442903-28-8|Methyl 2,4-dichloronicotinate| Ambeed

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 [ 442903-28-8 ] Purity: 97% 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 [ 442903-28-8 ]

CAS No. :	442903-28-8
Formula :	C₇H₅Cl₂NO₂
M.W :	206.03
SMILES Code :	ClC1=C(C(=O)OC)C(=CC=N1)Cl
MDL No. :	MFCD11100222
InChI Key :	IBZIEMCFERTPNR-UHFFFAOYSA-N
Pubchem ID :	27282740

Safety of [ 442903-28-8 ]

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

Computational Chemistry of [ 442903-28-8 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	6
Fraction Csp3	0.14
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	45.54
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	39.19 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.94
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	2.29
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.17
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.	1.51
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	2.49
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.08

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.8
Solubility	0.328 mg/ml ; 0.00159 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.	-2.75
Solubility	0.366 mg/ml ; 0.00178 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	-3.34
Solubility	0.0944 mg/ml ; 0.000458 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.	-5.93 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	1.0 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)	1.63

Application In Synthesis of [ 442903-28-8 ]

* 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 [ 442903-28-8 ]

[ 442903-28-8 ] Synthesis Path-Downstream 1~41

1
[ 262423-77-8 ]
[ 442903-28-8 ]

Yield	Reaction Conditions	Operation in experiment
99%		Preparation of Methyl 2,4-dichloronicotinate Nitrosomethyl urea (8 g, 78.16 mmol), taken in diethyl ether (30 ml) was cooled to 0 C. and 25% aqueous KOH solution was added slowly under cooling. The ether layer was collected, dried over KOH and added dropwise to a stirring solution of 2,4-Dichloronicotinic acid (3 g, 15.62 mmol) in methanol (5 mL) at 0 C. The reaction mixture was allowed to come to room temperature within 1 hour. The organic solvent was removed under reduced pressure and the crude residue was purified by column chromatography (5-10% EtOAc in hexane) to obtain the pure methyl 2,4-dichloronicotinate (3.00 g, 99%) as colorless oil. 1H NMR (400 MHz, CDCl3): delta 8.34 (d, J=5.3 Hz, 1H), 7.33 (d, J=5.4 Hz, 1H), 3.99 (s, 3H).

References: [1]Patent: US2008/85887,2008,A1 .Location in patent: Page/Page column 17-18.

2
[ 442903-28-8 ]
[ 1018678-36-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	With sodium azide; In N,N-dimethyl-formamide; at 50℃;	Preparation of Methyl 4-azido-2-chloronicotinate Methyl 2,4-dichloronicotinate (20 g, 96.67 mmol) afforded methyl 4-azido-2-chloronicotinate (15 g, 73%) as cream colored solid following the literature procedure, J. Prakt.Chem, 2000; 342, 33-39 (reaction of Methyl 2,4-dichloronicotinate with NaN3 in DMF at 50 C. followed by aqueous workup).

References: [1]Patent: US2008/85887,2008,A1 .Location in patent: Page/Page column 18.

3
[ 442903-28-8 ]
[ 118486-94-5 ]
[ 1265175-34-5 ]
[ 1265175-50-5 ]

Yield	Reaction Conditions	Operation in experiment
35%; 18%	With bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 20℃; for 18.0h;Inert atmosphere;	To a solution of 1 (1.00 mmol) in DMF (3 mL) was added (PPh3)2PdCl2 (21 mg, 0.030 mmol) under an N2 atm and the reaction mixture was stirred for 5 min, before 2-furyl(tributyl)tin (0.32 mL, 1.0 mmol) was added. The resulting mixture was stirred for the time and at the temperature given in Table 1. H2O (40 mL) was added and the aqueous mixture extracted with EtOAc (2 × 30 mL). The combined organic phases were washed with brine (30 mL), dried (MgSO4) and evaporated in vacuo. The 1H NMR spectrum of the crude reaction mixture was recorded. The residue was dissolved in THF (8 mL), KF (ca. 200 mg) was added and the resulting suspension was stirred at ambient temperature for 18-20 h, evaporated with a small amount of silica gel and purified by flash chromatography on silica gel.

References: [1]Tetrahedron Letters,2011,vol. 52,p. 523 - 525.

4
[ 262423-77-8 ]
[ 74-88-4 ]
[ 442903-28-8 ]

Yield	Reaction Conditions	Operation in experiment
49%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 0 - 20℃;	To a solution of 2,4-dichloronicotinic acid (500 mg, 2.60 mmol) in acetonitrile (10 mL) cooled to 0 C was added DBU (0.981 mL, 6.51 mmol) followed by methyl iodide (0.814 mL, 13.0 mmol). The reaction mixture was stirred at RT overnight (14 h). After the reaction completion, the solvent was removed under reduced pressure. The residue was taken up in ethyl acetate (10 mL) and washed with water (1x5 mL), dried over Na2S04, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc-hexane) to afford methyl 2,4-dichloronicotinate (260 mg, 1.262 mmol, 49% yield) as pale yellow oil. LC/MS, (ESI) m/z 206.1 [(M+H)+, calcd for C7H6C12N02 205.97]; LC/MS retention time (method D): tR = 0.85 min. 1H NMR (300 MHz, CD3OD) delta ppm 8.42 (d, J= 5.4 Hz, 1H), 7.59 (d, J= 5.4 Hz, 1H), 3.99 (s, 3H).
49%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 0 - 20℃; for 14.0h;	To a solution of 2,4-dichloronicotinic acid (500 mg, 2.60 mmol) in acetonitrile (10 mL) cooled to 0 C was added DBU (0.981 mL, 6.51 mmol) followed by methyl iodide (0.814 mL, 13.0 mmol). The reaction mixture was stirred at RT overnight (14 h). After the reaction completion, the solvent was removed under reduced pressure. The residue was taken up in ethyl acetate (10 mL) and washed with water (1x5 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (EtOAc-hexane) to afford methyl 2,4-dichloronicotinate (260 mg, 1.262 mmol, 49% yield) as pale yellow oil.
	With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; for 2.0h;	To a solution of Example 61a (21 g, 0.11 mol) in 100 mL DMF was added CH3I (28.4 g, 0.2 mol) and potassium carbonate (34.0 g, 0.25 mol) under N2, the mixture was stirred at 50 C for 2 hrs. The reaction was then quenched by adding 80 mL water, and the mixture was exacted with EA (100 mL) and H2O.The organic layer was dried over Na2S04 and concentrated to give 20.5 g polar less yellow solid (Example 61b, crude) which was used directly in the next step without further purification. LCMS [M+1]+ 206.1

References: [1]Tetrahedron Letters,2011,vol. 52,p. 523 - 525.
[2]Patent: WO2015/116060,2015,A1 .Location in patent: Page/Page column 92.
[3]Patent: JP2015/528018,2015,A .Location in patent: Paragraph 0190.
[4]Patent: WO2017/218960,2017,A1 .Location in patent: Paragraph 00607.

5
[ 442903-28-8 ]
[ 823-96-1 ]
methyl 4-chloro-2-methylnicotinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; for 8.0h;Inert atmosphere; Reflux;	To a solution of <strong>[442903-28-8]methyl 2,4-dichloronicotinate</strong> (10.0 g, 48.5 mmol) in a solvent mixture of 1 ,4-dioxane (400 mL) and water (40 mL) was added trimethylboroxine (6.79 mL, 48.5 mmol) followed by PdCl2(dppf)-CH2Cl2 adduct (1.982 g, 2.427 mmol) and cesium carbonate (31.6 g, 97 mmol). The reaction mixture was degassed with argon for 5 minutes. The reaction mixture was heated to reflux for 8 h. The reaction mixture was cooled to room temperature and filtered through diatomaceous earth (Celite ). The bed was washed with ethyl acetate and the combined filtrate was concentrated under reduced pressure to afford the crude product which was purified by silica gel column chromatography (gradient of ethyl acetate and petroleum ether) to afford methyl 4-chloro-2-methylnicotinate (5.20 g, 28 mmol, 58% yield) as a yellow liquid. LC/MS (ESI) m/e 185.7 [(M+H)+, calcd for C8H8C1N02 185.6]; LC/MS retention time (method G): tR = 1.90 min.
31%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 70℃; for 16.0h;Inert atmosphere;	A mixture of <strong>[442903-28-8]methyl 2,4-dichloronicotinate</strong> (2 g, 9.71 mmol), trimethylboroxine (1.462 g, 11.65 mmol), Cs2C03 (6.33 g, 19.42 mmol) and PdCl2(dppf) (0.710 g, 0.971 mmol) in 1,4-dioxane (30 mL) and water (2 mL) was purged with nitrogen for 5 min and heated at 70 C for 16 h. The reaction was concentrated under reduced pressure and purified by silica gel column chromatography (EtOAc-hexane mixture) to afford methyl 4-chloro-2- methylnicotinate (550 mg, 2.94 mmol, 31% yield) as a red oil. 1H NMR (300 MHz, CD3OD) delta ppm 8.44 (d, J= 5.7 Hz, 1H), 7.43 (d, J= 5.7 Hz , 1H), 3.98 (s, 3H), 2.54 (s, 3H).
31%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 70℃; for 16.0h;Inert atmosphere;	A mixture of <strong>[442903-28-8]methyl 2,4-dichloronicotinate</strong> (2 g, 9.71 mmol), trimethylboroxine (1.462 g, 11.65 mmol), Cs2CO3 (6.33 g, 19.42 mmol) and PdCl2(dppf) (0.710 g, 0.971 mmol) in 1,4-dioxane (30 mL) and water (2 mL) was purged with nitrogen for 5 min and heated at 70 C for 16 h. The reaction was concentrated under reduced pressure and purified by silica gel column chromatography (EtOAc-hexane mixture) to afford methyl 4-chloro-2-methylnicotinate (550 mg, 2.94 mmol, 31% yield) as a red oil.

References: [1]Patent: WO2015/116060,2015,A1 .Location in patent: Page/Page column 125.
[2]Patent: WO2015/116060,2015,A1 .Location in patent: Page/Page column 92-93.
[3]Patent: JP2015/528018,2015,A .Location in patent: Paragraph 0191.

6
[ 26452-80-2 ]
[ 442903-28-8 ]