Structure of 3-Chloropyridine
CAS No.: 626-60-8
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CAS No. : | 626-60-8 |
Formula : | C5H4ClN |
M.W : | 113.55 |
SMILES Code : | ClC1=CC=CN=C1 |
MDL No. : | MFCD00006375 |
InChI Key : | PWRBCZZQRRPXAB-UHFFFAOYSA-N |
Pubchem ID : | 12287 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H227-H302-H315-H319-H335 |
Precautionary Statements: | P210-P241-P261-P264-P270-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P330-P370+P378-P362+P364-P403+P233-P501 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 29.25 |
TPSA ? Topological Polar Surface Area: Calculated from |
12.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.49 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.33 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.73 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.06 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.15 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.55 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.02 |
Solubility | 1.09 mg/ml ; 0.00963 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.2 |
Solubility | 7.13 mg/ml ; 0.0628 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.58 |
Solubility | 0.297 mg/ml ; 0.00262 mol/l |
Class? Solubility class: Log S scale |
Soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.05 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.04 |
* 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 |
---|---|---|
0.5 g | Stage #1: With lithium diisopropyl amide In tetrahydrofuran at -75℃; for 4 h; Stage #2: With iodine In tetrahydrofuran at -75℃; for 1 h; |
To a cold solution of 3-chloro pyridine (1.0 g, 8.88 mmol) in THF (30.0 mL) was added LDA (5.9 mL, 8.88 mmol) at -75°C. The reaction mixture was stirred at -75°C for 4 h. Iodine (2.2 g, 8.88 mmol) was added and continued stirring at -75°C for 1 h. The reaction mixture was quenched in water at -70°C, extracted with ethyl acetate and concentrated to afford 0.500 g of desired product. 1H NMR (300 MHz, DMSO d6): δ 8.01 (d, J = 5.1 Hz, 1H), 8.14 (d, / = 4.8 Hz, 1H), 8.63 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Intermediate C8: 3-Chloro-4-phenylpyridin-2-olStep 1 : 3-Chloro-4-iodopyridineThe title compound was prepared according to the following reference: 35 Heterocvcles 151-69 (1993). To a solution of DIPA (3.77 mL, 26.4 mmol) in THF (20 mL) under N2 in a dry ice bath, M-BuLi (10.6 mL, 26.4 mmol) was added. The mixture was stirred in an ice bath for 20 minutes, then treated dropwise over 10 minutes with a solution of 3-chloropyridine (2.51 mL, 26.4 mmol) in 5 mL THF, keeping the temperature less than -70C. The lithiopyridine partially precipitated as a colorless solid in a light orange solution. The mixture was stirred for 30 minutes in a dry ice bath, and then I2 (6.71 g, 26.4 mmol) in 15 mL THF was added, keeping the temperature less then -650C. The solution was then allowed to warm to O0C and was placed in an ice bath for 2 hours, and then poured into 10% NaHSO3 and extracted with ether (150 mL; 3x). The organics were washed with 50 mL each OfNaHSO3, NaHCO3, H2O, and brine. The residue was purified on SiO2 (gradient elution, 2-20% EtOAc/hexanes) to give the title compound (3.35 g, 85% pure). This was then recrystallized EPO <DP n="56"/>from hot hexanes plus a few mL of EtOAc to dissolve initially to give the title compound as a white powder (1.95 g). LRMS ESf (M+H)+ 240.0. | ||
(A) Synthesis of 3-chloro-4-trifluoromethylpyridine-2- carboxylic acid; <n="110"/>(1) 3-Chloro-4-iodopyridine was obtained from 3-chloropgammaridine by the method described in Tetrahedron (1993.) 49 (1), 49. | ||
0.5 g | To a cold solution of 3-chloro pyridine (1.0 g, 8.88 mmol) in THF (30.0 mL) was added LDA (5.9 mL, 8.88 mmol) at -75C. The reaction mixture was stirred at -75C for 4 h. Iodine (2.2 g, 8.88 mmol) was added and continued stirring at -75C for 1 h. The reaction mixture was quenched in water at -70C, extracted with ethyl acetate and concentrated to afford 0.500 g of desired product. 1H NMR (300 MHz, DMSO d6): delta 8.01 (d, J = 5.1 Hz, 1H), 8.14 (d, / = 4.8 Hz, 1H), 8.63 (s, 1H). |
With n-butyllithium; iodine; diisopropylamine; sodium sulfite; In tetrahydrofuran; hexane; | 1) Preparation of 3-Chloro-4-iodopyridine To 76 ml of an anhydrous THF solution of 10 ml of diisopropylamine was added 48.6 ml (1.57 M hexane solution) of n-butyllithium at -78 C., and the mixture was stirred at that temperature for 30 minutes. To the reaction mixture was added 10 ml of a THF solution of 8.66 g of 3-chloropyridine, followed by stirring at -78 C. for 30 minutes. To the reaction mixture was further added 30 ml of a THF solution of 19.4 g of iodine, followed by stirring at the same temperature for 30 minutes. The temperature was raised to 0 C., at which the mixture was stirred for 2.5 hours. The reaction mixture was poured into 300 ml of a 8% sodium sulfite aqueous solution and extracted with diethyl ether. The organic layer was washed successively with a 10% sodium hydrogencarbonate aqueous solution, water, and a saturated sodium chloride aqueous solution and dried. The solvent was evaporated, and the residue was subjected to silica gel column chromatography using a mixture of ethyl acetate and hexane (1:9 by volume) as a developing solution. The fraction containing the desired compound was concentrated to give 4.54 g of the title compound. 1H-NMR (CDCl3) delta: 7.80 (d, 1H, J=5 Hz), 8.07 (d, 1H, J=5 Hz), 8.56 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dihydrogen peroxide; nitric acid; In sulfuric acid; water; acetic anhydride; | 1. Preparation of 3-Chloro-4-nitropyridine N-oxide Aqueous hydrogen peroxide (30 mL of 30%) is added dropwise to an ice cold mixture of 3-chloropyridine (6.0 g, 53 mmol) in acetic anhydride (30 mL). The mixture is allowed to stir at ambient temperature for 24 h, water is then added and the mixture concentrated. The residue is taken up in concentrated sulfuric acid (10 mL) and fuming sulfuric acid (5 mL), and then cooled to 0 C. Concentrated nitric acid (24 mL) is added slowly, and the ice bath removed. The reaction is then heated at reflux for 2 h, icooled, and poured into ice water. Ammonium bicarbonate is added carefully until pH 8 is achieved, the solution is then extracted with dichloromethane. The organic layer is washed with water, dried (NaSO4), and concentrated to give 3-Chloro-4-nitropyridine N-oxide as a yellow solid. 1H NMR (CDCl3): delta 8.47 (d, J=4 Hz, H), 8.35 (dd, J=5, 12 Hz, 1H), 7.73 (ddd, J=4, 9, 12 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dihydrogen peroxide; nitric acid; In sulfuric acid; acetic anhydride; | 1. Preparation of 3-Chloro-4-nitro-pyridine-1-oxide Aqueous 30% H2O2 (60 mL) is added dropwise to a magnetically stirred solution of 3-chloro-pyridine (12 g, 105 mmol) in acetic anhydride (60 mL) under cold conditions (0 to 10 C.). The resulting mixture is allowed to warm up to room temperature slowly and then stirred overnight at room temperature. The reaction mixture is quenched with water (50 mL), diluted with toluene and concentrated to obtain the crude N-oxide as an oil in near quantitative yield. Fuming H2SO4 (25 mL) is added dropwise to a solution of crude 3-chloro-pyridine-1-oxide in concentrated H2SO4 (25 mL) under cold conditions (0 C.) with stirring. HNO3 (fuming, 90%, 60 mL) is added carefully to the above mixture with caution to keep the offset of any exotherm under control, and then allowed to warm to room temperature slowly. The resulting mixture is then heated at 120 C. for 4 h with stirring, cooled, poured into ice-cold water, and extracted with CHCl3. The combined organic phase is washed successively with saturated aqueous NaHCO3, water, brine, dried over Na2SO4, and concentrated in vacuo to afford 3-Chloro-4-nitro-pyridine-1-oxide as an yellow solid. 1H NMR (300 MHz, CDCl3): delta 8.31 (d, J=1.5 Hz, 1H), 8.13 (dd, J=1.5, 5.4 Hz, 1H), 7.95 (d, J=7.2 Hz, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
181 mg (92%) | With potassium fluoride;palladium diacetate; In tetrahydrofuran; | EXAMPLE 43 Synthesis of 3-(3-acetylphenyl)pyridine An oven dried resealable Schlenk tube was evacuated and backfilled with argon and charged with palladium acetate (2.2 mg, 0.01 mmol, 1.0 mol percent), 2-(di-tert-butylphosphino)biphenyl (6.0 mg, 0.020 mmol, 2.0 mol percent), 3-acetylphenylboronic acid (246 mg, 1.5 mmol), and potassium fluoride (173 mg, 3.0 mmol). The tube was evacuated and backfilled with argon, and THF (1 mL) and 3-chloropyridine (0.095 mL, 1.0 mmol) were added through a rubber septum. The tube was sealed with a teflon screwcap, and the reaction mixture was heated to 50° C. with stirring until the starting aryl chloride had been completely consumed as judged by GC analysis. The reaction mixture was then diluted with ether (30 mL) and poured into a separatory funnel. The mixture was washed with water (20 mL), and the aqueous layer was extracted with ether (20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel to afford 181 mg (92percent) of the title compound. |
181 mg (92%) | With potassium fluoride;palladium diacetate; In tetrahydrofuran; | Example 43 Synthesis of 3-(3-acetylphenyl)pyridine An oven dried resealable Schlenk tube was evacuated and backfilled with argon and charged with palladium acetate (2.2 mg, 0.01 mmol, 1.0 mol percent), 2-(di-tert-butylphosphino)biphenyl (6.0 mg, 0.020 mmol, 2.0 mol percent), 3-acetylphenylboronic acid (246 mg, 1.5 mmol), and potassium fluoride (173 mg, 3.0 mmol). The tube was evacuated and backfilled with argon, and THF (1 mL) and 3-chloropyridine (0.095 mL, 1.0 mmol) were added through a rubber septum. The tube was sealed with a teflon screwcap, and the reaction mixture was heated to 50° C. with stirring until the starting aryl chloride had been completely consumed as judged by GC analysis. The reaction mixture was then diluted with ether (30 mL) and poured into a separatory funnel. The mixture was washed with water (20 mL), and the aqueous layer was extracted with ether (20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel to afford 181 mg (92percent) of the title compound. |
Tags: 626-60-8 synthesis path| 626-60-8 SDS| 626-60-8 COA| 626-60-8 purity| 626-60-8 application| 626-60-8 NMR| 626-60-8 COA| 626-60-8 structure
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H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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