27398-39-6|3-Chloropyrazine-2-carboxylic acid| Ambeed

Structure of 27398-39-6

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 27398-39-6 ] Purity: 95% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Citations Show More

Evaluation of Pyrazinamide and Pyrazinoic Acid Analogues for Control of Key Weeds in Multiple Crops

Gregory R. Armel ; James T. Brosnan ; Nilda R. Burgos ; Peter J. Porpiglia ; Jose J. Vargas ;

DOI: 10.1021/acsagscitech.4c00049 ACS Agric. Sci. Technol.,2024,4(5):593-602.

Abstract: Numerous similarities exist between the structure–activity relationships of pharmaceutical drugs and pesticides, creating the potential for finding new crop management tools with novel mechanisms of action. Analogues of pyrazinamide and its active metabolite pyrazinoic acid were evaluated on a variety of monocot and dicot species to assess their potential as commercial herbicides. Six analogues, applied postemergence at 3 kg ai/ha, controlled yellow nutsedge (Cyperus esculentus) ≥ the commercial standards bentazon or imazethapyr. The compound 5-fluoropyrazine-2-carboxylic acid provided between 71 and 95% control of barnyardgrass (Echinochloa crus-galli) and yellow nutsedge with only modest injury (8–25%) to soybean (Glycine max). A similar compound containing a bromine atom in the 5-position controlled yellow nutsedge greater than bentazon and affected soybean, sweet corn (Zea mays convar. saccharata var. rugosa), and rice (Oryza sativa) in a similar fashion to bentazon as well. The herbicidal sites of action targeted by these analogues of pyrazinamide and pyrazinoic acid are unknown, but it is hypothesized that they may be disrupting targets in the biosynthesis pathways of nicotinamide adenine dinucleotide (NAD) and/or ethylene.

Keywords: herbicide ; rice ; pyrazinamide ; pharmaceutical ; prodrug ; soybean ; sweet corn

Purchased from AmBeed: 23688-89-3 ; 86873-60-1 ; 54013-04-6 ; 374068-01-6 ; 40155-43-9 ; 36070-80-1 ; 40155-42-8 ; 312736-49-5 ; 356783-15-8 ; 34604-60-9 ; 27398-39-6 ; 21279-64-1 ; 38275-61-5 ; 1211533-09-3 ; 876161-05-6 ; 5326-23-8 ; 1174321-06-2 ; 5096-73-1 ; 1060814-50-7 ; 1211584-50-7

Synthesis and Characterization of 5-(2-Fluoro-4-[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2

Yuan, Gengyang ; Dhaynaut, Maeva ; Lan, Yu ; Guehl, Nicolas J. ; Huynh, Dalena ; Iyengar, Suhasini M. , et al.

DOI: 10.1021/acs.jmedchem.1c02004 PubMed ID: 35089713 JMC,2022,65(3):2593-2609.

Abstract: Metabotropic glutamate receptor 2 (mGluR2) is a therapeutic target for several neuropsychiatric disorders. An mGluR2 function in etiology could be unveiled by positron emission tomography (PET). In this regard, 5-(2-fluoro-4-[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-7-carboxamide ([11C]13, [11C]mG2N001), a potent negative allosteric modulator (NAM), was developed to support this endeavor. [11C]13 was synthesized via the O-[11C]methylation of phenol 24 with a high molar activity of 212 ± 76 GBq/μmol (n = 5) and excellent radiochemical purity (>99%). PET imaging of [11C]13 in rats demonstrated its superior brain heterogeneity and reduced accumulation with pretreatment of mGluR2 NAMs, VU6001966 (9) and MNI-137 (26), the extent of which revealed a time-dependent drug effect of the blocking agents. In a nonhuman primate, [11C]13 selectively accumulated in mGluR2-rich regions and resulted in high-contrast brain images. Therefore, [11C]13 is a potential candidate for translational PET imaging of the mGluR2 function.

Purchased from AmBeed: 16289-54-6 ; 5521-55-1 ; 22047-25-2 ; 98-80-6 ; 40155-47-3 ; 5720-05-8 ; 879-65-2 ; 98-96-4 ; 31519-62-7 ; 23688-89-3 ; 23611-75-8 ; 33332-25-1 ; 20737-42-2 ; 61442-38-4 ; 17933-03-8 ; 50681-25-9 ; 13924-99-7 ; 40155-43-9 ; 166744-78-1 ; 36070-80-1 ; 4595-61-3 ; 118853-60-4 ; 41110-28-5 ; 40155-42-8 ; 937669-80-2 ; 31462-59-6 ; 16419-60-6 ; 5424-01-1 ; 59-67-6 ; 34604-60-9 ; 27398-39-6 ; 1196151-53-7 ; 19847-12-2 ; 13965-03-2 ; 876161-05-6 ; 27825-21-4 ; 2164-61-6 ; 4604-72-2 ; 98-97-5 ; 24005-61-6 ; 5521-61-9 ; 2516-34-9 ; 2719-27-9 ; 123-90-0 ; 6761-50-8 ; 625-43-4 ; 872-64-0 ; 1309866-36-1 ; 36932-49-7 ; 1528085-68-8 ; 1195533-51-7 ; 13534-79-7

Structure activity relationship of pyrazinoic acid analogs as potential antimycobacterial agents

Hegde, Pooja V. ; Aragaw, Wassihun W. ; Cole, Malcolm S. ; Jachak, Gorakhnath ; Ragunathan, Priya ; Sharma, Sachin , et al.

DOI: 10.1016/j.bmc.2022.117046 PubMed ID: 36228522 Bioorgan. Med. Chem.,2022,74,117046.

Abstract: Tuberculosis (TB) remains a leading cause of infectious disease-related mortality and morbidity. Pyrazinamide (PZA) is a critical component of the first-line TB treatment regimen because of its sterilizing activity against non-replicating Mycobacterium tuberculosis (Mtb), but its mechanism of action has remained enigmatic. PZA is a prodrug converted by pyrazinamidase encoded by pncA within Mtb to the active moiety, pyrazinoic acid (POA) and PZA resistance is caused by loss-of-function mutations to pyrazinamidase. We have recently shown that POA induces targeted protein degradation of the enzyme PanD, a crucial component of the CoA biosynthetic pathway essential in Mtb. Based on the newly identified mechanism of action of POA, along with the crystal structure of PanD bound to POA, we designed several POA analogs using structure for interpretation to improve potency and overcome PZA resistance. We prepared and tested ring and carboxylic acid bioisosteres as well as 3, 5, 6 substitutions on the ring to study the structure activity relationships of the POA scaffold. All the analogs were evaluated for their whole cell antimycobacterial activity, and a few representative mols. were evaluated for their binding affinity, towards PanD, through isothermal titration calorimetry. We report that analogs with ring and carboxylic acid bioisosteres did not significantly enhance the antimicrobial activity, whereas the alkylamino-group substitutions at the 3 and 5 position of POA were found to be up to 5 to 10-fold more potent than POA. Further development and mechanistic anal. of these analogs may lead to a next generation POA analog for treating TB.

Keywords: Tuberculosis ; Pyrazinoic acid ; pyrazinamide

Purchased from AmBeed: 16289-54-6 ; 5521-55-1 ; 22047-25-2 ; 98-80-6 ; 40155-47-3 ; 5720-05-8 ; 879-65-2 ; 98-96-4 ; 31519-62-7 ; 23688-89-3 ; 23611-75-8 ; 33332-25-1 ; 20737-42-2 ; 61442-38-4 ; 17933-03-8 ; 50681-25-9 ; 13924-99-7 ; 40155-43-9 ; 36070-80-1 ; 4595-61-3 ; 118853-60-4 ; 41110-28-5 ; 40155-42-8 ; 937669-80-2 ; 98-98-6 ; 31462-59-6 ; 16419-60-6 ; 5424-01-1 ; 59-67-6 ; 34604-60-9 ; 27398-39-6 ; 1196151-53-7 ; 19847-12-2 ; 13965-03-2 ; 876161-05-6 ; 27825-21-4 ; 2164-61-6 ; 4604-72-2 ; 98-97-5 ; 24005-61-6 ; 103-67-3 ; 5521-61-9 ; 2516-34-9 ; 2719-27-9 ; 123-90-0 ; 6761-50-8 ; 625-43-4 ; 872-64-0 ; 36932-49-7 ; 1528085-68-8 ; 1195533-51-7 ; 13534-79-7

Product Details of [ 27398-39-6 ]

CAS No. :	27398-39-6
Formula :	C₅H₃ClN₂O₂
M.W :	158.54
SMILES Code :	ClC1=NC=CN=C1C(=O)O
MDL No. :	MFCD01318438
InChI Key :	PMRPVXLESNMKLG-UHFFFAOYSA-N
Pubchem ID :	1501900

Safety of [ 27398-39-6 ]

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

Computational Chemistry of [ 27398-39-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	1
Num. H-bond acceptors	4.0
Num. H-bond donors	1.0
Molar Refractivity	34.0
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	63.08 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.6
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	0.6
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.83
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.	-0.61
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	0.97
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.48

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.58
Solubility	4.18 mg/ml ; 0.0264 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.	-1.5
Solubility	5.03 mg/ml ; 0.0317 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very 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	3.72 mg/ml ; 0.0234 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.	-6.84 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	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.56

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)	1.74

Application In Synthesis of [ 27398-39-6 ]

* 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 [ 27398-39-6 ]

[ 27398-39-6 ] Synthesis Path-Downstream 1~35

1
[ 14508-49-7 ]
[ 124-38-9 ]
[ 27398-39-6 ]

References: [1]Synthesis,1988,p. 881 - 884.

2
[ 20737-42-2 ]
[ 27398-39-6 ]

References: [1]Heterocycles,1984,vol. 22,p. 299 - 301.

3
[ 15454-54-3 ]
[ 27398-39-6 ]
[ 122509-59-5 ]

References: [1]Chemical and Pharmaceutical Bulletin,1990,vol. 38,p. 201 - 207.

4
[ 27398-39-6 ]
[ 90361-99-2 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; N,N-dimethyl-formamide; In toluene; at 95℃; for 1h;	3-Cl-POA (1.0 g, 6.3 mmol) was dispersed in dry toluene (approx. 50 mL) with thionyl chloride (1.4 mL, 18.9 mmol, 3 equiv.) and a catalytic amount (1-2 drops) of N,N-dimethylformamide (DMF). The reaction mixture in round bottomed flask was stirred and heated in an oil bath under a condenser at 95 °C for approximately 1 h. Solvents were evaporated in vacuo and the residue was azeotroped with dry toluene (3 × 20 mL) to remove the unreacted SOCl2 to yield crude acyl chloride [43] as brown solid, which was used without further purification.
	With thionyl chloride; N,N-dimethyl-formamide; In toluene; at 95℃; for 1h;	General procedure: A total of 0.3 g of 3-Cl-POA (1.9 mmol) was dispersed in dry toluene with thionyl chloride(0.4 mL, 5.7 mmol, 3 equiv.) and 1?2 drops of N,N-dimethylformamide (DMF) as a catalyst. Thereaction mixture was stirred and heated in a round bottom flask in an oil bath under a condenser,at 95°C for 1 h. The solvent was evaporated in vacuo and the residue was azeotroped with dry toluene(3 20 mL). The acyl chloride was used for the following step, without purification. The whole amount of the 3-chloropyrazine-2-carbonyl chloride prepared in the previousstep was dissolved in dry acetone. An appropriate benzylamine (5.7 mmol, 3 equiv., with respect to the starting acid), along with triethylamine (1.9 mmol, 1 equiv.), were added to thereaction mixture and stirred at laboratory temperature overnight. The progress of the reactionwas checked by TLC in system hexane/ethyl acetate (1:1 or 2:1). The reaction mixture wasadsorbed to silica by removing the solvents in vacuo and the product was purified by flashchromatography using gradient elution with ethyl acetate in hexane. For compounds 1?3,corresponding N-benzyl-3-(benzylamino)pyrazine-2-carboxamides 1a?3a were formed simultaneouslyin a molar ratio of approximately 2:3, with an excess of 1a?3a. Rf in hexane/ethyl acetate 1:1 mobilephase: 1a?0.85, 1?0.49, 2a?0.84, 2?0.51, 3a?0.71, and 3?0.40. After flash-chromatography,compounds 2, 2a, 3, 3a, 4, 8, and 13 were recrystallized from EtOH/H2O.
	With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; for 5h;Reflux;	1.59 g (10 mmol) of <strong>[27398-39-6]3-chloropyrazine-2-carboxylic acid</strong> was dissolved in 20 mL of dichloromethane solvent, 2.54 g (20 mmol) of oxalyl chloride, 2 drops of DMF,After stirring at reflux for 5 h, the solvent and excess oxalyl chloride were evaporated under reduced pressure.Obtained a purplish red oil; it was dissolved in 20 mL of dichloromethane.Add 0.92g (5mmol)Ethyl 5-(methylaminomethyl)-1H-imidazole-4-carboxylate and1.52 g (15 mmol) of triethylamine,After stirring at room temperature until the reaction was completed, it was poured into 50 mL of saturated sodium bicarbonate solution, and extracted with dichloromethane (20 mL × 4).After filtration, the solvent was evaporated under reduced pressure to give ethyl 5-((3-chloro-N-methylpyrazine-2-carboxamido)methyl)-1H-imidazole-4-carboxylate.Ethyl 5-((3-chloro-N-methylpyrazine-2-carboxamido)methyl)-1H-imidazole-4-carboxylate was dissolved in 20 mL of acetonitrile.Add 3.26 g (10 mmol) of cesium carbonate,The mixture was stirred under reflux until the reaction was completed, and the solvent was evaporated under reduced pressure.It was dissolved in 20 mL of dichloromethane.Wash with distilled water (30 mL × 2), dry over anhydrous sodium sulfate,After filtration, the solvent was evaporated under reduced pressure.Column chromatography (EtOAc, 1percent Et3N),A white solid was obtained in a two step yield of 55percent.

References: [1]Heterocycles,1984,vol. 22,p. 299 - 301.
[2]Magnetic Resonance in Chemistry,2009,vol. 47,p. 617 - 624.
[3]Journal of Medicinal Chemistry,2011,vol. 54,p. 635 - 654.
[4]Molecules,2015,vol. 20,p. 8687 - 8711.
[5]Molecules,2017,vol. 22.
[6]Patent: CN109206428,2019,A .Location in patent: Paragraph 0031; 0034-0035.

6
[ 27398-39-6 ]
[ 128011-39-2 ]

References: [1]Chemical and Pharmaceutical Bulletin,1990,vol. 38,p. 201 - 207.

7
[ 27398-39-6 ]
[ 128011-41-6 ]

References: [1]Chemical and Pharmaceutical Bulletin,1990,vol. 38,p. 201 - 207.

8
[ 27398-39-6 ]
[ 128011-43-8 ]

References: [1]Chemical and Pharmaceutical Bulletin,1990,vol. 38,p. 201 - 207.

9
[ 367-25-9 ]
[ 27398-39-6 ]
[ 931105-81-6 ]

Yield	Reaction Conditions	Operation in experiment
53%		Example 41; 3-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenylamino)-N-(2,4-difluorophenyl)pyrazine-2-carboxamide, bis(trifluoroacetic acid) salt; A) 3-Chloro-N-(2,4-difluorophenyl)pyrazine-2-carboxamide; To a mixture of <strong>[27398-39-6]3-chloropyrazine-2-carboxylic acid</strong> (Tyger Scientific, 500 mg, 3.15 mmol) in methylene chloride (30 mL) and DMF (0.1 mL) was added oxalyl chloride (593 mg, 4.7 mmol). After stirring 30 min the reaction mixture was concentrated in vacuo. The residue was taken up in acetonitrile (12 mL) and was treated with triethylamine (920 mg, 9.1 mmol) and 2,4-difluoroaniline (430 mg, 3.3 mmol) and stirred 30 min. The reaction mixture was partitioned between ethyl acetate and brine. The organic layer was washed with brine, dried over anhydrous MgSO4, and then concentrated in vacuo. The resulting solid was recrystallized (ethyl acetate/hexanes) to give the amide (455 mg, 53percent) as a solid. MS(ESI+) m/z 270 (M+H)+.

References: [1]Patent: US2007/78140,2007,A1 .Location in patent: Page/Page column 47-48.

10
[ 77390-81-9 ]
[ 27398-39-6 ]
[ 1060687-81-1 ]

Yield	Reaction Conditions	Operation in experiment
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2h;	Example 10 (4-Oxo-3,4-dihydro-pteridin-2-ylmethyl)-carbamic acid benzyl ester10.1 {2-[(3-Chloro-pyrazine-2-carbonyl)-amino]-2-imino-ethyl}-carbamic acid benzyl ester; Under an atmosphere of nitrogen, <strong>[27398-39-6]3-chloro-2-pyrazinecarboxylic acid</strong> (76 mg), TBTU (168 mg), and diisopropylethylamine (310 mg) were added to a solution of carbamimidoylmethyl-carbamic acid benzyl ester [77390-81-9] (99 mg) in DMF (6 ml). The reaction mixture was stirred for 2 h at ambient temperature, diluted with dichloromethane and washed with water. The organic layer was dried (Na2SO4), filtered, and the solvent was evaporated. The obtained, crude title compound (220 mg) was used without further purification in the next step.

References: [1]Patent: US2008/234277,2008,A1 .Location in patent: Page/Page column 19.

11
[ 958358-70-8 ]
[ 27398-39-6 ]
[ 1060687-63-9 ]

Yield	Reaction Conditions	Operation in experiment
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 4.5h;	2.3 3-Chloro-pyrazine-2-carboxylic acid{2-[2-(2,5-difluoro-phenyl)-ethoxy]-1-imino-ethyl}-amide; 2-[2-(2,5-Difluoro-phenyl)-ethoxy]-acetamidine hydrochloride (158 mg, 0.631 mmol) was dissolved in DMF (3 ml) and <strong>[27398-39-6]3-chloro-2-pyrazine-carboxylic acid</strong> (100 mg, 0.631 mmol), TBTU (213 mg, 0.662 mmol) and DIPEA (565 mul, 3.15 mmol) were added. The reaction mixture was stirred at ambient temperature for 4.5 h. Then water was added and the mixture was extracted three times with CH2Cl2. The combined organic extracts were washed with water and brine, dried (Na2SO4) and evaporated. The crude title compound (195 mg, brown gum) was used for the next reaction step without further purification. MS: m/e=355.2 [M+H+].

References: [1]Patent: US2008/234277,2008,A1 .Location in patent: Page/Page column 16.

12
[ 958361-36-9 ]
[ 27398-39-6 ]
[ 1060687-79-7 ]

Yield	Reaction Conditions	Operation in experiment
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2h;	9.3 3-Chloro-pyrazine-2-carboxylic acid[1-imino-2-(2-naphthalen-2-yl-ethoxy)-ethyl]-amide; Under an atmosphere of nitrogen, <strong>[27398-39-6]3-chloro-2-pyrazinecarboxylic acid</strong> (Tyger, 250 mg), TBTU (532 mg), and diisopropylethylamine (1.34 ml) were added to a solution of 2-(2-naphthalen-2-yl-ethoxy)-acetamidine hydrochloride (417 mg) in DMF (5 ml). The reaction mixture was stirred for 2 h at r.t., diluted with dichloromethane and washed with water. The organic layer was dried (Na2SO4), filtered, and the solvent was evaporated. The obtained, crude title compound (567 mg) was used without further purification in the next step.

References: [1]Patent: US2008/234277,2008,A1 .Location in patent: Page/Page column 19.

13
[ 951017-47-3 ]
[ 27398-39-6 ]
[ 951017-43-9 ]

Yield	Reaction Conditions	Operation in experiment
69%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In chloroform; at 20℃; for 12h;	3-4) To a solution of <strong>[27398-39-6]2-chloropyrazine-3-carboxylic acid</strong> (0.15 g, 1.0 mmol), 1-[1-(2,4-dichlorophenyl)cyclopropyl]ethylamine hydrochloride (0.25 g, 0.94 mmol) and 4-dimethylaminopyridine (0.29 g, 2.4 mmol) in chloroform (10 ml) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.22 g, 1.2 mmol) and the mixture was stirred at room temperature for 12 hrs. After adding water and chloroform, the mixture was separated, and the organic layer was washed successively with water and saturated brine and dried over anhydrous sodium sulfate. The mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1) to give a desired compound (yield; 0.24 g, 69percent). property; 1H-NMR [CDCl3/TMS,delta value (ppm)]: 8.53(d, 1H), 8.47(d, 1H), 7.55(br, 1H), 7.37(d, 1H), 7.32(d, 1H), 7.19(dd, 1H), 4.11(m, 1H), 1.28(m, 1H),1.23(d, 3H), 1.01(m, 1H), 0.90(m, 2H)

References: [1]Patent: EP1997800,2008,A1 .Location in patent: Page/Page column 48.

14
[ 1007571-93-8 ]
[ 27398-39-6 ]
C₂₄H₁₇BrCl₂FN₃O₄ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 7449 - 7458.

15
3-chloropyrazine-2-carboxylic acid ethyl ester [ No CAS ]
[ 27398-39-6 ]

References: [1]Magnetic Resonance in Chemistry,2009,vol. 47,p. 617 - 624.

16
[ 20737-42-2 ]
[ 27398-39-6 ]

References: [1]Magnetic Resonance in Chemistry,2009,vol. 47,p. 617 - 624.

17
[ 27825-21-4 ]
[ 27398-39-6 ]

References: [1]Magnetic Resonance in Chemistry,2009,vol. 47,p. 617 - 624.

18
[ 27398-39-6 ]
3-chloropyrazine-2-carboxylic acid ethyl ester [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 635 - 654.

19
[ 27398-39-6 ]
[ 1186038-36-7 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 635 - 654.

20
[ 27398-39-6 ]
C₁₉H₁₃ClN₄O₂ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 635 - 654.

21
[ 27398-39-6 ]
[ 1262235-73-3 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 635 - 654.

22
[ 27398-39-6 ]
[ 1262235-76-6 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 635 - 654.

23
[ 6638-79-5 ]
[ 27398-39-6 ]
[ 1223444-94-7 ]