Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
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 : |
|
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 |
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 |
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 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
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 |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.68 |
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: |
* 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.
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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. |
[ 1604-14-4 ]
2,6-Dichloro-isonicotinic acid ethyl ester
Similarity: 0.97
[ 75308-46-2 ]
tert-Butyl 2,6-dichloroisonicotinate
Similarity: 0.93
[ 137520-99-1 ]
Ethyl 2,6-dichloro-3-methylisonicotinate
Similarity: 0.90
[ 1604-14-4 ]
2,6-Dichloro-isonicotinic acid ethyl ester
Similarity: 0.97
[ 75308-46-2 ]
tert-Butyl 2,6-dichloroisonicotinate
Similarity: 0.93
[ 137520-99-1 ]
Ethyl 2,6-dichloro-3-methylisonicotinate
Similarity: 0.90
[ 1604-14-4 ]
2,6-Dichloro-isonicotinic acid ethyl ester
Similarity: 0.97
[ 75308-46-2 ]
tert-Butyl 2,6-dichloroisonicotinate
Similarity: 0.93
[ 137520-99-1 ]
Ethyl 2,6-dichloro-3-methylisonicotinate
Similarity: 0.90