Home Cart 0 Sign in  
X

[ CAS No. 42521-09-5 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 42521-09-5
Chemical Structure| 42521-09-5
Chemical Structure| 42521-09-5
Structure of 42521-09-5 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 42521-09-5 ]

Related Doc. of [ 42521-09-5 ]

Alternatived Products of [ 42521-09-5 ]

Product Details of [ 42521-09-5 ]

CAS No. :42521-09-5 MDL No. :MFCD00044409
Formula : C7H5Cl2NO2 Boiling Point : -
Linear Structure Formula :- InChI Key :XSKGHSUHOYEBTK-UHFFFAOYSA-N
M.W : 206.03 Pubchem ID :93237
Synonyms :

Calculated chemistry of [ 42521-09-5 ]

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 : 39.19 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.69 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.13
Log Po/w (XLOGP3) : 2.63
Log Po/w (WLOGP) : 2.17
Log Po/w (MLOGP) : 1.51
Log Po/w (SILICOS-IT) : 2.49
Consensus Log Po/w : 2.19

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.01
Solubility : 0.2 mg/ml ; 0.000972 mol/l
Class : Soluble
Log S (Ali) : -3.1
Solubility : 0.162 mg/ml ; 0.000788 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.34
Solubility : 0.0944 mg/ml ; 0.000458 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.68

Safety of [ 42521-09-5 ]

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

Application In Synthesis of [ 42521-09-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 42521-09-5 ]
  • Downstream synthetic route of [ 42521-09-5 ]

[ 42521-09-5 ] Synthesis Path-Upstream   1~19

  • 1
  • [ 42521-09-5 ]
  • [ 42521-08-4 ]
Reference: [1] Organic Letters, 2003, vol. 5, # 7, p. 967 - 970
[2] Organic Letters, 2001, vol. 3, # 26, p. 4263 - 4265
[3] Arkivoc, 2011, vol. 2011, # 6, p. 92 - 119
[4] ChemMedChem, 2013, vol. 8, # 6, p. 967 - 975
  • 2
  • [ 42521-09-5 ]
  • [ 2587-02-2 ]
Reference: [1] ChemMedChem, 2013, vol. 8, # 6, p. 967 - 975
  • 3
  • [ 42521-09-5 ]
  • [ 101990-69-6 ]
Reference: [1] Tetrahedron, 2007, vol. 63, # 2, p. 291 - 298
[2] Journal of the American Chemical Society, 2005, vol. 127, # 29, p. 10124 - 10125
  • 4
  • [ 42521-09-5 ]
  • [ 105596-63-2 ]
Reference: [1] Helvetica Chimica Acta, 1955, vol. 38, p. 1046,1058
  • 5
  • [ 42521-09-5 ]
  • [ 544-97-8 ]
  • [ 142896-15-9 ]
YieldReaction ConditionsOperation in experiment
96% With palladium bis[bis(diphenylphosphino)ferrocene] dichloride In 1,4-dioxane; toluene at 80℃; for 4 h; Inert atmosphere Compound 99: 2,6-Dimethyl-isonicotinic acid methyl ester. Under inert atmosphere, a mixture of methyl 2,6-dichloropyridine-4-carboxylate (2,00 g), dimethylzinc (2N in toluene, 14.6 mL, 3.0 equiv.) and PdCl2(dppf)2 (400 mg, 0.05 equiv.) in dioxane (50 mL), was heated at 80°C for 4Hrs. The reaction mixture was cooled by an ice bath, hydrolysed with water (100 mL) and filtered through a pad of celite. The pad was rinsed with water and EtAOc. The filtrate was extracted with EtOAc (250 mL). The organic layer was washed with brine (100 mL), dried over MgSO4 and concentrated. Purification by flash-chromatography (MeOH in CH2Cl2, 0 to 2percent) afforded compound 99 as an orange oil in 96percent yield. 1H-NMR (400 MHz, DMSO): 2.51 (s, 6H, 2CH3); 3.88 (s, 3H, O-CH3); 7.51 (s, 2H, Ar). M/Z (M+H)+ = 166.1.
96% With palladium bis[bis(diphenylphosphino)ferrocene] dichloride In 1,4-dioxane; toluene at 80℃; for 4 h; Inert atmosphere Under inert atmosphere, a mixture of methyl 2,6-dichloropyridine-4-carboxylate (2,00 g), dimethylzinc (2N in toluene, 14.6 ml, 3.0 equiv.) and PdCI2(dppf)2 (400 mg, 0.05 equiv.) in dioxane (50 ml), was heated at 80°C for 4Hrs. The reaction mixture was cooled by an ice bath, hydrolysed with water (100 ml) and filtered through a pad of celite. The pad was rinsed with water and EtAOc. The filtrate was extracted with EtOAc (250 ml). The organic layer was washed with brine (1 00 ml), dried over MgSO4 and concentrated. Purification by flash chromatography (MeOH in CH2Cl2, 0 to 2percent) afforded compound 99 as an orange oil in 96percent yield. 1H-NMR (400 MHz, DMSO): 2.51 (s, 6H, 2CH3); 3.88 (s, 3H, O-CH3); 7.51 (s, 2H, Ar). M/Z(M+H)+ = 166.1.
Reference: [1] Patent: EP2666775, 2013, A1, . Location in patent: Paragraph 0390
[2] Patent: WO2013/174822, 2013, A1, . Location in patent: Page/Page column 137
  • 6
  • [ 42521-09-5 ]
  • [ 26156-51-4 ]
Reference: [1] Helvetica Chimica Acta, 1955, vol. 38, p. 1046,1058
  • 7
  • [ 42521-09-5 ]
  • [ 6274-82-4 ]
Reference: [1] Journal of the American Pharmaceutical Association (1912-1977), 1953, vol. 42, p. 457,463
[2] Yakugaku Zasshi, 1953, vol. 73, p. 845,846, 847[3] Chem.Abstr., 1954, p. 10021
  • 8
  • [ 99-11-6 ]
  • [ 75-57-0 ]
  • [ 42521-09-5 ]
Reference: [1] Organic Letters, 2003, vol. 5, # 7, p. 967 - 970
[2] Journal of the American Chemical Society, 2005, vol. 127, # 29, p. 10124 - 10125
[3] ChemMedChem, 2013, vol. 8, # 6, p. 967 - 975
[4] Organic Letters, 2008, vol. 10, # 19, p. 4383 - 4386
[5] Arkivoc, 2011, vol. 2011, # 6, p. 92 - 119
  • 9
  • [ 5398-44-7 ]
  • [ 42521-09-5 ]
YieldReaction ConditionsOperation in experiment
86.7% With sulfuric acid In methanol; dichloromethane Step I.
Preparation of methyl-2,6-dichloroisonicotinate
A solution of 187 g (0.974 mole) of 2,6-dichloroisonicotinic acid, 1650 ml of methanol and 5 ml of concentrated sulfuric acid was heated at reflux for 24 hours.
Most of the solvent was removed in vacuo, leaving crude product which was dissolved in 750 ml of methylene chloride and washed with water and 1N sodium hydroxide.
The organic layer was dried (Na2 SO4) and solvent removed in vacuo affording 174 g (86.7percent yield) of methyl 2,6-dichloroisonicotinate, m.p. 79°-81° C.
Reference: [1] Patent: US4474602, 1984, A,
  • 10
  • [ 67-56-1 ]
  • [ 5398-44-7 ]
  • [ 42521-09-5 ]
YieldReaction ConditionsOperation in experiment
21 g for 3 h; Reflux To a stirred solution of 2,6-dichloropyridine-4-carboxylic acid (CAS Number 5398-44-7, available from Ark Pharma) (20.00 g, 104.700 mmol) in methanol (400 ml) was added concentrated sulphuric acid (20 ml) at ambient temperature. The reaction mixture was refluxed for 3 h. The resulting reaction mixture was cooled to ambient temperature, concentrated under reduced pressure and poured into saturated solution of NaHCC>3 (100 ml). The resulting reaction mixture was extracted with ethyl acetate (3 x 50 ml). The combined organic phase was dried over Na2S04, filtered and concentrated under reduced pressure yielding methyl 2,6-dichloropyridine-4-carboxylate (21 .00 g, 102.450 mmol), which was used in the next step without further purification.
Reference: [1] Organic Process Research and Development, 2016, vol. 20, # 9, p. 1637 - 1646
[2] Chemical Communications, 2015, vol. 51, # 61, p. 12258 - 12261
[3] ChemMedChem, 2015, vol. 10, # 1, p. 116 - 133
[4] Tetrahedron, 2007, vol. 63, # 2, p. 291 - 298
[5] Chemistry - A European Journal, 2010, vol. 16, # 33, p. 10202 - 10213
[6] Chemistry - A European Journal, 2011, vol. 17, # 5, p. 1473 - 1484
[7] Chemical Communications, 2015, vol. 51, # 74, p. 14123 - 14126
[8] Monatshefte fuer Chemie, 1915, vol. 36, p. 734
[9] Patent: WO2005/26149, 2005, A1, . Location in patent: Page/Page column 81
[10] Patent: WO2012/41476, 2012, A1, . Location in patent: Page/Page column 187-188
[11] Patent: EP2441755, 2012, A1, . Location in patent: Paragraph 0332
[12] Patent: US2018/148457, 2018, A1, . Location in patent: Paragraph 1335; 1336
[13] Patent: WO2018/167276, 2018, A1, . Location in patent: Paragraph 00137; 00138
  • 11
  • [ 67-56-1 ]
  • [ 42521-08-4 ]
  • [ 42521-09-5 ]
Reference: [1] Journal of Organic Chemistry, 2002, vol. 67, # 23, p. 8269 - 8272
[2] Organic Letters, 2001, vol. 3, # 26, p. 4263 - 4265
[3] Patent: WO2004/46103, 2004, A2, . Location in patent: Page 33-34
  • 12
  • [ 67-56-1 ]
  • [ 99-11-6 ]
  • [ 42521-09-5 ]
Reference: [1] Dalton Transactions, 2017, vol. 46, # 12, p. 4075 - 4085
[2] Synthesis, 2008, # 17, p. 2764 - 2770
  • 13
  • [ 22652-14-8 ]
  • [ 42521-09-5 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1988, p. 227 - 234
  • 14
  • [ 99-11-6 ]
  • [ 42521-09-5 ]
Reference: [1] Tetrahedron, 2007, vol. 63, # 2, p. 291 - 298
[2] Chemical Communications, 2015, vol. 51, # 74, p. 14123 - 14126
  • 15
  • [ 99-11-6 ]
  • [ 42521-09-5 ]
Reference: [1] ChemMedChem, 2015, vol. 10, # 1, p. 116 - 133
  • 16
  • [ 67-56-1 ]
  • [ 42521-09-5 ]
  • [ 91416-06-7 ]
  • [ 6937-04-8 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1988, p. 227 - 234
  • 17
  • [ 42521-09-5 ]
  • [ 5398-44-7 ]
YieldReaction ConditionsOperation in experiment
100% With lithium hydroxide In tetrahydrofuran; water Reagents and conditions: a) n-BuLi, ArBr; ZINC12 ; then 2,6- dibromopyridine and cat. Pd (PPH3) 4 (95percent); b) LiOH, THF/H2O (100percent); C) (COCI) 2; NaN3 ; TFA; d) K2CO3, CH30H (78percent); e) HCI, CH3CN, NAN02 ; KI (52percent); f) n-BuLi, ArBr; ZINC12 ; then 13 and cat. Pd (PPh3) 4 (98percent); g) ArB (OH} 2, cat. Pd2 (dba) 3, cat. P (T-BU) 3, CS2CO3, (82percent); h) as (F) (71percent) ; i) as (g) (31percent) ; j) n-BuLi, ArBr; ZINC12 ; then 12 (80percent) ; k) 2- aminophenol, EDCI (97percent); 1) 230°C (87percent); m) ArB (OH) 2, cat. Pd2 (dba) 3, cat. [HP (T-BU) 3] BF4, CS2CO3 (78percent). Synthesis of 4 begins with pyridine derivative citrazinic acid. Treatment with POC13 at elevated temperature afforded the corresponding 2-6, dichloroisonicotinoyl chloride. To facilitate purification, the reaction was quenched with methanol; methyl ester 1 was isolated in 76percent yield after passage through a plug of silica gel to remove colored impurities. Saponification then provided acid 2 in quantitative yield without purification. Transformation to 3 was effected by conversion to the acyl azide, thermal Curtius rearrangement, and hydrolysis of the resulting trifluoroacetamide to provide 2, 6-DICHLORO-4-AMINOPYRIDINE (3), (Pfister, J. R. , Wymann, W. E. Synthesis 1983,38). While this method for converting 2 to 3 is nominally 3 steps, it requires only a single extractive workup and the steps can thus be carried out in rapid succession. 3 was converted directly to 4 by diazotization and reaction with potassium iodide (it is necessary to stir 3 in cold hydrochloric acid for several hours prior to diazotization in order to obtain an acceptable yield) providing 4 in reasonable yield and excellent purity after trituration with acetone. This short sequence of reactions allows preparation of 4 IN-35percent overall yield, requires no chromatography beyond a single filtration through a plug of silica gel, and has allowed the routine preparation of 5-10 g quantities of this intermediate. Unlike many 4-halopyridines, 4 is stable for several months at room temperature if protected from light. 4 can be ready transformation to fluorophores of the present invention.
Reference: [1] Organic Letters, 2003, vol. 5, # 7, p. 967 - 970
[2] Journal of the American Chemical Society, 2005, vol. 127, # 29, p. 10124 - 10125
[3] Organic Letters, 2001, vol. 3, # 26, p. 4263 - 4265
[4] Patent: WO2004/46103, 2004, A2, . Location in patent: Page 33-34; 39-40
[5] ChemMedChem, 2013, vol. 8, # 6, p. 967 - 975
[6] Organic Letters, 2008, vol. 10, # 19, p. 4383 - 4386
[7] Arkivoc, 2011, vol. 2011, # 6, p. 92 - 119
  • 18
  • [ 42521-09-5 ]
  • [ 2897-43-0 ]
Reference: [1] ChemMedChem, 2013, vol. 8, # 6, p. 967 - 975
  • 19
  • [ 42521-09-5 ]
  • [ 193001-91-1 ]
Reference: [1] Patent: WO2012/138590, 2012, A1,
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 42521-09-5 ]

Chlorides

Chemical Structure| 1604-14-4

[ 1604-14-4 ]

2,6-Dichloro-isonicotinic acid ethyl ester

Similarity: 0.97

Chemical Structure| 75308-46-2

[ 75308-46-2 ]

tert-Butyl 2,6-dichloroisonicotinate

Similarity: 0.93

Chemical Structure| 5398-44-7

[ 5398-44-7 ]

2,6-Dichloroisonicotinic acid

Similarity: 0.93

Chemical Structure| 137520-99-1

[ 137520-99-1 ]

Ethyl 2,6-dichloro-3-methylisonicotinate

Similarity: 0.90

Chemical Structure| 58481-11-1

[ 58481-11-1 ]

Methyl 2-chloroisonicotinate

Similarity: 0.89

Esters

Chemical Structure| 1604-14-4

[ 1604-14-4 ]

2,6-Dichloro-isonicotinic acid ethyl ester

Similarity: 0.97

Chemical Structure| 75308-46-2

[ 75308-46-2 ]

tert-Butyl 2,6-dichloroisonicotinate

Similarity: 0.93

Chemical Structure| 137520-99-1

[ 137520-99-1 ]

Ethyl 2,6-dichloro-3-methylisonicotinate

Similarity: 0.90

Chemical Structure| 58481-11-1

[ 58481-11-1 ]

Methyl 2-chloroisonicotinate

Similarity: 0.89

Chemical Structure| 65515-28-8

[ 65515-28-8 ]

Methyl 2,6-dichloronicotinate

Similarity: 0.87

Related Parent Nucleus of
[ 42521-09-5 ]

Pyridines

Chemical Structure| 1604-14-4

[ 1604-14-4 ]

2,6-Dichloro-isonicotinic acid ethyl ester

Similarity: 0.97

Chemical Structure| 75308-46-2

[ 75308-46-2 ]

tert-Butyl 2,6-dichloroisonicotinate

Similarity: 0.93

Chemical Structure| 5398-44-7

[ 5398-44-7 ]

2,6-Dichloroisonicotinic acid

Similarity: 0.93

Chemical Structure| 137520-99-1

[ 137520-99-1 ]

Ethyl 2,6-dichloro-3-methylisonicotinate

Similarity: 0.90

Chemical Structure| 58481-11-1

[ 58481-11-1 ]

Methyl 2-chloroisonicotinate

Similarity: 0.89