 ]

Reference： [1]Tetrahedron Letters,2002,vol. 43,p. 593 - 595

26
[ 52328-05-9 ]
[ 22483-09-6 ]
[ 1450-93-7 ]

Reference： [1]Tetrahedron Letters,2002,vol. 43,p. 593 - 595

27
[ 4620-47-7 ]
[ 52328-05-9 ]
[ 637363-32-7 ]

Reference： [1]Chemistry - A European Journal,2003,vol. 9,p. 4997 - 5010

28
[ 52328-05-9 ]
[ 698386-24-2 ]
6-(1'-deoxy-2',3':4',5'-di-O-isopropylidene-D-xylityl)-5-fluoro-2-methoxy-4-(perfluoroethyl)pyrimidine [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2004,p. 1444 - 1454

29
[ 52328-05-9 ]
(E)-1-((3aR,6S,6aR)-6-Benzyloxy-2,2-dimethyl-tetrahydro-furo[2,3-d][1,3]dioxol-5-yl)-3,4,5,5,6,6,6-heptafluoro-hex-3-en-2-one [ No CAS ]
6-(3'-O-benzyl-5'-deoxy-1',2'-O-isopropylidene-β-L-arabinofuranosyl)-5-fluoro-2-methoxy-4-(perfluoroethyl)pyrimidine [ No CAS ]
6-(3'-O-benzyl-5'-deoxy-1',2'-O-isopropylidene-α-D-xylofuranosyl)-5-fluoro-2-methoxy-4-(perfluoroethyl)pyrimidine [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2004,p. 1444 - 1454

30
2-iminiomethylvinamidinium trichloride [ No CAS ]
[ 52328-05-9 ]
[ 90905-32-1 ]

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 1771 - 1779

31
[ 52328-05-9 ]
[ 108-24-7 ]
C₄H₈N₂O₂*H₂O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; at 30℃;	A suspension of the 0-methyl isourea sulfate (1.23 g, 10 mmol) in acetic anhydride (20 [ML)] and pyridine (2.4 ml, [30] mmol) was stirred overnight at 30C under N2. The volatiles were then evaporated and methanol was added. A white solid was only partially soluble and was removed by filtration and analysed.

Reference： [1]Patent: WO2003/102592,2003,A2 .Location in patent: Page 20

32
[ 52328-05-9 ]
[ 58-85-5 ]
C₁₂H₂₀N₄O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide);	A suspension of biotin (244 mg, 1 mmol), [O-METHYL] isourea sulfate (123 mg, 1 mmol) and EDC (384 mg, 2 mmol) in diisopropylethylamine (0.18 ml, [L] mmol) and DMF (19 ml) was stirred overnight. The reaction mixture was then evaporated using a rotary evaporator with a bath temperature [OF 40C] and a high-vacuum pump. After evaporation, methanol was added and a solution formed. This material was subjected to a silica gel column chromatography using 10% methanol in DCM as eluent. The product eluted from the column very slowly. A small amount of product was isolated whose'H NMR spectrum (in both d4 methanol and d6 DMSO) is consistent with the desired product although some impurity peaks are visible. An attempt was made to further purify this product by recrystallisation from methanol. The product was previously soluble in methanol but upon addition of methanol and warming a portion of the material remained insoluble; [THE'H] NMR spectrum of this material in d6 DMSO shows it to be the biotin adduct of the urea (Figure 10, compound B).

Reference： [1]Patent: WO2003/102592,2003,A2 .Location in patent: Page 19; 8/14

33
[ 52328-05-9 ]
[ 109-52-4 ]
[ 847355-27-5 ]

Yield	Reaction Conditions	Operation in experiment
42%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide);	A suspension of valeric acid (0.22 ml, 2 mmol), [O-METHYL] isourea sulfate (246 g, 2 mmol) and EDC (0.77 g, 4 mmol) in diisopropylethulamine (0.36 ml, 24 mmol) and DMF (20 ml) was stirred overnight. The reaction mixture was then evaporated using a rotary evaporator with a bath temperature of [35C] and a high-vacuum pump. After evaporation, the crude product was dissolved in a mixture of DCM, methanol and acetone and added to a silica gel column containing DCM. The desired product eluted in the first three fractions and was fairly pure (as demonstrated by nmr spectroscopy). An attempt was made to re-purify this material by column chromatography (eluent = [DCM/METHANOL)] but no material corresponding to the product was isolated.The reaction was repeated on a larger scale: a suspension of valeric acid (0.44 [ML,] 4 mmol), [O-METHYL] isourea sulfate (492 mg, 4 mmol) and EDC (1.53 g, 8 mmol) in diisopropylethylamine (0.72 ml, 4 mmol) and DMF (150 ml) was stirred overnight. The reaction mixture was then evaporated using a rotary evaporator with a bath temperature of [35 C] and a high-vacuum pump. After evaporation, dioxane was added and the reaction mixture was filtered, thus removing [UNREACTED] [O-METHYL] isourea sulfate. The dioxane soluble material was purified by silica gel column chromatography using dioxane as eluent. The product was obtained as an off-white solid 0.27 g (42%) and was not as pure as the material previously isolated.

Reference： [1]Patent: WO2003/102592,2003,A2 .Location in patent: Page 21-22

34
[ 66129-60-0 ]
[ 52328-05-9 ]
[ 862838-05-9 ]

Yield	Reaction Conditions	Operation in experiment
46%	With sodium hydrogencarbonate; In 1-methyl-pyrrolidin-2-one; at 80℃; for 12h;	b) Ethyl 4-phenyl-2-methoxypyrimidine-5-carboxylate (XI) Ar = phenyl, X = MeO; The mixture of ethyl 2-benzoyl-3- (dimethylamino) acrylate (57.9g, 234.12 mmol), O-methylisocarbamide sulphate (35g, 284.68 mol), sodium hydrogencarbonate (23.9g, 284.68 mmol) and N-methylpyrrolidinone (647 ml) is heated at 80 C for 12 hours. To the reaction mixture ethyl acetate and water are added, the organic phase is washed with hydrochloric acid solution, dried over sodium sulphate, evaporated in vacuum, chromatographed on silicagel using dichloromethane-heptane solvent mixture as eluent. 28 g (46 %) of the title compound was obtained. LC/MS [MH+] 259.1 (Cl4Hl4N203 258.276)

Reference： [1]Patent: WO2005/75458,2005,A1 .Location in patent: Page/Page column 53

35
[ 52328-05-9 ]
[ 105-56-6 ]
[ 186435-66-5 ]

Yield	Reaction Conditions	Operation in experiment
28 g (80%)	With sodium; In methanol; water;	Synthesis of 6-amino-2-methoxy-4-pyrimidone, Compound a The protocol for synthesizing compound a in the above schematic diagram was that basically as described by W. Pfleiderer (Chem. Ber., 90: 2272 (1957)). Sodium (15 g, 652 mmol) was dissolved, in small portions, in 200 ml methanol. O-Methylisourea hemisulfate (30.6 g, 248 mmol) and ethyl cyanoacetate (30 g, 265 mmol) were added to the solution. The mixture was stirred at reflux for 4.5 hours (h). The mixture was filtered, and the solid was washed carefully with methanol. The combined filtrates were evaporated to dryness, and the white solid residue was dissolved in 300 ml of hot water. After neutralization with acetic acid to pH 7, the solid was filtered, washed with water, and dried to give 28 g (80%) of product as a white solid.

Reference： [1]Patent: US2003/181719,2003,A1

36
[ 29427-58-5 ]
[ 929-17-9 ]
[ 123042-88-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium; In methanol; water;	TLC (n-butanol:acetic acid:water=4:1:1 v/v) Rf=0.3. The 7-guanidinoheptanoic acid N-hydroxysuccinimide ester hydrochloride used above was synthesised in the following way: 50.0 g (0.344 mols) of 7-aminoheptanoic acid and 63.5 g (0.514 mol) of O-methylisourea sulfate were dissolved in 250 ml of 50% aqueous methanol (v/v). To the solution was added dropwise a solution of 34.3 g (0.858 mol) of sodium hdyroxide in 400 ml of water. Then, the mixture was heated overnight under reflux. The reaction mixture was concentrated to about a half volume under reduced pressure followed by cooling the concentrate to precipitate white crystals. The crystals were collected by filtration, and dried to give 42.6 g (yield: 66.1%) of 7-guanidinoheptanoic acid. NMR (D2 O+DCl): delta=1.0-2.0 (b, 9H), 2.2-2.6 (m, 2H), 3.0-3.3 (m, 2H).

Reference： [1]Patent: US4529549,1985,A

37
2-cyanoethyl 2-[(3,4-difluorophenyl)methylene]-3-oxo-4-methoxybutyrate [ No CAS ]
[ 52328-05-9 ]
5-(2-cyanoethoxycarbonyl)-1,6-dihydro-2-methoxy-4-methoxymethyl-6-(3,4-difluorophenyl)pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2-(Dimethylamino)pyridine; In ethanol;	c) 5-(2-Cyanoethoxycarbonyl)-1,6-dihydro-2-methoxy-4-methoxymethyl-6-(3,4-difluorophenyl)pyrimidine. A suspension of 2-cyanoethyl 2-[(3,4-difluorophenyl)methylene]-3-oxo-4-methoxybutyrate (29 g, 0.094 mol), <strong>[52328-05-9]O-methylisourea hemisulfate</strong> (21 g, 0.121 mol, 1.3 eq.), dimethylaminopyridine (29.67 g, 0.243 mol, 2.5 eq.) in ethanol (400 mL) was stirred at 50-55 C. for 6 h. The solvent was evaporated from the combined filtrates and the residue was purified by column chromatography (SiO2, EtOAc/hexane, 10%-30%) to get 5-(2-cyanoethoxycarbonyl)-1,6-dihydro-2-methoxy-4-methoxymethyl-6-(3,4-difluorophenyl)pyrimidine as a pale yellow oil (10.5 g, 31%).
	With 2-(Dimethylamino)pyridine; In ethanol;	c) 5-(2-Cyanoethoxycarbonyl)-1,6-dihydro-2-methoxy-4-methoxymethyl-6-(3,4-difluorophenyl)pyrimidine. A suspension of 2-cyanoethyl 2-[(3,4-difluorophenyl)methylene]-3-oxo-4-methoxybutyrate (29 g, 0.094 mol), <strong>[52328-05-9]O-methylisourea hemisulfate</strong> (21 g, 0.121 mol, 1.3 eq.), dimethylaminopyridine (29.67 g, 0.243 mol, 2.5 eq.) in ethanol (400 mL) was stirred at 50-55 C. for 6 h. The solvent was evaporated from the combined filtrates and the residue was purified by column chromatography (SiO2, EtOAc/hexane, 10%-30%) to get 5-(2-cyanoethoxycarbonyl)-1,6-dihydro-2-methoxy-4-methoxymethyl-6-(3,4-difluorophenyl)pyrimidine as a pale yellow oil (10.5 g, 31%).

Reference： [1]Patent: US6268369,2001,B1
[2]Patent: US6245773,2001,B1

38
[ 324558-30-7 ]
[ 52328-05-9 ]
[ 6674-22-2 ]
3-methyl-2,4-dioxo-6-(1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide;	EXAMPLE 57 3-Methyl-2,4-dioxo-6-(1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile In analogy to the procedure described in example 17 the Z and/or E 2-cyano-3-methylsulfanyl-3-(1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-acrylic acid ethyl ester [example 13 a)] was treated with <strong>[52328-05-9]O-methylisourea hemisulfate</strong> and 1,8-diazabicyclo[5.4.0]undec-7-en in N,N-dimethylformamide at 100 C. to yield the 3-methyl-2,4-dioxo-6-(1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile as light yellow solid; m.p. >200 C.; MS: [M+H]+=297.

Reference： [1]Patent: US6218385,2001,B1

39
[ 179482-45-2 ]
[ 52328-05-9 ]
[ 179482-46-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In ethanol;	b) 5-Methoxycarbonyl-1,6-dihydro-2-methoxy-4-methoxymethyl-6-(3,4-difluorophenyl)pyrimidine. A suspension of methyl 2-[(3,4-difluorophenyl) methylene]-3-oxo-4-methoxybutyrate (7.50 g, 27.75 mmol), <strong>[52328-05-9]O-methylisourea hemisulfate</strong> (7.17 g, 41.63 mmol, 1.5 eq.), sodium bicarbonate (6.99 g, 83.25 mmol, 3 eq.) in ethanol (400 mL) was stirred at 50-55 C. for 6 h. The solvent was evaporated from the combined filtrates and the residue was purified by column chromatography (SiO2, EtOAc/hexane, 10%-30%) to get 5-methoxycarbonyl-1,6-dihydro-2-methoxy-4-methoxymethyl-6-(3,4-difluorophenyl)pyrimidine as a pale yellow oil (4.3 g, 47%).

Reference： [1]Patent: US6268369,2001,B1

40
benzyl 2-[(2,4-difluorophenyl)methylene]-3-oxopentanoate [ No CAS ]
[ 52328-05-9 ]
[ 191353-81-8 ]

Yield	Reaction Conditions	Operation in experiment
42%	With sodium hydrogencarbonate; In ethanol;	b 5-(Benzyloxycarbonyl)-1,6-dihydro-2-methoxy-4-ethyl-6-(2,4-difluorophenyl)pyrimidine (Scheme 2; Step D) A suspension of benzyl 2-[(2,4-difluorophenyl)methylene]-3-oxopentanoate (80.0 g, 0.241 mol), <strong>[52328-05-9]O-methylisourea hemisulfate</strong> (63.8 g, 0.362 mol, 1.5 eq.), NaHCO3 (60.48 g, 0.72 mol) in ethanol (800 mL) was stirred at 60-70 C. for 20 h. After cooling to room temperature, the mixture was filtered, and the solid was washed with ethanol (200 mL). The solvent was evaporated from the combined filtrates and the residue was purified by column chromatography (SiO2, EtOAc/Hexane, 10%-30%) to yield 5-(benzyloxycarbonyl)-1,6-dihydro-2-methoxy-4-ethyl-6-(2,4-difluorophenyl) pyrimidine as a pale yellow oil (39 g, 42%).
	With sodium hydrogencarbonate; In ethanol;	d) 5-(Benzyloxycarbonyl)-1,6-dihydro-2-methoxy-4-ethyl-6-(2,4-difluorophenyl)pyrimidine. A suspension of benzyl 2-[(2,4-difluorophenyl)methylene]-3-oxopentanoate (80.0 g, 0.241 mol), <strong>[52328-05-9]O-methylisourea hemisulfate</strong> (63.8 g, 0.362 mol, 1.5 eq.), NaHCO3 (60.48 g, 0.72 mol) in ethanol (800 mL) was stirred at 60-70 C. for 20 h. After cooling to room temperature, the mixture was filtered, and the solid was washed with ethanol (200 mL). The solvent was evaporated from the combined filtrates and the residue was purified by column chromatography (SiO2, EtOAc/Hexane, 10%-30%) to get 5-(benzyloxycarbonyl)-1,6-dihydro-2-methoxy-4-ethyl-6-(2,4-difluorophenyl)pyrimidine as a pale yellow oil (39 g, 42%).

Reference： [1]Patent: US6172066,2001,B2
[2]Patent: US6245773,2001,B1

41
[ 52328-05-9 ]
methyl 2-[(3,4-difluorophenyl)-methylene]-3-oxo-4-methoxybutyrate [ No CAS ]
[ 179482-46-3 ]

Yield	Reaction Conditions	Operation in experiment
47%	With sodium hydrogencarbonate; In ethanol;	b 5-Methoxycarbonyl-1,6-dihydro-2-methoxy-4-methoxymethyl-6-(3,4-difluorophenyl)pyrimidine (Scheme 2; Step D) A suspension of methyl 2-[(3,4-difluorophenyl)methylene]-3-oxo-4-methoxybutyrate (7.50 g, 27.75 mmol), <strong>[52328-05-9]O-methylisourea hemisulfate</strong> (7.17 g, 41.63 mmol, 1.5 eq.), and sodium bicarbonate (6.99 g, 83.25 mmol, 3 eq.) in ethanol (400 mL) was stirred at 50-55 C. for 6 h. The solvent was evaporated from the combined filtrates and the residue was purified by column chromatography (SiO2, EtOAc/hexane, 10%-30%) to give 5-methoxycarbonyl-1,6-dihydro-2-methoxy-4-methoxymethyl-6-(3,4-difluorophenyl)pyrimidine as a pale yellow oil (4.3 g, 47%).
	With sodium hydrogencarbonate; In ethanol;	b) 5-Methoxycarbonyl-1,6-dihydro-2-methoxy-4-methoxymethyl-6-(3,4-difluorophenyl)pyrimidine. A suspension of methyl 2-[(3,4-difluorophenyl)methylene]-3-oxo-4-methoxybutyrate (7.50 g, 27.75 mmol), <strong>[52328-05-9]O-methylisourea hemisulfate</strong> (7.17 g, 41.63 mmol, 1.5 eq.), sodium bicarbonate (6.99 g, 83.25 mmol, 3 eq.) in ethanol (400 mL) was stirred at 50-55 C. for 6 h. The solvent was evaporated from the combined filtrates and the residue was purified by column chromatography (SiO2, EtOAc/hexane, 10%-30%) to get 5-methoxycarbonyl-1,6-dihydro-2-methoxy-4-methoxymethyl-6-(3,4-difluorophenyl)pyrimidine as a pale yellow oil (4.3 g, 47%).

Reference： [1]Patent: US6172066,2001,B2
[2]Patent: US6245773,2001,B1

42
[ 52328-05-9 ]
[ 137860-26-5 ]
[ 1028725-27-0 ]

Yield	Reaction Conditions	Operation in experiment
16%	With sodium methylate; In methanol; at 1 - 30℃;	A solution of methyl imidocarbamate sulfate (10 g) , 28% sodium methoxide (26 mL) and ethyl 2- [ (2' -cyanobiphenyl-4- yl) methyl] -3-xohexanoate (15.8 g) in methanol (100 mL) was stirred overnight at room temperature. The solvent was evaporated under reduced pressure, and water and acetic acid were added. The precipitated solid was collected by filtration, washed with water and diethyl ether to give the title compound (2.62 g, 16%) as a colorless solid.1H NMR (300 MHz, DMSO-d6) delta 0.86 (3H, t, J = 7.2), 1.46-1.64 (2H, m) , 2.46 (2H, t, J = 7.2), 3.82 (2H, s) , 3.86 (3H, s) , 7.32 (2H, d, J = 8.4), 7.47 (2H, d, J = 8.4), 7.52-7.63 (2H, m) , 7.72-7.82 (IH, m) , 7.92 (IH, d, J= 6.6), 12.21 (IH, br)

Reference： [1]Patent: WO2008/62905,2008,A2 .Location in patent: Page/Page column 182

43
4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)isoxazol-3-yl]-2-methylbenzoyl chloride [ No CAS ]
[ 52328-05-9 ]
[ 1056459-47-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In acetonitrile; at 20℃; for 1.5h;	[Synthetic Example 2] N-[Amino(methoxy) methylidene]-4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methyl benzoic acid amide (compound of the present invention No.2-003) To a solution of 1.00 g of 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methylbenzoyl-chloride synthesised in Process 4 of Synthetic Example 1 in 20 mL of acetonitrile, 0.85 g of O-methylisourea sulfate and 1.26 g of potassium carbonate were added and the resultant mixture was stirred at room temperature for 1.5 hours. After the completion of the reaction, the insoluble substance was filtered off and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography eluding with ethyl acetate-hexane (1:1) to obtain 0.40 g of the objective substance as a yellow resin-state substance. 1H NMR (CDCl3, Me4Si, 300 MHz) delta 9.20 (bs, 1H), 8.09 (d, J=8.4 Hz, 1H), 7.4-7.6 (m, 5H), 5.58 (bs, 1H), 4.10 (d, J=17.4 Hz, 1H), 3.93 (s, 3H), 3.71 (d, J=17.4, 1H), 2.65 (s, 3H).

Reference： [1]Patent: EP2151437,2010,A1 .Location in patent: Page/Page column 90

44
[ 52328-05-9 ]
[ 372-31-6 ]
[ 175354-56-0 ]

Yield	Reaction Conditions	Operation in experiment
		5.61 g of O-methylisouronium sulfate and 3 g of 4,4,4- trifluoro-3-oxo-butanoic acid ethyl ester were added. This mixture was stirred at 80C for 20 hours. The reaction mixture was left standing to cool and then concentrated. To the residue, 10% hydrochloric acid was added. A precipitated crystal was collected by filtration and then washed with water to obtain 1.5 g of 2-methoxy-6- trifluoromethylpyrimidin-4-ol . 2-methoxy-6-trifluoromethylpyrimidin-4-ol1H-NMR (DMSO-d6) : 3.93(s,3H) , 6.50(s,lH) , 13.00(bs,lH)

Reference： [1]Patent: WO2010/134478,2010,A1 .Location in patent: Page/Page column 177; 178

45
[ 29427-58-5 ]
[ 555-16-8 ]
[ 94-02-0 ]
[ 1315574-50-5 ]

Yield	Reaction Conditions	Operation in experiment
88%		General procedure: Compounds 3a-j were prepared according to the literature procedure.4c A typical procedure is as follows: A solution of ethyl 3-phenyl-3-oxopropanoate (576 mg, 3 mmol), O-methylisourea hydrogen sulfate (516 mg, 3 mmol), and 4-nitrobenzaldehyde (453 mg, 3 mmol) in 3 mL of dry DMF under nitrogen at room temperature was treated with sodium bicarbonate (756 mg, 9 mmol) and heated at 75 C for 3-4 h. The reaction mixture was cooled to room temperature, then transferred into water (7 mL) with ice-bath cooling over 1 h, during, which time the product solidified out from the solution. Stirring was continued at room temperature for >3 h, and the product was filtered. The cake was washed with water (10 mL) and dried under vacuum until constant weight was obtained. Compound 3j (800 mg, 2.1 mmol, 70%) was obtained as a pale-yellow solid. Purification was accomplished by chromatography after the standard extractive workup with EtOAc when the product is not sufficiently crystalline. A mixture of dihydropyrimidine 3a (290 mg, 1 mmol), NHPI (16 mg, 10 mol %), and Co(OAc)2·4H2O (1 mg, 0.5 mol %) was placed in a 25 mL three-necked flask in (CH2Cl)2 (4 mL) and stirred at 80 C under oxygen atmosphere for 1 h. When the starting materials were consumed completely monitored by TLC, the reaction mixture was concentrated by vacuum and then the product was isolated by silica gel column chromatography to give white oil 4a 278 mg (yield: 97%).

Reference： [1]Tetrahedron,2011,vol. 67,p. 5615 - 5620

46
[ 18333-00-1 ]
[ 52328-05-9 ]
[ 1374216-08-6 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 2398 - 2401

47
[ 1392049-29-4 ]
[ 52328-05-9 ]
[ 1392049-89-6 ]

Yield	Reaction Conditions	Operation in experiment
62%	With potassium carbonate; In acetonitrile; for 16h;Reflux;	To a solution of ethyl (7E) -[(dimethylamino)methylidene]-A/-methoxy-A/,1-dimethyl-8-oxo-1 , 4,5,6,7,8- hexahydrocyclohepta[c]pyrazole-3-carboxamide (1.62 g, 5.3 mmol) in CH3CN (130 ml), O-methylisourea sulphate (5.22g, 21.2 mmol) and K2CO3 (3g, 22.2 mmol) were added. The reaction mixture was stirred at reflux for 16h, then it was filtered to remove salts and the solvent was evaporated. The residue was suspended in DCM and washed with water; the organic phase was dried on Na2S04, filtered and concentrated. The crude was purified by flash- chromatography in silica gel (hexane/AcOEt: 1/1) to afford 1 g (62 % yield) of the title compound as a white solid. 1H NMR (401 MHz, DMSO-d6) delta ppm 1.85 - 2.01 (m, 2 H) 2.63 - 2.70 (m, 2 H) 2.82 (t, J=7.02 Hz, 2 H) 3.71 (s, 3 H) 3.81 (s, 3 H) 3.97 (s, 3 H) 4.22 (s, 3 H) 7.36 (s, 1 H) 8.52 (s, 1 H)MS calc: 318.1561 ; MS found: 318.1553

Reference： [1]Patent: WO2012/101029,2012,A1 .Location in patent: Page/Page column 94-95

48
[ 52328-05-9 ]
[ 105-45-3 ]
[ 105-07-7 ]
[ 1333015-13-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In N,N-dimethyl-formamide;	Intermediate 4. 4-(4-Cyanophenyl)-2-methoxy-6-methyl-1,4-dihydropyrimidine-5-carboxylic acid methyl ester To a solution of 4-cyanobenzaldehyde (13.1 g, 100 mmol) in DMF (200 mL), was added sodium bicarbonate (33.4 g, 400 mmol), followed by <strong>[52328-05-9]O-methylisourea hemisulphate</strong> (14.8 g, 120 mmol) and methyl acetoacetate (12.8 g, 110 mmol). The reaction mixture was heated at 70 C. for 5 hours, then poured into water and the product was extracted into EtOAc. The organic phase was washed with water (*2) followed by brine then dried (Na2SO4) and evaporated to dryness. The resulting yellow gum was purified by silica gel chromatography eluting with diethyl ether to give the title compound as a yellow solid (12.8 g). LC-MS (Method 1): Rt=2.20 min, m/z=286 [M+H]+

Reference： [1]Patent: US2013/65913,2013,A1 .Location in patent: Paragraph 0364; 0365; 0366

49
[ 1118-84-9 ]
[ 52328-05-9 ]
[ 105-07-7 ]
[ 1333000-84-2 ]

Yield	Reaction Conditions	Operation in experiment
53%	With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 70℃;Inert atmosphere;	4-Cyanobenzaldehyde (13.1 g, 100 mmol) was dissolved in DMF (200 ml) and sodium bicarbonate (33.4 g, 400 mmol) was added, followed by <strong>[52328-05-9]O-methylisourea hemisulphate</strong> (14.8 g, 120 mmol) and allyl acetoacetate (15.06 g, 110 mmol). The mixture was heated under nitrogen at 70 C. overnight. After allowing to cool to RT, the mixture was filtered and the filtrate was evaporated. The resulting orange oil was partitioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried (Na2SO4) and evaporated. The crude product was purified by flash silica chromatography eluting with 0-30% ethyl acetate in DCM to give pure Intermediate 4 as a yellow foam. Yield: 16.8 g (53%) LC-MS (Method 1): Rt=2.18 min, m/z=312 [M+H]+

Reference： [1]Patent: US2013/150380,2013,A1 .Location in patent: Paragraph 0123; 0124; 0125; 0126

50
[ 29427-58-5 ]
[ 20542-08-9 ]
1-(N-guanidinoethyl)-4-(N-hydroxyethyl)piperazine hydrochloride [ No CAS ]

Reference： [1]Journal of the Chinese Chemical Society,2014,vol. 61,p. 341 - 344

51
α-lactalbumin [ No CAS ]
[ 52328-05-9 ]
lysine-guanidinated α-lactalbumin [ No CAS ]

Reference： [1]Rapid Communications in Mass Spectrometry,2014,vol. 28,p. 1489 - 1500

52
[ 52328-05-9 ]
papain [ No CAS ]
lysine-guanidinated papain [ No CAS ]

Reference： [1]Rapid Communications in Mass Spectrometry,2014,vol. 28,p. 1489 - 1500

53
[ 52328-05-9 ]
myoglobin [ No CAS ]
lysine-guanidinated myoglobin [ No CAS ]

Reference： [1]Rapid Communications in Mass Spectrometry,2014,vol. 28,p. 1489 - 1500

54
[ 52328-05-9 ]
bovine serum albumin [ No CAS ]
lysine-guanidinated bovine serum albumin [ No CAS ]

Reference： [1]Rapid Communications in Mass Spectrometry,2014,vol. 28,p. 1489 - 1500

55
[ 52328-05-9 ]
[ 141-97-9 ]
[ 100-52-7 ]
[ 198826-89-0 ]

Reference： [1]Green Chemistry,2014,vol. 16,p. 3752 - 3757

56
[ 52328-05-9 ]
[ 141-97-9 ]
[ 123-11-5 ]
[ 1187376-67-5 ]

Reference： [1]Green Chemistry,2014,vol. 16,p. 3752 - 3757

57
[ 52328-05-9 ]
[ 141-97-9 ]
[ 104-88-1 ]
[ 1187376-61-9 ]

Reference： [1]Green Chemistry,2014,vol. 16,p. 3752 - 3757

58
[ 76064-23-8 ]
[ 52328-05-9 ]
[ 3289-47-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium methylate; In methanol; at 60℃; for 12h;	A solution of sodium methoxide (35.7 g, 0.66 mol) and 270 mL of methanol was placed in a reaction kettle and stirred well; A solution of 3-hydroxyacrylonitrile sodium salt (27.3 g, 0.3 mol)And <strong>[52328-05-9]O-methylisourea hemisulfate</strong>(40.6 g, 0.165 mol); the temperature was raised to 60 C and the cyclization reaction was carried out for 12 hours to obtain a cyclization. The reaction solution was distilled off under methanol to give the intermediate, followed by the addition of 95 mL of the intermediate. Concentrated hydrochloric acid, heated to 70 C and heat 2 hours; heat and then add 60mL to the solution Water, and the resulting filtrate was cooled to room temperature; 10 mol / L was added dropwise to the filtrate Of the sodium hydroxide solution to adjust the pH value, when the pH is 7 ~ 7.5, the cooling to 10 ;But after the filter, washed, dried to get cytosine 29.8g, yield 89.4%HPLC content of 99.3%.

Reference： [1]Patent: CN103896859,2016,B .Location in patent: Paragraph 0010; 0014

59
[ 107-10-8 ]
[ 52328-05-9 ]
[ 23483-93-4 ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 5498 - 5508

60
[ 52328-05-9 ]
[ 109-73-9 ]
[ 3867-74-1 ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 5498 - 5508

61
[ 500011-87-0 ]
[ 52328-05-9 ]
3-bromo-N-(4-chloro-2-methyl-6-((O-methylisourea)formyl)phenyl)-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.5g	With triethylamine; In N,N-dimethyl-formamide; at 20℃;	0.5 g (1.1 mmol) of 6-chloro-2-(3-bromo-1-(3-chloro-2-pyridyl)-1H-5-pyrazolyl)-8-methyl-4H-3,1-benzoxazin-4-one was suspended in 20 mL of DMF, 0.3 g (1.2 mmol) O-methylisourea sulfate, 0.12 g (1.2 mmol) of triethylamine, Room temperature reaction overnight, the next day to clarify the solution,The reaction solution was slowly added to 20 mL of water with stirring,Slowly precipitate the solid, continue stirring 2h,Filtration, drying finished product 0.5g,

Reference： [1]Patent: CN104725348,2017,B .Location in patent: Paragraph 0039; 0040

62
[ 143-23-7 ]
[ 52328-05-9 ]
[ 13516-25-1 ]

Yield	Reaction Conditions	Operation in experiment
	In water; at 50℃; for 6h;	Bishexamethylenetriamine (1.0804 g, 5 mmol, 1 eq)withO-methylisourea sulfate (1.4825 g, 12.5 mmol, 2.4 eq)Was dissolved in H2O (7 mL)50 reaction 6h,The reaction is completed.Placed in 4 refrigerator,Precipitation of white solid,filter,Followed by ice water,Ethanol washing,Dried to give compound N, N-dihexylguanidino dimethylamine (diG6).

Reference： [1]Patent: CN107235925,2017,A .Location in patent: Paragraph 0131; 0132; 0133

63
[ 4572-03-6 ]
[ 29427-58-5 ]
C₉H₂₁N₅*(x)H₂O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	In water; at 100℃; for 24h;	General procedure: To a solution of primary amines 7a-l (2 eq) inwater (0.5 mol/L) wasadded O-methylisourea bisulfate (1 eq). Solution was stirred at 100 C for 24 h. After concentration to dryness, ethanol was addedand the residue was sonicated until apparition of a precipitate. Insome difficult cases, the suspension in ethanol was stored overnightin a freezer and triturated with cold ethanol to get a powder.Addition of a few drops of diethylether was also occasionallyneeded to induce precipitation. The solids 8a-l were collected byfiltration, washed with ethanol and dried overnight under vacuum.Due to the hygroscopicity of isolated solids, no melting points weredetermined for these series. NH signals are missing for all compoundsin 1H NMR spectra.

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 166,p. 304 - 317

64
[ 3694-57-3 ]
[ 52328-05-9 ]
C₁₁H₁₅N₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Add DMF (40L), O-methylisourea sulfate (7.5kg), sodium bicarbonate (6kg) to the reaction kettle, stir the reaction at 30-40 C for 0.5h, add1-(methylisothiocyanate)-4-methoxyanisole (21.2 kg) dissolved in N,N-dimethylformamide (5 L), stirred at 30-40 C 6- 8h, TLC traces the end of the reaction and drops at 30-40 CDiisopropyl azodicarboxylate (12.9kg), stirred at 35-45 C for 2 h after the completion of the dropwise addition, TLC followed the end of the reaction, adding purified water (180 L), precipitation of a large amount of light yellow solid, stirring and crystallization for 2-3 h, centrifugation Filtration, drying, washing the cake with water and petroleum ether, filtered and dried to give the title product (278.7 g, yield 110%).

Reference： [1]Patent: TW2018/37039,2018,A .Location in patent: Page/Page column 28; 29

65
potassium (Z)-2-cyano-2-fluoroethenolate [ No CAS ]
[ 52328-05-9 ]
[ 1993-63-1 ]

Reference： [1]European Journal of Organic Chemistry,2019,vol. 2019,p. 5519 - 5526

66
[ 620-02-0 ]
[ 52328-05-9 ]
[ 141-97-9 ]
C₁₄H₁₈N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75.7%	In N,N-dimethyl-formamide; at 75℃; for 16h;Inert atmosphere; Alkaline conditions;	Furfural (16.92 g, 153.68 mmol), O-methylisothiourea sulfate (26.46 g, 153.68 mmol) and ethyl acetoacetate (20 g, 153.68 mmol) were dissolved in anhydrous N,N-dimethylformamide (200 mL), sodium dicarbonate (19.37 g, 230.52 mmol) was added into the solution. Under nitrogen atmosphere, the reaction mixture was heated to 75C, stirred for 16 hours and then cooled down to room temperature. The reaction mixture was added into EtOAc (200 mL), washed successively by water (200 mL*3) and saturated brine (200 mL), the combined organic phases were dried over anhydrous sodium sulfate, then concentrated under reduced pressure, and the residue was purified by silica gel chromatography (PE:EtOAc=10-3:1) to give the compound 26-f (32.38 g, yield: 75.7%).

Reference： [1]Patent: EP3594216,2020,A1 .Location in patent: Paragraph 0336; 0337

67
[ 1121-60-4 ]
[ 52328-05-9 ]
[ 141-97-9 ]
C₁₄H₁₇N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	In N,N-dimethyl-formamide; at 70℃; for 3h;Inert atmosphere; Alkaline conditions;	-Pyridine carboxaldehyde (5.0 g, 46.7 mmol), O-methylisothiourea sulfate (9.64 g, 56.0 mmol) and ethyl acetoacetate (6.67 g, 51.3 mmol) were dissolved in anhydrous N,N-dimethylformamide (100 mL), then sodium dicarbonate (15.7 g, 186.8 mmmol) was added into the solution. The reaction mixture was heated to 70C under nitrogen atmosphere, stirred for 3 hours and then cooled down to room temperature. After addition of saturated brine (200 mL), a large amount of yellow suspended solids appeared, EtOAc (500 mL *2) was used for extraction, the organic phases were combined and washed by water (200 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate, then concentrated under reduced pressure, and the residue was purified by silica gel chromatography (PE:EtOAc=10:1) to give a white solid 24-f (10.2 g, yield: 79%). LC-MS (ESI): m/z =276.3 [M+H]+.

Reference： [1]Patent: EP3594216,2020,A1 .Location in patent: Paragraph 0318; 0319; 0320

68
[ 98-01-1 ]
[ 52328-05-9 ]
[ 141-97-9 ]
ethyl 4-(2-furyl)-2-methoxy-6-methyl-1,4-dihydropyrimidine-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	In N,N-dimethyl-formamide; at 70℃; for 3h;Inert atmosphere; Alkaline conditions;	Furfural (9.6 g, 0.1 mol), O-methylisothiourea sulfate (20.64 g, 0.12 mol) and ethyl acetoacetate (14.3 g, 0.11mol) were dissolved in anhydrous N,N-dimethylformamide (200 mL), sodium dicarbonate (33.6 g, 0.4 mmol) was addedthereto. The reaction mixture was heated to 70C under nitrogen atmosphere, stirred for 3 hours and cooled down toroom temperature. After addition of saturated brine (300 mL), a large amount of yellow suspended solids appeared,EtOAc (500 mL 32) was used for extraction, the organic phases were combined and washed by water (200 mL) andsaturated brine (100 mL), dried over anhydrous sodium sulfate, then concentrated under reduced pressure, and theresidue was purified by silica gel chromatography (PE:EtOAc=6-3:1) to give a pale yellow solid 2-f (15.0 g, yield: 57%).LC-MS (ESI): m/z =265.1[M+H]+.

Reference： [1]Patent: EP3594216,2020,A1 .Location in patent: Paragraph 0100; 0101

69
[ 29941-82-0 ]
[ 52328-05-9 ]
[ 4637-24-5 ]
8-ethoxy-2-methoxy-5,6-dihydroquinazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-ethoxycyclohex-2-en-1-one; <i>N</i>,<i>N</i>-dimethyl-formamide dimethyl acetal In N,N-dimethyl-formamide at 120℃; for 13h; Stage #2: O-methylisourea hydrogen sulfate With anhydrous Sodium acetate In N,N-dimethyl-formamide at 80℃; for 24h;	1.1.2 2): 8-ethoxy-2-methoxy-5,6-dihydroquinazoline (3a) The solution of compound 2a (21 g, 150.0 mmol) and N,N-dimethylformamide dimethylacetal (99.3 mL, 750.0 mol, 5 equiv.) in N,N-dimethylformamide (300 mL) was stirred at 120 °C for 13 hours. After the mixture was cooled to room temperature, the brown oily product obtained by vacuum concentration was enamine intermediate. The crude product can be directly used in the next reaction without further purification. LC-MS (ESI), C13H20N3O [M+H]+: m/z = 234.2.The crude product obtained in the above step, O-methylisourea sulfate (73.9 g, 300.0 mmol) and anhydrous sodium acetate (49.2 g, 600.0 mmol) were suspended in N, N-dimethylformamide (500 ml). The temperature of the mixture was raised to 80°C and the reaction was continued for 24 hours. After the mixture was cooled to room temperature, the mixture was diluted with dichloromethane (500 mL), suction filtered, and concentrated. The resulting residue was purified by flash silica gel column chromatography (petroleum ether/ethyl acetate = 1: 1) to afford light yellow solid product which was the title compound 3a (16.4 g, 79.5 mmol, 53%). 1H NMR (400 MHz, chloroform-d, ppm) δ 8.20 (s, 1H), 5.46 (t, J = 4.7 Hz, 1H), 3.99 (s, 3H), 3.92 (q, J = 7.0 Hz, 2H), 2.70 (t, J = 7.9 Hz, 2H), 2.40 (td, J= 7.9, 4.8 Hz, 2H), 1.44 (t, J= 7.0 Hz, 3H).

Reference： [1]Current Patent Assignee: CHENGDU SYNOWEST BIOTECHNOLOGY; CHENGDU SING BIOMEDICAL SCIENCE AND TECH; CHENGDU CYNOGEN BIO PHARMACEUTICAL TECH - EP3992196, 2022, A1 Location in patent: Paragraph 0129; 0131-0132

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P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
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.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
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

[ CAS No. 52328-05-9 ] {[proInfo.proName]}

Quality Control of [ 52328-05-9 ]

Related Doc. of [ 52328-05-9 ]

Product Details of [ 52328-05-9 ]

Calculated chemistry of [ 52328-05-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 52328-05-9 ]

Application In Synthesis of [ 52328-05-9 ]

[ 52328-05-9 ] Synthesis Path-Upstream 1~5

[ 52328-05-9 ] Synthesis Path-Downstream 1~69

Related Functional Groups of [ 52328-05-9 ]

Aliphatic Chain Hydrocarbons

Amines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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[ 52328-05-9 ]