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[ CAS No. 1206799-15-6 ] {[proInfo.proName]}

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Chemical Structure| 1206799-15-6
Chemical Structure| 1206799-15-6
Structure of 1206799-15-6 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1206799-15-6 ]

CAS No. :1206799-15-6 MDL No. :MFCD23160048
Formula : C30H22F2N6O3 Boiling Point : -
Linear Structure Formula :- InChI Key :QHADVLVFMKEIIP-UHFFFAOYSA-N
M.W : 552.53 Pubchem ID :44603533
Synonyms :
LY2801653

Calculated chemistry of [ 1206799-15-6 ]

Physicochemical Properties

Num. heavy atoms : 41
Num. arom. heavy atoms : 32
Fraction Csp3 : 0.07
Num. rotatable bonds : 7
Num. H-bond acceptors : 7.0
Num. H-bond donors : 2.0
Molar Refractivity : 149.79
TPSA : 106.83 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.36 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.41
Log Po/w (XLOGP3) : 4.66
Log Po/w (WLOGP) : 6.4
Log Po/w (MLOGP) : 4.08
Log Po/w (SILICOS-IT) : 5.1
Consensus Log Po/w : 4.73

Druglikeness

Lipinski : 1.0
Ghose : None
Veber : 0.0
Egan : 1.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -6.32
Solubility : 0.000266 mg/ml ; 0.000000482 mol/l
Class : Poorly soluble
Log S (Ali) : -6.63
Solubility : 0.000129 mg/ml ; 0.000000234 mol/l
Class : Poorly soluble
Log S (SILICOS-IT) : -10.53
Solubility : 0.0000000162 mg/ml ; 0.0 mol/l
Class : Insoluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 3.71

Safety of [ 1206799-15-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1206799-15-6 ]

* 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 [ 1206799-15-6 ]

[ 1206799-15-6 ] Synthesis Path-Downstream   1~32

  • 1
  • [ 1206801-36-6 ]
  • [ 1206799-15-6 ]
YieldReaction ConditionsOperation in experiment
78% EXAMPLE 1 N-(3-Fluoro-4-(1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yloxy)phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide To a 100 mL round bottom flask is added tert-butyl 4-(5-(4-amino-2-fluorophenoxy)-1-methyl-1H-indazol-6-yl)-1H-pyrazole-1-carboxylate (1.43 g, 3.38 mmol), 1-(4-flurorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid (1.25 g, 5.07 mmol), EDCI (1.48 g, 7.6 mmol) and HOBt (776 mg, 5.07 mmol) followed by DMF (15 mL, 193.99 mmol) and then DIPEA (1.47 mL, 8.44 mmol). The mixture is allowed to stir at RT overnight. The reaction mixture is diluted into EtOAc (300 mL) and washed with saturated aqueous sodium chloride (5×100 mL). The combined aqueous solution is extracted with EtOAc (1×100 mL) and then the combined organic solutions are dried over N2SO4, filtered, and concentrated to dryness. The solid is purified on a silica gel column eluting with DCM (A) and a 10% MeOH in a DCM solution (B), gradient from 100% (A) to 80% (A):20% (B) over 70 min to give tert-butyl 4-(5-(2-fluoro-4-(1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)-1-methyl-1H-indazol-6-yl)-1H-pyrazole-1-carboxylate as a gold solid (2.20 g, 87% yield). MS (m/z): 653. (M+H), 675 (M+Na).To a round bottom flask is added tert-butyl 4-(5-(2-fluoro-4-(1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)-1-methyl-1H-indazol-6-yl)-1H-pyrazole-1-carboxylate (1.92 g, 2.94 mmol) and DCM (50 mL) followed by triethylsilane (1.88 mL, 11.77 mmol) and TFA (17.8 mL, 235.35 mmol). The reaction mixture is allowed to stir at RT for 1.5 hours. The solvent is removed and diluted into DCM (150 mL) and washed with saturated aqueous NaHCO3 solution (2×100 mL). The organic solution is dried with Na2SO4, and concentrated under reduced pressure to give a solid material. The solid is purified on a silica gel column eluting with DCM (A) abd a 10% MeOH in DCM solution (B), gradient from 100% (A) to 75%(A):25%(B) over 70 min, held at this 75:25 ratio for 15 min to give the title compound as an off-white solid. The solid is dissolved in hot EtOH (50 mL) followed by a portion-wise addition of distilled water (250 mL) causing a white solid to precipitate. The solid is filtered over a Buchner funnel and washed with distilled water (3×15 mL), air dried, and vacuum dried at 60 C. for 15 hours to give the title compound as an off-white solid (1.27 g, 78% yield). MS (m/z): 552.8 (M+H).
  • 2
  • N-(3-fluoro-4-(1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yloxy)phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide hydrochloride [ No CAS ]
  • [ 1206799-15-6 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; In dichloromethane; water; at 20.0℃; for 0.5h;pH 9.4; tert-Butyl 4-(5-(2-fluoro-4-(1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)-1-methyl-1H-indazol-6-yl)-1H-pyrazole-1-carboxylate (423.9 g, 649.50 mmol) is dissolved in DCM (4.24 L). HCl in MeOH (5.74 N, 799.99 mL, 4.59 mol) is added and the solution is heated at 30 C. for 1 hour. Then the reaction mixture is heated to 45 C. and DCM (1.5 L) is added. After two hours, the solution is heated to 50 C. and DCM (2 L) is added. After 3 hours, DCM (2 L) is added followed by HCl in MeOH (4.5 N, 721.67 mL, 3.25 mol). After another 45 min, DCM (1 L), HCl in MeOH (4.5 N, 288.67 mL, 1.30 mol), and MeOH (1.5 L) are added. The reaction solution is then heated to 60 C. After 4 hours, MeOH (2 L) is added and 10 min later DCM (1 L) is added followed by HCl in MeOH (4.5 N, 200 mL). After 5 hours, the reaction is complete. The reaction mixture is concentrated to about volume. MeOH (2 L) is added and the solution is concentrated to a thick slurry. Again, MeOH (2 L) is added and the mixture is concentrated to a thick slurry. The slurry is cooled to about 10-15 C. and then filtered. The solids are washed with MeOH. The solids are placed in a 55 C. vacuum oven for 2 days to give the desired product N-(3-fluoro-4-(1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yloxy)phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide hydrochloride (377 g, 92.8%). MS (m/z): 551.0 (M-H).To a 22 L round bottom flask equipped with mechanical stirring under nitrogen is added N-(3-fluoro-4-(1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yloxy)phenyl)-1-(4fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide hydrochloride (267 g, 0.62 mol) followed by DCM (7.34 L) and water (7.34 L). Na2CO3 (181.6 g, 1.71 mol) is added and the mixture is stirred at RT for 30 min. The pH is checked and found to be about 9.4. The mixture is filtered over polypropylene. The solids are collected and placed into a 5 L round bottom flask. A 20% water/MeOH solution (2.6 L) is added and the slurry is stirred for 30 min. The slurry is filtered and the solids are washed with 20% water/MeOH (600 mL). The solids are placed in a vacuum oven at 35 C. overnight. The first weighing indicates 394 g (theoretical yield 324.8 g, about 121% mass recovery). TGA (Thermogravimetric analysis)/DSC (differential scanning calorimetry) shows about 17 wt % free water and 10-11 wt% volatile loss at the melt. The solids are dried at 55 C. in a vacuum oven with a N2 sweep for 3.5 hours (354.7 g, about 109% mass recovery, NMR shows about 9.3 wt % DCM). No free water is present according to TGA/DSC. The material is sent for milling.The jet mill (Aljet 0101) in a glove bag is assembled inside a walk in hood and hooked up to N2 to a 100 lb header. The inlet pusher nozzle is adjusted for maximum draw and max nitrogen flow is introduced into the mill. Pressure readings are noted as 90 psi on pusher nozzle and 85 psi on both grind nozzles. The starting material (353.4 g) is slowly fed to the mill inlet, stopping to empty the receiver sock as needed. The total milling time is 22 min and 25 second. The calculated feed rate is 15.8 g/min (353.4 grams divided by 22.42 min). The milled material (335.7 g, 95%) is obtained with 17.7 g loss. Particle size analysis result of the milled material is d90 of 4.6 microns.TGA/DSC indicates about 11.4 wt % volatiles at the melt and NMR (DMSO) shows about 9.3 wt % DCM. 1H NMR (DMSO) delta 12.94 (br s, 1 H), 11.88 (s, 1 H), 8.44 (d, J=7.47 Hz, 1 H), 8.12 (br s, 1 H), 8.00 (br s, 1 H), 7.96 (s, 1 H), 7.94 (d, J=2.2 Hz, 1 H), 7.91 (d, J=2.6 Hz, 1H), 7.87 (s, 1H), 7.47-7.37 (m, 5 H), 6.82 (t, J=9.26 Hz, 8.82 Hz, 1 H), 6.65 (d, J=7.49 Hz, 1 H), 4.04 (s, 3 H), 2.03 (s, 3 H). LC/MS: (M+H) 553.1.
  • 4
  • [ 1206800-42-1 ]
  • [ 1206799-15-6 ]
  • 5
  • [ 1206800-56-7 ]
  • [ 1206799-15-6 ]
  • 13
  • 1-(2,4-dibromo-5-(2-fluoro-4-nitrophenoxy)benzylidene)-2-methylhydrazine [ No CAS ]
  • [ 1206799-15-6 ]
  • 25
  • C14H11BrFN3O [ No CAS ]
  • [ 1206799-15-6 ]
  • 30
  • C18H18FNO4 [ No CAS ]
  • 4-((6-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)-1-methyl-1H-indazol-5-yl)oxy)-3-fluoroaniline [ No CAS ]
  • [ 1206799-15-6 ]
  • 31
  • N-(4-((6-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)-1-methyl-1H-indazol-5-yl)oxy)-3-fluorophenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide [ No CAS ]
  • [ 1206799-15-6 ]
  • 32
  • 6-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)-5-(2-fluoro-4-nitrophenoxy)-1-methyl-1H-indazole [ No CAS ]
  • [ 1206799-15-6 ]
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