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[ CAS No. 2454397-74-9 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 2454397-74-9
Chemical Structure| 2454397-74-9
Chemical Structure| 2454397-74-9
Structure of 2454397-74-9 * Storage: {[proInfo.prStorage]}
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Product Details of [ 2454397-74-9 ]

CAS No. :2454397-74-9 MDL No. :N/A
Formula : C8H8ClFN2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :BYIJYBRHUZZBLR-UHFFFAOYSA-N
M.W : 218.61 Pubchem ID :154644444
Synonyms :

Calculated chemistry of [ 2454397-74-9 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 14
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.25
Num. rotatable bonds : 3
Num. H-bond acceptors : 4.0
Num. H-bond donors : 1.0
Molar Refractivity : 49.7
TPSA : 65.21 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) : -6.21 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.01
Log Po/w (XLOGP3) : 2.0
Log Po/w (WLOGP) : 2.06
Log Po/w (MLOGP) : 1.08
Log Po/w (SILICOS-IT) : 1.91
Consensus Log Po/w : 1.81

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.57
Solubility : 0.582 mg/ml ; 0.00266 mol/l
Class : Soluble
Log S (Ali) : -3.0
Solubility : 0.221 mg/ml ; 0.00101 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.05
Solubility : 0.195 mg/ml ; 0.000891 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.1

Safety of [ 2454397-74-9 ]

Signal Word:Warning Class:
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338 UN#:
Hazard Statements:H302-H315-H319-H335 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 2454397-74-9 ]

* 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 [ 2454397-74-9 ]

[ 2454397-74-9 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 64-17-5 ]
  • [ CAS Unavailable ]
  • [ 1801841-62-2 ]
  • [ 2454397-74-9 ]
YieldReaction ConditionsOperation in experiment
81% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine at 90℃; for 40h; Step B: 4-Amino-6-chloro-5-fluoronicotinic acid ethyl ester Compound 2-chloro-3-fluoro-5-iodopyridin-4-amine (5.4 g, 19.82 mmol), Pd(dppf)Cl (695 mg, 0.991 mmol) and triethylamine (555 mg, 49.6 mmol) were dispersed in In absolute ethanol, heated to 90 under carbon monoxide atmosphere for 40h.After the reaction was completed, the reaction solution was filtered through celite, and the filtrate was concentrated and purified by FCC (SiO 2 , EA/DCM=0-100%) to obtain ethyl 4-amino-6-chloro-5-fluoronicotinic acid as a yellow solid. Ester (3.5 g, 81% yield).
74% With bis-triphenylphosphine-palladium(II) chloride; triethylamine at 80℃; for 15h; Inert atmosphere; 15.2 Step 2 Under nitrogen protection stirring at 25 degrees CelsiusTo a solution of compound 78-1 (1 g, 3.67 mmol, 1.0 equiv) in ethanol (10 mL) was added triethylamine (1.38 g, 12.96 mmol,3.6 equiv) and dichlorobis(triphenylphosphine)palladium (266 mg, 0.36 mmol, 0.1 equiv).The mixture was reacted at 80 degrees Celsius for 15 hours in a carbon monoxide atmosphere (3 atmospheres), and the reaction process was monitored by liquid quality. After the reaction, the reaction solution was cooled to 25 degrees Celsius, filtered through celite, and the filtrate was concentrated under reduced pressure to obtain a crude product. The obtained crude product was purified by silica gel column chromatography, the mobile phase was eluted with a gradient of 0%→31% ethyl acetate/petroleum ether, and the obtained fractions were evaporated under reduced pressure to remove the solvent to obtain compound 78-2 (yellow solid, 660 mg) , yield 74%).
With bis-triphenylphosphine-palladium(II) chloride; triethylamine at 80℃; for 15h; Inert atmosphere; E [0319] Step E: To a solution of 2-chloro-3-fluoro-5-iodo-pyridin-4-amine (78.4 g, 288 mmol, 1.0 eq) in EtOH (1500 mL) was added Pd(PPh3)2Cl2 (20.2 g, 28.8 mmol, 0.1 eq) and Et3N (105 g, 1.04 mol, 144 mL, 3.61 eq) under nitrogen. The suspension was degassed under vacuum and purged with nitrogen several times. The mixture was stirred under CO (15.0 psi) at 80 °C for 15 hours. Upon completion, the mixture was filtered and the filtrate was concentrated under vacuum to remove 70% of MeOH and the residue was filtered. The combined filter cakes were concentrated under vacuum ethyl 4-amino-6-chloro-5-fluoro- pyridine-3 -carboxylate (142 g, crude) was obtained as a yellow solid. LCMS [ESI, M+l]: 219. [0320] 'H NMR (400 MHz, dmso-d6) d = 8.36 (s, 1H), 7.49 - 7.42 (m, 2H), 4.31 (q, J= 7.2 Hz, 2H), 1.31 (t, J= 7.2 Hz, 3H).
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine at 65℃; for 4h; 22.1 Step 1: A mixture of 50-1 (15 g, 55.2 mmol) , TEA (23 mL, 165.3 mmol) and Pd (dppf) Cl2(4 g, 5.52 mmol) in EtOH (150 mL) was stirred at 65 C for 4 hours under 1 atm of CO atmosphere. After being cooled to room temperature, the mixture was filtered and the filtrate was concentrated. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10/1) to afford 67-1.
81 % With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; triethylamine at 80℃; Step 4: 4-Amino-6-chloro-5-fluoronicotinic acid ethyl ester 4-Amino-2-chloro-3-fluoro-5-iodopyridine (30g, 110.3mmol, 1.0eq), triethylamine (33.4g, 330.9mmol, 3.0eq), [1,1'-bis(di(di)) Phenylphosphino)ferrocene]palladium dichloride (8.07g, 11.03mmol, 0.1eq) was dissolved in ethanol (750mL), replaced by carbon monoxide gas twice, and reacted at 80 degrees overnight under the protection of carbon monoxide, and the reaction solution was cooled to room temperature, Concentrated, the concentrated residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate/dichloromethane=5/1/1, volume ratio) to obtain 4-amino-6-chloro-5-fluoronicotinic acid ethyl ester (19.6 g, yield 81%), off-white solid.
68 g With bis-triphenylphosphine-palladium(II) chloride; triethylamine at 80℃; Step 2 To a solution of 2-chloro-3-fluoro-5-iodopyridin-4-amine (90 g, 330.33 mmol, 1 equiv) in ethanol (1700 mL) was added Pd(PPh3)2Cl2 (23 g, 33.03 mmol, 0.1 equiv) and TEA (120 g, 1189.21 mmol, 3.6 equiv) and was stirred for 15 h at 80oC under CO (15 Psi) atmosphere. The resulting mixture was filtered, the filtrate was concentrated under reduced pressure to remove 70% of ethanol and the residue was filtered. The filter cake was concentrated under reduced pressure to afford 134-h (68 g, 94.16%) as a yellow solid m/z: [M+H]+Calcd for C8H9ClFN2O2219.0;Found 219.0.

  • 2
  • [ 64-17-5 ]
  • [ 124-38-9 ]
  • [ 1801841-62-2 ]
  • [ 2454397-74-9 ]
YieldReaction ConditionsOperation in experiment
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine at 80℃; for 15h; D Step D. 4-amino-6-chloro-5-fluoro- pyridine-3-carboxylate. To a solution of 2-chloro-3- fluoro-5-iodo-pyridin-4-amine (78.4 g, 288 mmol, 1.0 eq) in EtOH (1500 mL) was added Pd(PPh3)2Cl2 (20.2 g, 28.8 mmol, 0.1 eq) and Et3N (105 g, 1.04 mol, 144 mL, 3.61 eq) under nitrogen. The suspension was degassed under vacuum and purged with nitrogen several times. The mixture was stirred under CO2 (15.0 psi) at 80 °C for 15 hours. Upon completion, the mixture was filtered, and the filtrate was concentrated under vacuum to remove 70% of MeOH and the residue was filtered. The combined filter cakes were concentrated under vacuum. ethyl 4-amino- 6-chloro-5-fluoro- pyridine-3-carboxylate (142 g, crude) was obtained as a yellow solid. LCMS [ESI, M+1]: 219.1H NMR (400 MHz, dmso-d6) d = 8.36 (s, 1H), 7.49 - 7.42 (m, 2H), 4.31 (q, J = 7.2 Hz, 2H), 1.31 (t, J = 7.2 Hz, 3H).
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine at 80℃; for 15h; Inert atmosphere; Step D. ethyl 4-amino-6-chloro-5-fluoro- pyridine-3 -carboxylate. To a solution of 2- chloro-3-fhioro-5-iodo-pyridin-4-amine (78.4 g, 288 mmol, 1.0 eq) in EtOH (1500 mL) was added Pd(PPh3)2Ch (20.2 g, 28.8 mmol, 0.1 eq) and EtsN (105 g, 1.04 mol, 144 mL, 3.61 eq) under nitrogen. The suspension was degassed under vacuum and purged with nitrogen several times. The mixture was stirred under CO2 (15.0 psi) at 80 °C for 15 hours. Upon completion, the mixture was filtered, and the filtrate was concentrated under vacuum to remove 70% of MeOH and the residue was filtered. The combined filter cakes were concentrated under vacuum, ethyl 4- amino-6-chl oro-5 -fluoro- pyridine-3 -carboxylate (142 g, crude) was obtained as a yellow solid. LCMS [ESI, M+l]: 219. ’H NMR (400 MHz, dmso-d6) 6 = 8.36 (s, 1H), 7.49 - 7.42 (m, 2H), 4.31 (q, J = 7.2 Hz, 2H), 1.31 (t, J = 7.2 Hz, 3H).
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine at 80℃; for 15h; Inert atmosphere; Step D. ethyl 4-amino-6-chloro-5-fluoro- pyridine-3 -carboxylate. To a solution of 2- chloro-3-fhioro-5-iodo-pyridin-4-amine (78.4 g, 288 mmol, 1.0 eq) in EtOH (1500 mL) was added Pd(PPh3)2Ch (20.2 g, 28.8 mmol, 0.1 eq) and EtsN (105 g, 1.04 mol, 144 mL, 3.61 eq) under nitrogen. The suspension was degassed under vacuum and purged with nitrogen several times. The mixture was stirred under CO2 (15.0 psi) at 80 °C for 15 hours. Upon completion, the mixture was filtered, and the filtrate was concentrated under vacuum to remove 70% of MeOH and the residue was filtered. The combined filter cakes were concentrated under vacuum, ethyl 4- amino-6-chl oro-5 -fluoro- pyridine-3 -carboxylate (142 g, crude) was obtained as a yellow solid. LCMS [ESI, M+l]: 219. ’H NMR (400 MHz, dmso-d6) 6 = 8.36 (s, 1H), 7.49 - 7.42 (m, 2H), 4.31 (q, J = 7.2 Hz, 2H), 1.31 (t, J = 7.2 Hz, 3H).
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); triethylamine at 80℃; for 15h; Inert atmosphere; Preparation of 4-amino-6-chloro-5-fluoronicotinic acid ethyl ester Under nitrogen atmosphere, to a solution of 2-chloro-3-fluoro-5-iodopyridin-4-amine (8.2 g, 30 mmol, 1.0 eq) in EtOH (150 mL) was added Pd(PPh3)2Cl2(2.1 g, 3 mmol ), 0.1eq) and TEA (11.1g, 0.11mmol, 3.6eq), the resulting reaction solution was reacted at 80° C. for 15 hours under a CO2atmosphere, and then filtered.The filtrate was concentrated under reduced pressure to 70-80% of the original volume and filtered again.The filter cakes were collected and combined and dried in vacuo to obtain the target product (quantitative yield).It was directly used in the next reaction without purification.

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