1458-01-1|Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate| Ambeed

Structure of 1458-01-1

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Quality Control of [ 1458-01-1 ] Purity: 98% SDS Specification

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Product Details of [ 1458-01-1 ]

CAS No. :	1458-01-1
Formula :	C₆H₇ClN₄O₂
M.W :	202.60
SMILES Code :	COC(=O)C1=NC(=C(N=C1N)N)Cl
MDL No. :	MFCD01928388
InChI Key :	KOOBYHRLTYIPTH-UHFFFAOYSA-N
Pubchem ID :	73827

Safety of [ 1458-01-1 ]

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

Computational Chemistry of [ 1458-01-1 ] Show Less

Physicochemical Properties

Num. heavy atoms	13
Num. arom. heavy atoms	6
Fraction Csp3	0.17
Num. rotatable bonds	2
Num. H-bond acceptors	4.0
Num. H-bond donors	2.0
Molar Refractivity	47.13
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	104.12 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.04
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	0.79
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.1
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	-0.96
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	0.01
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.2

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.8
Solubility	3.19 mg/ml ; 0.0157 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.56
Solubility	0.561 mg/ml ; 0.00277 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-1.63
Solubility	4.72 mg/ml ; 0.0233 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.97 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.38

Application In Synthesis of [ 1458-01-1 ]

* 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 [ 1458-01-1 ]

[ 1458-01-1 ] Synthesis Path-Downstream 1~41

1
[ 107-15-3 ]
[ 1458-01-1 ]
[ 87663-03-4 ]

References: [1]Chemistry - A European Journal,2011,vol. 17,p. 14104 - 14110.
[2]Archiv der Pharmazie,1992,vol. 325,p. 761 - 767.
[3]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 929 - 932.

2
[ 108-00-9 ]
[ 1458-01-1 ]
[ 146940-46-7 ]

References: [1]Archiv der Pharmazie,1992,vol. 325,p. 761 - 767.
[2]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 929 - 932.

3
[ 6331-57-3 ]
[ 1458-01-1 ]
[ 146940-54-7 ]

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

4
[ 168627-33-6 ]
[ 1458-01-1 ]
[ 146940-52-5 ]

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

5
[ 45715-47-7 ]
[ 1458-01-1 ]
[ 146940-53-6 ]

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

6
[ 1458-01-1 ]
[ 80364-48-3 ]
[ 4878-36-8 ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

Yield	Reaction Conditions	Operation in experiment
		HMRS: molecularion calcd. for C5 H6 N4 O2, m/e 154.0491; measured m/e, 154.053. Peak at m/e 110 (for M-CO2) This material can be converted in good yield to the known methyl 3,5-diaminopyrazinoate (U.S. Pat. No. 3,313,813, Example 2) by standard procedures. It in turn can be chlorinated by sulfuryl chloride to give methyl-6-chloro-3,5-diaminopyrazinoate. 3,5-Diamino-2,6-dicarboxypyrazine is available from basic hydrolysis of 3,5-diamino-2,6-dicyanopyrazine by the following reaction: SPC8

8
[ 67-56-1 ]
[ 2609-46-3 ]
[ 1458-01-1 ]

References: [1]Scientia Pharmaceutica,2004,vol. 72,p. 109 - 120.

9
[ 141-43-5 ]
[ 4023-02-3 ]
[ 1458-01-1 ]
[ 2394-67-4 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 4098 - 4115.

10
[ 64-04-0 ]
[ 4023-02-3 ]
[ 1458-01-1 ]
[ 1163-46-8 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 4098 - 4115.

11
[ 111-86-4 ]
[ 4023-02-3 ]
[ 1458-01-1 ]
N-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-N'-octyl-guanidine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 4098 - 4115.

12
[ 111-26-2 ]
[ 4023-02-3 ]
[ 1458-01-1 ]
N-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-N'-hexyl-guanidine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 4098 - 4115.

13
[ 13214-66-9 ]
[ 4023-02-3 ]
[ 1458-01-1 ]
N-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-N'-(4-phenyl-butyl)-guanidine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 4098 - 4115.

14
[ 2038-57-5 ]
[ 4023-02-3 ]
[ 1458-01-1 ]
N-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-N'-(3-phenyl-propyl)-guanidine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 4098 - 4115.

15
[ 17734-21-3 ]
[ 4023-02-3 ]
[ 1458-01-1 ]
N-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-N'-(5-phenyl-pentyl)-guanidine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 4098 - 4115.

16
[ 17734-20-2 ]
[ 4023-02-3 ]
[ 1458-01-1 ]
N-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-N'-(6-phenyl-hexyl)-guanidine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 4098 - 4115.

17
[ 17734-23-5 ]
[ 4023-02-3 ]
[ 1458-01-1 ]
N-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-N'-(8-phenyl-octyl)-guanidine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 4098 - 4115.

18
[ 1458-01-1 ]
[ 147452-34-4 ]

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

19
[ 1458-01-1 ]
[ 80364-54-1 ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

20
[ 1458-01-1 ]
[ 345624-49-9 ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

21
[ 1458-01-1 ]
[ 345219-84-3 ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

22
[ 1458-01-1 ]
[ 345301-71-5 ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

23
[ 1458-01-1 ]
[ 345300-33-6 ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

24
[ 1458-01-1 ]
5-(3,5-Diamino-6-chloro-pyrazin-2-yl)-4-ethyl-3-mercapto-1-methyl-4H-[1,2,4]triazol-1-ium; hydroxide [ No CAS ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

25
[ 1458-01-1 ]
4-Allyl-5-(3,5-diamino-6-chloro-pyrazin-2-yl)-3-mercapto-1-methyl-4H-[1,2,4]triazol-1-ium; hydroxide [ No CAS ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

26
[ 1458-01-1 ]
anhydro-1,4-dimethyl-3-mercapto-5-(3,5-diamino-6-chloropyrazinyl)-1,2,4-triazolium hydroxide [ No CAS ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

27
[ 1458-01-1 ]
5-(3,5-Diamino-6-chloro-pyrazin-2-yl)-3-mercapto-1-methyl-4-phenyl-4H-[1,2,4]triazol-1-ium; hydroxide [ No CAS ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

28
[ 1458-01-1 ]
5-(3,5-Diamino-6-chloro-pyrazin-2-yl)-4-(4-fluoro-phenyl)-3-mercapto-1-methyl-4H-[1,2,4]triazol-1-ium; hydroxide [ No CAS ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

29
[ 1458-01-1 ]
[ 79998-20-2 ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

30
[ 1458-01-1 ]
[ 25658-64-4 ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

31
[ 1458-01-1 ]
[ 26865-25-8 ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

32
[ 1458-01-1 ]
[ 33249-57-9 ]

References: [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 1017 - 1023.

33
[ 1458-01-1 ]
[ 1458-19-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With formic acid; triethylamine;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 0 - 125℃; for 12h;	Preparation Example AA-1. 3,5-Diamino-pyrazine-2-carboxylic acid methyl ester To a solution of <strong>[1458-01-1]3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester</strong> (8.00g, 39.5mmol) in tetrahydrofuran (150mL) were added tetrakis(triphenylphosphine)palladium(0) (2.28g, 1.98mmol), formic acid (2.24mL, 59.3mmol) and triethylamine (16.5mL, 119mmol) at 0°C under nitrogen atmosphere, then, the solution was stirred at 125°C for 12 hours. The reaction solution was cooled to room temperature, and a solid precipitated. This solid was collected by filtration, and the title compound (10.7g, quantitatively) was obtained as a crude product of a white solid. 1H-NMR Spectrum (DMSO-d6) delta (ppm) : 3.70(3H, s), 6.95(2H, brs), 7.21 (1H, s).
100%	With formic acid; triethylamine;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 0 - 125℃; for 12h;	To a solution of <strong>[1458-01-1]3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester</strong> (8.00g, 39.5mmol) in tetrahydrofuran (150mL) were added tetrakis(triphenylphosphine)palladium(0) (2.28g, 1.98mmol), formic acid (2.24mL, 59.3mmol) and triethylamine (16.5mL, 119mmol) at 0°C under nitrogen atmosphere, then, the solution was stirred at 125°C for 12 hours. The reaction solution was cooled to room temperature, and a solid precipitated. This solid was collected by filtration, and the title compound (10.7g, quantitatively) was obtained as a crude product of a white solid. 1H-NMR Spectrum (DMSO-d6) delta(ppm) : 3.70(3H, s), 6.95(2H, brs), 7.21 (1 H, s).

References: [1]Patent: EP1782811,2007,A1 .Location in patent: Page/Page column 53.
[2]Patent: EP1669348,2006,A1 .Location in patent: Page/Page column 61.
[3]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 6760 - 6766.

34
[ 1458-01-1 ]
[ 109-81-9 ]
[ 119646-69-4 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran;	(1) A mixture of 20 g (99.0 mmol) of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (see U.S. Pat. No. 4,029,816 for an example of how to obtain this material) and 17 g (230.0 mmol) of N-methylethylenediamine was heated at reflux under an inert atmosphere for 30 hours. The rection mixture was cooled to ambient temperature and the solid was dissolved in 100 ml of tetrahydrofuran. The solution was filtered and evaporated. The residue was crystallized from 2-propanol. There was obtained 15.0 g (61.2 mmol, 61percent) of 3,5-diamino-6-chloro-N-(2-methylaminoethyl)pyrazine-2-carboxamide; mp 142.5°-143° C. Analysis calculated for; C8 H13 ClN6 O: C, 39.27; H, 5.35; N, 34.35; Found: C, 39.28; H, 5.26; N, 34.55.

References: [1]Patent: US4910202,1990,A .

35
[ 1458-01-1 ]
[ 87663-03-4 ]

Yield	Reaction Conditions	Operation in experiment
	In ethylenediamine;	(b) A mixture of 2.0 g (10.0 mmol) of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate and 13.5 g (22.6 mmol) of ethylene diamine was allowed to stand for 3 days at ambient temperature. The excess amine was evaporated and the residue was crystallized from ethanol. There was obtained 1.38 g (5.9 mmol, 59percent) of 3,5-diamino-6-chloro-N-(2-aminoethyl)pyrazine-2-carboxamide: mp 173°-174° C. Analysis calculated for C7 H11 ClN6 O: C, 36.45: N, 4.81; N, 36.44; Found: C, 36.50; N, 4.71; N, 36.22

References: [1]Patent: US4906633,1990,A .

36
[ 60145-65-5 ]
[ 1458-01-1 ]
[ 87663-11-4 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; chloroform;	EXAMPLE 4 A mixture of 1-beta-aminoethylamino-3-alpha-naphthoxypropan-2-ol (3.9 g.) and methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (1.1 g.) was heated at 90° C. for 25 hours, cooled and chromatographed on a silica column (Merck `60`, 50 g., column 140 mm.long and 32 mm.diameter) using a 9:1 v/v mixture of chloroform and methanol as eluant. The fractions containing a product with an Rf of 0.2 when examined by thin layer chromatography using the above solvent system were collected, combined and evaporated to dryness under reduced pressure. The residue was converted into a hydrogen oxalate salt by a similar procedure to that described in Example 1, and the salt was crystallized from ethanol. There was thus obtained 3,5-diamino-6-chloro-N-beta-(2-hydroxy-3-alpha-naphthoxypropylamino)ethylpyrazine-2-carboxamide hydrogen oxalate, m.p. 224°-226° C. (with decomposition)

References: [1]Patent: US4550111,1985,A .

37
[ 89694-46-2 ]
[ 1458-01-1 ]
[ 936249-15-9 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 70 - 75℃; for 2h;	Method D To a suspension of <strong>[1458-01-1]3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester</strong> (10.9 g, 53.7 mmol) in 220 ml 1,4-dioxane and water (40 ml) was added 2-chloro-5-methoxybenzene boronic acid (20 g, 107 mmol), cesium carbonate (17.5 g, 53.7 mmol) and palladium tetrakis(triphenylphosphine) (620 mg, 0.54 mmol). The reaction was heated in an oil bath at 70-75° C. for 2 hours. The reaction was then cooled and poured into 500 ml water. The resulting slurry was stirred for 10 minutes before filtering under vacuum. The beige solid collected was then slurried in 100 ml methanol, stirred for 15 minutes, then filtered, washing the filter cake with methanol and vacuum drying to afford 17.4 g of the title product. 1H-NMR (d6-DMSO): NMR (DMSO): 3.65 (s, 3H), 3.75 (s, 3H), 6.4 (br s 2H), 6.9 (d, 1H), 7.0 (dd, 1H), 7.05 (br, s, 2H), 7.4 (d, 2H). LCMS Rt=3.74 min MS m/z 309 [MH]+

References: [1]Patent: US2007/105872,2007,A1 .Location in patent: Page/Page column 27.

38
[ 1458-01-1 ]
[ 1080018-69-4 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium hydroxide; water; In methanol; at 90℃; for 1.5h;	Preparation 1 3-Chloro-pyrazine-2,6-diamine Lithium hydroxide (12.4 g, 0.30 mol) was added to a stirred suspension of <strong>[1458-01-1]3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester</strong> (20 g, 99 mmol) in methanol (300 ml) and water (120 ml) and the reaction heated at 90° C. for 1.5 hours before allowing to cool to room temperature. The reaction was concentrated in vacuo to afford a yellow slurry and this was suspended in 1,4-dioxane (350 ml) and 2M aqueous HCl solution (200 ml,) was added. The mixture was heated at 100° C. for 2 hours and then allowed to cool before removing the 1,4-dioxane in vacuo. The resulting aqueous solution was taken to pH 8 using sodium carbonate (saturated aqueous) and extracted into ethyl acetate (3*300 ml). The combined organic layers were washed with brine (300 ml), dried (Na2SO4) and concentrated in vacuo to afford a yellow solid (11.7 g, 82percent). 1H-NMR (d6-DMSO): 5.95 (br s, 2H), 6.02 (br s, 2H), 6.82 (s, 1H). MS m/z 147 [MH]+
	With lithium hydroxide; In methanol; water; at 5 - 50℃;	Step 1 A stirred suspension of <strong>[1458-01-1]3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester</strong> (110 g, 542.9 mmol) in MeOH (500 ml) at 5-10° C. (ice-bath) is treated dropwise with a suspension of lithium hydroxide (46.6 g, 1111 mmol) in water (500 ml). The reaction mixture is heated to 50° C. for 5 hours then cooled to room temperature and stirred overnight. The resulting precipitate is collected by filtration and dried in a vacuum oven to afford Lithium 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid as the lithium salt (di-hydrate); [M-Li]- 187
	In methanol; water;	Step 1A stirred suspension of <strong>[1458-01-1]3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester</strong> (110 g, 542.9 mmol) in MeOH (500 ml) at 5-10° C. (ice-bath) is treated dropwise with a suspension of lithium hydroxide (46.6 g, benzoyl}benzoyl} mmol) in water (500 ml).The reaction mixture is heated to 50° C. for 5 hours then cooled to room temperature and stirred overnight.The resulting precipitate is collected by filtration and dried in a vacuum oven to afford Lithium 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid as the lithium salt (di-hydrate); [M-Li]- 187.

	With water; lithium hydroxide; In methanol; at 20 - 50℃;	To a suspension of <strong>[1458-01-1]3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester</strong> (10.0 g, 49.35 mmol) in methanol (5 mL) was added lithium hydroxide solution (4.17 g, 98.7 mmol in 40 mL water) at room temperature. The reaction was heated to 50 °C and stirred for 2-3 h. The temperature was lowered to room temperature and the reaction stirred overnight. The resulting precipitate was collected by filtration and dried under vacuum to yield 5 (11.3 g, 97percent). Mass (m/z): 187 [M-Li].
	With lithium hydroxide; In methanol; water; at 5 - 50℃;	A stirred suspension of <strong>[1458-01-1]3,5-diamino-6-chloro-pyrazine-2-carboxylic acid methyl ester</strong> (110 g, 542.9 mmol) in MeOH (500 ml) at 5-10° C. (ice-bath) is treated dropwise with a suspension of lithium hydroxide (46.6 g, benzoyl}benzoyl} mmol) in water (500 ml). The reaction mixture is heated to 50° C. for 5 hours then cooled to room temperature and stirred overnight. The resulting precipitate is collected by filtration and dried in a vacuum oven to afford Lithium 3,5-diamino-6-chloro-pyrazine-2-carboxylic acid as the lithium salt (di-hydrate); [M-Li] 187.
	With lithium hydroxide; water; In methanol; at 5 - 50℃; for 5h;	A stirred suspension of S^-diamino-?-chloro-pyrazine^-carboxylic acid methyl ester (1 10 g, 542.9 mmol) in MeOH (500 ml.) at 5-100C (ice-bath) is treated dropwise with a suspension of lithium hydroxide (46.6 g, 11 11 mmol) in water (500 ml_). The reaction mixture is heated to 500C for 5 hours then cooled to room temperature and stirred overnight. The resulting precipitate is collected by filtration and dried in a vacuum oven to afford the title compound as the lithium salt (di-hydrate). [M-Li]" 187

References: [1]Patent: US2007/105872,2007,A1 .Location in patent: Page/Page column 25-26.
[2]Patent: US2010/130506,2010,A1 .Location in patent: Page/Page column 107.
[3]Patent: US2011/98311,2011,A1 .
[4]Patent: WO2015/3083,2015,A1 .Location in patent: Paragraph 00224.
[5]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 2458.
[6]Patent: WO2008/135557,2008,A1 .Location in patent: Page/Page column 39.

39
[ 1458-01-1 ]
[ 4878-36-8 ]

Yield	Reaction Conditions	Operation in experiment
93%		Example 310; Synthesis of 3,5-diamino-6-chloropyrazine-2-carboxylic acid[0247] To a solution of methyl 3,5-diamino-6-chloropyrazine-2-carbamate (5 g, 0.025 mols ) in 2:1 THF/MeOH (90 mL) was added IM LiOH (62 mL, 0.062 mols ). After the reaction was stirred at r.t. 72 hrs, IN HCl (62 mL, 0.062 mols ) was added. The reaction was filtered and washed with water (3 x 10 mL) to give 3,5-diamino-6- chloropyrazine-2-carboxylic acid as white solid 4.3 g (93 percent yield). LCMS (m/z): 189.1 (MH+); LC Rt = 1.05 min.
99.6 g	With water; sodium hydroxide; In methanol; for 3h;Reflux;	A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60°C. Yield: 99.6 g (107percent of theory) C5H5ClN4O2 ESI Mass spectrum: m/z = 189 [M+H]+; m/z = 187 [M-H]-
99.6 g	With water; sodium hydroxide; In methanol; for 3h;Reflux;	3,5-Diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60° C. Yield: 99.6 g (107percent of theory) C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]-

99.6 g	With water; sodium hydroxide; In methanol; for 3h;Reflux;	Intermediate A.1 3,5-diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60° C. Yield: 99.6 g (107percent of theory) C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]-
99.6 g	With water; sodium hydroxide; In methanol; for 3h;Reflux;	A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 I) and NaOH (6 mol/l in water; 240 mL; 1 .44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60°C. Yield: 99.6 g (107percent of theory). C5H5ClN4O2. ESI Mass spectrum: m/z = 189 [M+H]+; m/z = 187 [M-H]-.
	With water; sodium hydroxide; In methanol; for 3h;Reflux;	A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 I) and NaOH (6 mol/l in water; 240 mL; 1 .44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60°C. Yield: 99.6 g (107percent of theory) ESI Mass spectrum: m/z = 189 [M+H]+; m/z = 187 [M-H]"
99.6 g	With water; sodium hydroxide; In methanol; for 3h;Reflux;	A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 mL; 1.44 mol) is refluxed for 3 h.The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60° C. Yield: 99.6 g (107percent of theory) C5H5ClN4O2 .ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]-
	With water; sodium hydroxide; In methanol; for 3h;Reflux;	Intermediate 1: 3,5-Diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 L) and NaOH (6 mol/L in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to room temperature and then neutralised by addition of hydrochloric acid (6 M in water; ca. 120 mL). Water (200 mL) is added. The precipitate formed is collected by filtration while applying suction, washed with water and dried at 60° C. Yield: 99.6 g (107percent of theory). ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]-
	With sodium hydroxide; In methanol; water; for 3h;Reflux;	A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60° C. C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]-
		Intermediate A.1 3,5-diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 I) and NaOH (6 mol/l in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60°C. C5H5CIN4O2 ESI Mass spectrum: m/z = 189 [M+H]+; m/z = 187 [M-H]"
	With water; sodium hydroxide; In methanol; for 3h;Reflux;	A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60° C. C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]-
	With water; sodium hydroxide; In methanol; for 3h;Reflux;	3,5-Diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 ml; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60° C. C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]-
	With sodium hydroxide; In methanol; water; for 3h;Reflux;	3,5-Diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 ml; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60° C. C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]-
	With sodium hydroxide; In methanol; water; for 3h;Reflux;	A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (11) and NaOH (6 moIll in water; 240 mL; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 moIll in water; approx. 240 mL). Water (200 mL) is added. The precipitate formed is fil10 tered off with suction, washed with water and dried at 60°C.C5H5C1N402 ESI Mass spectrum: mlz = 189 [M+H]+; mlz = 187 EM-Hr
7.4 g	With water; sodium hydroxide; In 1,4-dioxane; at 20℃;	3,5-Diamino-6-chloropyrazine-2-carboxylic acid Methyl-3,5-diamino-6-chloropyrazine-2-carboxylate (8.5 g, 41.9 mmol) is dissolved in dioxane (200 mL), sodium hydroxide (1 M in water, 125 mL, 125 mmol) added and the mixture stirred overnight at room temperature. The reaction mixture is acidified to pH 5 with 4 M hydrochloric acid and concentrated to one third of the initial volume. The resulting solid is collected by filtration, washed with water and dried under vacuum at 50° C. Yield: 7.4 g ESI mass spectrum: [M+H]+=189
	With sodium hydroxide; In methanol; water; for 3h;Reflux;	3,5-Diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 ml; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 mL). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60° C. C5H5ClN4O2 ESI Mass spectrum: m/z=189 [M+H]+; m/z=187 [M-H]-
7.4 g	With water; sodium hydroxide; In 1,4-dioxane; at 20℃;	Intermediate 11.1.1 3,5-Diamino-6-chloropyrazine-2-carboxylic acid Methyl-3,5-diamino-6-chloropyrazine-2-carboxylate (8.5 g, 41.9 mmol) is dissolved in dioxane (200 mL), sodium hydroxide (1 M in water, 125 mL, 125 mmol) added and the mixture stirred overnight at room temperature. The reaction mixture is acidified to pH 5 with 4 M hydrochloric acid and concentrated to one third of the initial volume. The resulting solid is collected by filtration, washed with water and dried under vacuum at 50 °C. Yield: 7.4 g ESI mass spectrum: [M+H]+ = 189 Retention time HPLC: 0.23 min (Method B)
	With sodium hydroxide; In ethanol; water; for 3h;Reflux;	Intermediate A.1 3,5-Diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 I) and NaOH (6 mol/l in water; 240 ml; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 ml_). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60°C. C5H5CIN402 ESI Mass spectrum: m/z = 189 [M+H]+; m/z = 187 [M-H]"
	With sodium hydroxide; In methanol; water; for 3h;Reflux;	Intermediate A.13,5-Diamino-6-chloropyrazine-2-carboxylic acidA mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 I) and NaOH (6 mol/l in water; 240 ml; 1 .44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 ml_). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60°C.C5H5CIN402 ESI Mass spectrum: m/z = 189 [M+H]+; m/z = 187 [M-H]-
	With sodium hydroxide; In methanol; water; for 3h;Reflux;	Intermediate A.13,5-Diamino-6-chloropyrazine-2-carboxylic acidA mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 l) and NaOH (6 mol/l in water; 240 ml; 1 .44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/l in water; approx. 240 ml_). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60°C. C5H5ClN4O2 ESI Mass spectrum: m/z = 189 [M+H]+; m/z = 187 [M-H]
		Intermediate A. l : 3,5-Diamino-6-chloropyrazine-2-carboxylic acidA mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 1) and NaOH (6 mol/1 in water; 240 ml; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/1 in water; approx. 240 riiL). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60°C.C5H5CIN4O2ESI Mass spectrum: m z = 189 [M+H]+; m z = 187 [M-H]~
	With water; sodium hydroxide; In methanol; for 3h;Reflux;	Intermediate A. l : 3,5-Diamino-6-chloropyrazine-2-carboxylic acid A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (100 g; 494 mmol), methanol (1 1) and NaOH (6 mol/1 in water; 240 ml; 1.44 mol) is refluxed for 3 h. The mixture is allowed to cool to r.t. and then neutralized by addition of hydrochloric acid (6 mol/1 in water; approx. 240 riiL). Water (200 ml) is added. The precipitate formed is filtered off with suction, washed with water and dried at 60°C. C5H5CIN4O2 ESI Mass spectrum: m z = 189 [M+H]+; m z = 187 [M-H]~

References: [1]Patent: WO2008/106692,2008,A1 .Location in patent: Page/Page column 121.
[2]Patent: WO2013/64450,2013,A1 .Location in patent: Page/Page column 40.
[3]Patent: US2013/109697,2013,A1 .Location in patent: Paragraph 0301; 0302; 0303; 0304.
[4]Patent: US2013/157981,2013,A1 .Location in patent: Paragraph 0458; 0459; 0460; 0461.
[5]Patent: WO2013/92674,2013,A1 .Location in patent: Page/Page column 55; 56.
[6]Patent: WO2013/174757,2013,A1 .Location in patent: Page/Page column 22.
[7]Patent: US2013/316981,2013,A1 .Location in patent: Paragraph 0218; 0219; 0220; 0221; 0222; 0223.
[8]Patent: US2014/88097,2014,A1 .Location in patent: Paragraph 0124-0126.
[9]Patent: US2014/323447,2014,A1 .Location in patent: Paragraph 0271; 0272; 0273.
[10]Patent: WO2014/177469,2014,A1 .Location in patent: Page/Page column 35-36.
[11]Patent: US2015/11535,2015,A1 .Location in patent: Paragraph 0152-0154.
[12]Patent: US2015/18315,2015,A1 .Location in patent: Paragraph 0153-0154.
[13]Patent: US2015/18314,2015,A1 .Location in patent: Paragraph 0113 - 0115.
[14]Patent: WO2015/3958,2015,A1 .Location in patent: Page/Page column 28.
[15]Patent: US2015/45326,2015,A1 .Location in patent: Paragraph 0240-0242.
[16]Patent: US2015/18313,2015,A1 .Location in patent: Paragraph 0159 - 0161.
[17]Patent: WO2015/18754,2015,A1 .Location in patent: Page/Page column 95.
[18]Patent: WO2015/7517,2015,A1 .Location in patent: Page/Page column 30.
[19]Patent: WO2015/7516,2015,A1 .Location in patent: Page/Page column 37.
[20]Patent: WO2015/7519,2015,A1 .Location in patent: Page/Page column 29.
[21]Patent: WO2016/113169,2016,A1 .Location in patent: Page/Page column 16.
[22]Patent: WO2016/113167,2016,A1 .Location in patent: Page/Page column 19.

40
[ 1458-01-1 ]
[ 175676-65-0 ]
[ 1076245-78-7 ]

Yield	Reaction Conditions	Operation in experiment
63%	With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 75℃; for 4h;	Preparation 1Methyl 3,5-diamino-6-r2-(trifluoromethoxy)phenyllpyrazine-2-carboxylateMETHOD AMethyl 3,5-diamino-6-chloropyrazine~2-carboxylate (1.62 g, 8.0 mmol) was combined with 2-(trifluoromethyl)phenylboronic acid (3.29 g: 16.0 mmol), palladium tetrakistriphenylphosphine (0.924 g, 0.80 mmol) and cesium carbonate (2.61 g, 8.0 mmol) and suspended in a mixture of 1 ,4-dioxane (30 ml) and water (15 ml). The reaction was sealed and heated to 750C for 4 hours before cooling to room temperature. Water (150 ml) was added and the 1 ,4-dioxane removed in vacuo. The precipitate formed was collected by filtration and dried. The brown solid was triturated with dichloromethane:methanol, then purified by silica gel column chromatography eluting with 95:5 dichloromethane:methanol to afford the title compound as a yellow solid (1.66 g, 63percent yield).1HNMR (d6-DMSO): 3.7 (s, 3H), 6.59 (br s, 2H), 7.10 (br s, 2H), 7.41-7.64 (m, 4H) LCMS Rt=8.64 min MS m/z 329 [MH]+

References: [1]Patent: WO2008/135830,2008,A1 .Location in patent: Page/Page column 53.

41
[ 1458-01-1 ]
[ 794497-98-6 ]

Yield	Reaction Conditions	Operation in experiment
82%		Preparation 14 3-Chloro-pyrazine-2,6-diamineLithium hydroxide (12.4g, 0.30 mol) was added to a stirred suspension of 3,5-diamino- 6-chloro-pyrazine-2-carboxylic acid methyl ester (20 g, 99 mmol) in methanol (300 ml) and water (120 ml) and the reaction heated at 9O0C for 1.5 hours before allowing to cool to room temperature. The reaction was concentrated in vacuo to afford a yellow slurry and this was suspended in 1 ,4-dioxane (350 ml) and 2M aqueous HCI solution (200 ml,) was added. The mixture was heated at 100 0C for 2 hours and then allowed to cool before removing the 1 ,4-dioxane in vacuo. The resulting aqueous solution was taken to pH 8 using sodium carbonate (saturated aqueous) and extracted into ethyl acetate (3 x 300 ml). The combined organic layers were washed with brine (300 ml), dried (Na2SO4) and concentrated in vacuo to afford a yellow solid (11.7g, 82percent).1HNMR(d6-DMSO): 5.95(br s, 2H), 6.02(br s, 2H), 6.82(s, 1 H).

References: [1]Patent: WO2008/135830,2008,A1 .Location in patent: Page/Page column 61.

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Bouveault-Blanc Reduction • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Catalytic Hydrogenation • Chan-Lam Coupling Reaction • Complex Metal Hydride Reductions • Ester Cleavage • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Hydride Reductions • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Leuckart-Wallach Reaction • Mannich Reaction • Petasis Reaction • Preparation of Amines • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions with Organometallic Reagents • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Vilsmeier Reagent • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Ugi Reaction

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P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
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

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CAS No.: 1458-01-1

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CAS No.: 1458-01-1

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[ 1458-01-1 ] Synthesis Path-Downstream 1~41

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[ 1458-01-1 ]

Chlorides

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[ 1458-01-1 ]

Pyrazines

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{[proInfo.proName]}

CAS No.: 1458-01-1

{[proInfo.proName]}

CAS No.: 1458-01-1

Alternative Products

Product Details of [ 1458-01-1 ]

Safety of [ 1458-01-1 ]

Computational Chemistry of [ 1458-01-1 ] Show Less

Physicochemical Properties

Lipophilicity

Water Solubility

Pharmacokinetics

Druglikeness

Medicinal Chemistry

Application In Synthesis of [ 1458-01-1 ]

[ 1458-01-1 ] Synthesis Path-Downstream 1~41

Related Products

Historical Records

Technical Information

Categories

Related Functional Groups of [ 1458-01-1 ]

Chlorides

Esters

Amines

Related Parent Nucleus of [ 1458-01-1 ]

Pyrazines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Molarity Calculator

Total Compounds Calculator

Dissolution Calculator

Related Functional Groups of
[ 1458-01-1 ]

Related Parent Nucleus of
[ 1458-01-1 ]