6-Chloro-2-methyl-3-nitropyridine | 6-Chloro-3-nitro-2-picoline | Pyridines

Structure of 22280-60-0

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

Synonyms: 6-Chloro-3-nitro-2-picoline

4.5 *For Research Use Only !

{[proInfo.pro_purity]}

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

Change View

Size

Price

VIP Price

DE Stock

US Stock

Asia 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) ]}

{[ item.pr_size ]}

In Stock

- +

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

Quality Control of [ 22280-60-0 ] Purity: 98% 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 Details of [ 22280-60-0 ]

CAS No. :	22280-60-0
Formula :	C₆H₅ClN₂O₂
M.W :	172.57
SMILES Code :	C1=CC(=NC(=C1[N+](=O)[O-])C)Cl
Synonyms :	6-Chloro-3-nitro-2-picoline
MDL No. :	MFCD00234160
InChI Key :	GHSRMSJVYMITDX-UHFFFAOYSA-N
Pubchem ID :	253123

Safety of [ 22280-60-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 22280-60-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.17
Num. rotatable bonds	1
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	43.04
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	58.71 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.43
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	2.04
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.95
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.	0.22
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	0.3
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.19

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.53
Solubility	0.506 mg/ml ; 0.00293 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.9
Solubility	0.217 mg/ml ; 0.00126 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	-2.4
Solubility	0.679 mg/ml ; 0.00394 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	Yes
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	Yes
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.	-5.9 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.	0.55

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	3.0 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)	2.02

Application In Synthesis of [ 22280-60-0 ]

* 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 [ 22280-60-0 ]

[ 22280-60-0 ] Synthesis Path-Downstream 1~54

1
[ 64-18-6 ]
[ 22280-60-0 ]
[ 28489-45-4 ]

References: [1]Journal of the American Chemical Society,1954,vol. 76,p. 596,598.

2
[ 22280-60-0 ]
[ 100-67-4 ]
2-methyl-6-phenoxypyridin-3-amine [ No CAS ]

References: [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1952,vol. 72,p. 434.
Chem.Abstr.,1953,p. 6404.

3
[ 22280-60-0 ]
[ 1124-31-8 ]
2-methyl-3-nitro-6-(4-nitro-phenoxy)-pyridine [ No CAS ]

References: [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1952,vol. 72,p. 434.
Chem.Abstr.,1953,p. 6404.

4
[ 22280-60-0 ]
[ 124-41-4 ]
[ 5467-69-6 ]

References: [1]Journal of the American Chemical Society,1952,vol. 74,p. 3828,3830.

5
[ 22280-60-0 ]
[ 1193-00-6 ]
[ 28232-37-3 ]

References: [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1952,vol. 72,p. 434.
Chem.Abstr.,1953,p. 6404.

6
[ 22280-60-0 ]
[ 3784-03-0 ]
2-methyl-3-nitro-6-(2,4,6-trichloro-phenoxy)-pyridine [ No CAS ]

References: [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1952,vol. 72,p. 434.
Chem.Abstr.,1953,p. 6404.

7
[ 22280-60-0 ]
[ 111-42-2 ]
[ 104396-19-2 ]

References: [1]Journal of the Chemical Society,1957,p. 1544,1546.

8
[ 22280-60-0 ]
[ 3430-10-2 ]

References: [1]Journal of Fluorine Chemistry,2011,vol. 132,p. 541 - 547.
[2]Journal of the American Chemical Society,1939,vol. 61,p. 2562.
[3]Journal of the Chemical Society,1953,p. 1313.
[4]Journal of the American Chemical Society,1954,vol. 76,p. 596,598.

9
[ 22280-60-0 ]
[ 164666-68-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With hydrogenchloride; iron; In ethanol; water; at 20℃; for 1h;	Step 1: 6-Chloro-2-methylpyridin-3-amine (44). To a stirred solution of 43 (5 g, 29 mmol) in EtOH (20 mL) and cone. HCI (20 mL) was added Fe powder (16.2 g, 289 mmole) in small portions at RT over 30 min. Stirring was continued at RT for another 30 min. The solvent was distilled off under reduced pressure. Water was added and the resulting mixture was neutralized with NaHC03. EtOAc was added and the biphasic mixture was filtered through Celite and washed with EtOAc. The phases of the filtrate were separated and the organic layer was washed with water, brine, dried over Na2S04, and concentrated to afford 44 (4.1 g, 99 percent) as a yellow solid.
99%	With hydrogenchloride; iron; In ethanol; water; at 20℃; for 1h;	To a stirred solution of 55 (5 g, 29 mmol) in EtOH (20 mL) and cone HC1 (20 mL) was added Fe powder (16.2 g, 289 mmole) in small portions at RT over 30 min. The resulting reaction mixture was stirred at RT for an additional 30 min. The solvent was removed in vacuo and water was added to the residue which was then neutralized with NaHC03 and diluted with EtOAc. The reaction mixture was filtered through Celite and washed with EtOAc. The filtrate was transferred to a separatory funnel and the phases separated. The organic layer was washed with water and brine, dried over Na2S0 and concentrated to afford 56 (4.1 g, 99 percent) as a yellow solid.
	With 5%-palladium/activated carbon; hydrogen; In ethanol; at 40 - 45℃; under 2250.23 - 3750.38 Torr;Autoclave;	To the 1-liter autoclave was added 300 ml of ethanol, 86.3 g (0.5 mol) of <strong>[22280-60-0]6-chloro-3-nitro-2-methylpyridine</strong>, 8.6 g of a 5percent palladium-carbon catalyst, stirred and heated to 40 ~ 45 , through the high purity hydrogen, maintain the hydrogen pressure 0.3 ~ 0.5MPa, the reaction 6 ~ 8 hours, the sample sampling sample 6-chloro-3-amino-2-methyl pyridine content of less than 0.3percent The reaction was carried out at room temperature and the catalyst was filtered off and the resulting filtrate was evaporated to dryness under reduced pressure to give a gray solid which was recrystallized from a mixed solution of ethyl acetate and cyclohexane to give 56.1 g of product and a relative liquid content of 98percent , Which can be used directly for the further reaction of Example 2 below.

With iron; ammonium chloride; In methanol; at 80℃; for 5h;

A mixture of 6-chioro-2-methyi-3-nitropyridine(8.6() g, 50.00 mrnol), NH4Ci (27.00 g, 500.0() mrnol) and Fe (14.0() g, 250.00 mrnoi) in MeOK(100 mL) was stirred at 80 °C for 5 11 The mixture was filtered and concentrated, and theresulting residue was purified by column chromatography (Si02. eluting with PE:EA 5:1) toafford the title compound.

References: [1]Patent: WO2017/4608,2017,A1 .Location in patent: Paragraph 0164.
[2]Patent: WO2017/4609,2017,A1 .Location in patent: Paragraph 0235.
[3]Archiv der Pharmazie,1995,vol. 328,p. 247 - 255.
[4]Chemistry of Heterocyclic Compounds,1996,vol. 32,p. 1173 - 1177.
[5]Journal of the American Chemical Society,1947,vol. 69,p. 63,66.
[6]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 2797 - 2802.
[7]Patent: CN104003934,2016,B .Location in patent: Paragraph 0026-0027.
[8]Patent: WO2017/205193,2017,A1 .Location in patent: Page/Page column 150.

10
[ 22280-60-0 ]
[ 18699-87-1 ]

References: [1]Journal of the American Chemical Society,1954,vol. 76,p. 596,598.

11
[ 22280-60-0 ]
[ 28489-37-4 ]

References: [1]Journal of the American Chemical Society,1952,vol. 74,p. 3828,3830.

12
[ 28489-45-4 ]
[ 22280-60-0 ]

Yield	Reaction Conditions	Operation in experiment
78%	With phosphorus pentachloride; trichlorophosphate; at 150℃; for 2h;	Example 1153-((5-Amino-6-methylpyridin-2-yl)ethynyl)-7,7-dimethyl-7,8-dihydroquinoone[00319] A mixture of 6-methyl-5-nitropyridin-2-ol (500 mg, 3.24 mmol), POCI3 (0.5 mL) and PCI5 (200 mg) is stirred at 150 °C for 2 h, cooled to r.t, poured onto ice, and extracted with DCM (3x20 mL). The combined organic phases are washed with water to reach pH 7, dried over Na2S04 and concentrated at reduced pressure. The obtained residue is dried at reduced pressure to give 6-chloro-2-methyl-3-nitropyridine (430 mg, 78percent) as light brown solid.[00320]According to General Procedure 2, 3-ethynyl-7,7-dimethyl-7,8-dihydroquinolin- 5(6/-/)-one (199 mg, 1 .00 mmol) is reacted with 6-chloro-2-methyl-3-nitropyridine (172 mg, 1.00 mmol) in the presence of PdCI2(PPh3)2 (42 mg, 0.06 mmol), P(f-Bu)3 (16 mg, 0.08 mmol), and TEA (1 .5 mL) in DMF (3 mL) at 100 °C for 3 h. The crude product is purified by column chromatography (silica gel) to give the intermediate product 7,7- dimethyl-3-((6-methyl-5-nitropyridin-2-yl)ethynyl)-7,8-dihydroquinolin-5(6/-/)-one (80 mg, 16percent) as yellow solid.[00321 ]7,7-dimethyl-3-((6-methyl-5-nitropyridin-2-yl)ethynyl)-7,8-dihydroquinolin-5(6/-/)- one (194 mg, 0.58 mmol) is dissolved in EtOAc (10 mL) and cooled down to 0 °C. A solution of SnCl2*2H2O (650 mg, 2.90 mmol) in concentrated aqueous HCI solution (1 mL) is added dropwise. The reaction mixture is stirred at r.t. for 3 h, poured onto ice, treated with 15percent aqueous NaOH solution to reach pH 9-10, and extracted with EtOAc (3x25 mL). The combined organic phases are dried over Na2SO4 and concentrated at reduced pressure. The obtained residue is purified by preparative TLC (silica gel, DCM/EtOH, 40: 1 ) to provide the title compound (34 mg, 19percent).1H NMR (De-DMSO), deltaEta, 1 .05 (s, 6H), 2.29 (s, 3H), 2.59 (s, 2H), 3.03 (s, 2H), 5.51 (br s, 2H), 6.92 (d, 1 H), 7.24 (d, 1 H), 8.15 (s, 1 H), 8.83 (s, 1 H).LC/MS (M+H)+ = 306
63.8%	With phosphorus pentachloride; trichlorophosphate; at 100℃; for 2h;	The raw material 3 (150 mg) and PCl5(210 mg) and POCl3(180 mg) was placed in a round bottom flask and refluxed at 100 ° C for 2 h. The POCl was distilled off under reduced pressure3After stirring with water, the solid was precipitated and filtered under reduced pressure to give the crude product. Column chromatography gave pure product 4 (100 mg) in 63.8percent yield.
62%	With phosphorus pentachloride; trichlorophosphate; In DMF (N,N-dimethyl-formamide); at 110 - 115℃; for 8h;	(c) To 6-Hydroxy-3-nitro-2-picoline (15.73 g, 0.102 mol) was added PCls (5.73 g, 0.027 mol) and POCh (2.9 ml, 0.032 mol). This mixture was heated at 110-115°C for 3 hrs. However, the amount of POCh added was only enough to moisten the starting material. More POC13 (3 ml) was added, the reaction mixture heated at 110-115°C but only sublination of PCls (100°C) was observed. DMF (5 ml) was added and the solution was heated at 115°C for 5 hrs, cooled and poured into a slush of ice and water. A beige product precipitated and the water suspension was stirred for 48 hrs. The brown precipitate was filtered off and washed with water. Purification by dry-flash dichloromethane yielded 10.93 g (62 percent) of 6-chloro-2-picoline.

2.3 gm (85%)	With phosphorus pentachloride; trichlorophosphate;	6-chloro-3-nitro-2-picoline A mixture of 2.42 gm (15.7 mMol) 6-hydroxy-3-nitro-2-picoline, 1.0 gm phosphorus pentachloride, and 0.5 mL phosphorus oxychloride was heated at 110° C. for 2.5 hours. The reaction mixture was cooled to room temperature and then an additional 0.5 gm of phosphorus pentachloride and 0.5 mL phosphorus oxychloride were added. Heating was resumed for one hour at which point the reaction mixture poured into 100 mL of an ice/water slurry. The resultant slurry is filtered and the solid dried under vacuum to provide 2.3 gm (85percent) of the desired compound as a brown solid.
2.3 gm (85%)	With phosphorus pentachloride; trichlorophosphate;	6-chloro-3-nitro-2-picoline A mixture of 2.42 gm (15.7 mMol) 6-hydroxy-3-nitro-2-picoline, 1.0 gm phosphorus pentachloride, and 0.5 mL phosphorus oxychloride was heated at 110°C for 2.5 hours. The reaction mixture was cooled to room temperature and then an additional 0.5 gm of phosphorus pentachloride and 0.5 mL phosphorus oxychloride were added. Heating was resumed for one hour at which point the reaction mixture poured into 100 mL of an ice/water slurry. The resultant slurry is filtered and the solid dried under vacuum to provide 2.3 gm (85percent) of the desired compound as a brown solid.
		Step 2 6-Chloro-2-methyl-3 -nitropyridineA roundbottom flask was charged with a solution of 6-methyl-5-nitropyridin-2-ol (1.5 g, 9.74 mmol) in phosphorus oxychloride (5 ml). To the mixture was added phosphoryl pentachloride (2.0 g, 9.59 mmol). The resulting solution was allowed to react, with stirring, for three hours while the temperature was maintained at reflux. The mixture was poured into ice water and the solids that formed were collected by filtration to afford the title compound.

References: [1]Journal of Fluorine Chemistry,2011,vol. 132,p. 541 - 547.
[2]Patent: WO2012/52451,2012,A1 .Location in patent: Page/Page column 113.
[3]Patent: CN105906621,2016,A .Location in patent: Paragraph 0021.
[4]Patent: WO2005/42464,2005,A1 .Location in patent: Page/Page column 33.
[5]Journal of the American Chemical Society,1952,vol. 74,p. 3828,3830.
[6]Patent: US5874427,1999,A .
[7]Patent: EP875513,1998,A1 .
[8]Patent: WO2009/155156,2009,A1 .Location in patent: Page/Page column 74.

13
[ 22280-62-2 ]
[ 22280-60-0 ]
[ 28489-45-4 ]

References: [1]Journal of the American Chemical Society,1947,vol. 69,p. 63,66.

14
[ 22280-60-0 ]
[ 96592-02-8 ]
[ 96592-34-6 ]

References: [1]European Journal of Medicinal Chemistry,1984,vol. 19,p. 559 - 565.

15
[ 22280-60-0 ]
[ 77917-04-5 ]
[ 77917-45-4 ]

References: [1]Chemical and Pharmaceutical Bulletin,1981,vol. 29,p. 1594 - 1605.

16
[ 1824-81-3 ]
[ 22280-60-0 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 727 - 739.
[2]Journal of the American Chemical Society,1947,vol. 69,p. 63,66.
[3]Journal of Fluorine Chemistry,2011,vol. 132,p. 541 - 547.
[4]Patent: CN105906621,2016,A .
[5]Patent: WO2005/42464,2005,A1 .

17
[ 22280-60-0 ]
[ 25391-81-5 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 727 - 739.

18
[ 110-85-0 ]
[ 22280-60-0 ]
1-(6-methyl-5-nitro-pyridin-2-yl)-piperazine [ No CAS ]

References: [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 673 - 677.

19
[ 22280-60-0 ]
[ 152192-96-6 ]
[ 954369-02-9 ]

Yield	Reaction Conditions	Operation in experiment
70.2%	With lithium hydride; In toluene; at 90℃; for 4h;	u. r2-(5-Amino-6-methyl-pyridin-2-yloxy)-ethyll-propyl-carbamic acid ferf-butyl esteru.1 [2-(6-Methyl-5-nitro-pyridin-2-yloxy)-ethyl]-propyl-carbamic acid te/t-butyl esterA mixture of <strong>[22280-60-0]6-chloro-2-methyl-3-nitro-pyridine</strong> (1 g, 5.79 mmol), (2-hydroxy- ethyl)-propyl-carbamic acid te/t-butyl ester (1.18 g, 5.79 mmol) and lithium hydride (0.05 g, 6.37 mmol) in toluene (5 ml) was stirred at 900C for 4 h. After evaporation of the solvent under reduced pressure the residue was <n="131"/>purified by silica gel chromatography with heptane/ethyl acetate (10:0; 8:2; 0:10) as eluent to provide 1.38 g (70.2percent) of the product.MS (ESI) m/z: 284.15 [M+H(-[terf-butyl])]+

References: [1]Patent: WO2007/118859,2007,A1 .Location in patent: Page/Page column 129-130.

20
[5-isopropyl-3-(2-trifluoromethoxy-phenyl)-3H-[1,2,3]triazol-4-yl]-methanol [ No CAS ]
[ 22280-60-0 ]
[ 959801-02-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With caesium carbonate;racemic-2-(di-tert-butylphosphino)-1,1?-binaphthyl; palladium diacetate; at 70℃;	Step A; To an ambient temperature solution of [5-isopropyl-3-(2-trifluoromethoxy- phenyl)-3H-[l,2,3]triazol-4-yl]-methanol (2.0 g, 6.64 mmol) in degassed toluene (22 mL) are added <strong>[22280-60-0]6-chloro-2-methyl-3-nitro-pyridine</strong> (1.15 g, 6.64 mmol), cesium carbonate (3.25 g, 9.96 mmol), 2-(di-t-butylphosphino)-l,l '-binapthyl (332 mg, 0.833 mmol, 12.5 molpercent), and palladium (II) acetate (150 mg, 0.666 mmol, 10 molpercent). The reaction mixture is heated to 70 0C overnight. The reaction is filtered through a pad of diatomaceous earth. The filtrate is concentrated and the residue is chromatographed (SiO2 120 g, 0percent to 20percent EtOAc/Hexane to yield 6-[5-Isopropyl-3-(2-trifluoromethoxy-phenyl)-3H- [l,2,3]triazol-4-ylmethoxy]-2-methyl-3-nitro-pyridine (2.78 g, 96percent). 1H NMR (400 MHz, CDCl3) delta 8.23 (d, IH, J=8.8 Hz), 7.61-7.53 (m, 2H), 7.48-7.42 (m, 2H), 6.51 (d, IH, J=8.8 Hz), 5.42 (s, 2H), 3.26 (sept, IH, J=7.0 Hz), 2.71 (s, 3H), 1.43 (d, 6H, J=7.0 Hz).

References: [1]Patent: WO2007/140174,2007,A2 .Location in patent: Page/Page column 64.

21
[ 22280-60-0 ]
[ 959631-55-1 ]
[ 959631-51-7 ]

Yield	Reaction Conditions	Operation in experiment
94%	With caesium carbonate;palladium diacetate; johnphos; In toluene; at 20 - 70℃;	Preparation 206-r4-Isopropyl-2-(2-trifluoromethoxy-phenyl)-2H-pyrazol-3-ylmethoxy1-2-methyl-3- nitro-pyridineTo an ambient temperature solution of [4-Isopropyl-2-(2-trifluoromethoxy- phenyl)-2H-pyrazol-3-yl] -methanol (2.0 g, 6.66 mmol) in degassed toluene (22 mL) is added 6-Chloro-2-methyl-3-nitro-pyridine (1.15 g, 6.66 mmol), cesium carbonate (3.25 g, 9.99 mmol), 2-(Di-t-butylphosphino)-l,l'-binapthyl (332 mg, 0.833 mmol, 12.5 molpercent), and palladium (II) acetate (150 mg, 0.666 mmol, 10 molpercent). The reaction mixture is heated to 70 0C overnight. The reaction mixture is filtered through a pad of Celite.(R)., is concentrated under reduced pressure, and is chromatographed (0percent to 20percent EtO Ac/Hex) to yield the title compound (2.73 g, 94percent). 1H NMR (400 MHz, CDCl3) delta 8.22 (d, IH, J=8.8 Hz), 7.64 (s, IH), 7.52 (dd, IH, J=7.8, 1.7 Hz), 7.49-7.44 (m, IH), 7.41-7.34 (m, 2H), 6.51 (d, IH, J=9.2 Hz), 5.35 (s, 2H), 3.05 (sept, IH, J=7.0 Hz),2.72 (s, 3H), 1.29 (d, 6H, J=7.0 Hz).

References: [1]Patent: WO2007/140183,2007,A1 .Location in patent: Page/Page column 28.

22
[ 67-56-1 ]
[ 22280-60-0 ]
[ 5467-69-6 ]

Yield	Reaction Conditions	Operation in experiment
97%		Sodium metal (0.119g, 5.1mmol) was dissolved in methanol (6ml) at 0°C (ice bath), <strong>[22280-60-0]6-chloro-2-methyl-3-nitro-pyridine</strong> (0.30g, 1.7mmol) was added and the mixture was stirred at 0°C until the complete consumption of <strong>[22280-60-0]6-chloro-2-methyl-3-nitro-pyridine</strong> (4h). Acetic acid (0.306g, 5.1mmol) was added and the solution was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (20 ml), washed with water (10 ml), dried over anhydrous Na2SO4, filtered and the solvent was removed under reduced pressure to give 0.28g (97percent) 6-methoxy-2-methyl-3-nitropyridine as colourless powder.

References: [1]Patent: EP1894924,2008,A1 .Location in patent: Page/Page column 23.

23
[ 22280-60-0 ]
7-{4-[4-(6-methyl-5-nitro-2-pyridinyl)-1-piperazinyl]butoxy}-3,4-dihydro-2(1H)-quinolinone [ No CAS ]

References: [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 673 - 677.

24
[ 22280-60-0 ]
[ 329947-26-4 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 727 - 739.

25
[ 22280-60-0 ]
[ 329945-01-9 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 727 - 739.

26
[ 22280-60-0 ]
2-[4-chloro-2-(3-cyano-5-methyl-benzoyl)-phenoxy]-<i>N</i>-(2-methyl-6-sulfamoyl-pyridin-3-yl)-acetamide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 727 - 739.

27
[ 22280-60-0 ]
2-[4-chloro-2-(3-chloro-5-cyano-benzoyl)-phenoxy]-<i>N</i>-(2-methyl-6-sulfamoyl-pyridin-3-yl)-acetamide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 727 - 739.

28
[ 22280-60-0 ]
[ 218770-02-6 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 2797 - 2802.

29
[ 22280-60-0 ]
acetic acid 6-chloro-2-methyl-pyridin-3-yl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 2797 - 2802.

30
[ 22280-60-0 ]
[ 132606-40-7 ]