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[ CAS No. 978-62-1 ] {[proInfo.proName]}

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Chemical Structure| 978-62-1
Chemical Structure| 978-62-1
Structure of 978-62-1 * Storage: {[proInfo.prStorage]}
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Product Details of [ 978-62-1 ]

CAS No. :978-62-1 MDL No. :MFCD00218820
Formula : C15H8ClF6NO2 Boiling Point : -
Linear Structure Formula :- InChI Key :CHILCFMQWMQVAL-UHFFFAOYSA-N
M.W :383.67 Pubchem ID :5081913
Synonyms :
IMD-0354

Calculated chemistry of [ 978-62-1 ]

Physicochemical Properties

Num. heavy atoms : 25
Num. arom. heavy atoms : 12
Fraction Csp3 : 0.13
Num. rotatable bonds : 5
Num. H-bond acceptors : 8.0
Num. H-bond donors : 2.0
Molar Refractivity : 77.69
TPSA : 49.33 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 : No
Log Kp (skin permeation) : -4.51 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.75
Log Po/w (XLOGP3) : 5.82
Log Po/w (WLOGP) : 7.45
Log Po/w (MLOGP) : 4.69
Log Po/w (SILICOS-IT) : 4.89
Consensus Log Po/w : 5.12

Druglikeness

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

Water Solubility

Log S (ESOL) : -5.91
Solubility : 0.000471 mg/ml ; 0.00000123 mol/l
Class : Moderately soluble
Log S (Ali) : -6.63
Solubility : 0.0000907 mg/ml ; 0.000000236 mol/l
Class : Poorly soluble
Log S (SILICOS-IT) : -6.66
Solubility : 0.0000832 mg/ml ; 0.000000217 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 2.07

Safety of [ 978-62-1 ]

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 [ 978-62-1 ]

* 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 [ 978-62-1 ]
  • Downstream synthetic route of [ 978-62-1 ]

[ 978-62-1 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 321-14-2 ]
  • [ 328-74-5 ]
  • [ 978-62-1 ]
YieldReaction ConditionsOperation in experiment
85.5% With phosphorus trichloride In toluene for 3 h; Heating / reflux A mixture of 5-chlorosalicylic acid(6.90g, 40mmol), 3,5-bis(trifluoromethyl)aniline(9.16g, 40mmol), phosphorus trichloride(1.74mL, 20mmol) and toluene(80mL) was refluxed for 3 hours under argon atmosphere. After the reaction mixture was cooled to room temperature, it was diluted with ethyl acetate(240mL). After the ethyl acetate layer was washed successively with water and brine, dried over anhydrous magnesium sulfate, the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel(n-hexane:ethyl acetate=4:1) to give the title compound(13.12g, 85.5percent) as a light yellow solid.1H-NMR(DMSO-d6): δ 7.05(1H, d, J=8.7Hz), 7.49(1H, dd, J=8.7, 2.7Hz), 7.85(1H, s), 7.87(1H, d, J=2.7Hz), 8.45(2H, s), 10.85(1H, s), 11.39(1H, s).
62% With phosphorus trichloride In chlorobenzeneMicrowave irradiation General procedure: All salicylanilides(1a-8d) were synthesized via a previously described microwave assisted (MicroSYNTH Milestone) method.25 Briefly,the appropriately substituted salicylic acid (1 eq) and the substituted aniline (1 eq) were suspended or dissolved in chlorobenzene(1 mL/0.15 mmol of acid). Phosphorus trichloride (PCl3) was added(0.5 eq) and the mixture was stirred (600 rpm) and radiated(530 W) for 30–60 min. The mixture was filtrated while hot and was let cool, initially at r.t. and overnight at 4 °C. The formed pre-cipitate was filtered and recrystallized with ethanol or mixture of hexane/AcOEt in order to afford the final compounds with yields of 41–83percent.
57% With trichlorophosphate In toluene for 6 h; Inert atmosphere; Reflux To 30 ml and of toluene were added 5-chlorosalicylic acid (862 mg, 5 mmol), 3,5-bis(trifluoromethyl)aniline (1.37 g, 6 mmol), and phosphoroustrichloride (755 mg, 5.5 mmol) in the presence of argon gas, followed by stirring for 6 hours through heat-reflux.
Sodium hydrogen carbonate was added to the mixture to adjust pH to 7, followed by concentration under reduced pressure.
The mixture was dissolved in 60 ml and of ethylacetate, which was washed with water (40 ml*2).
The organic layer was concentrated under reduced pressure, followed by column chromatography to give 1.09 g of the target compound (yield: 57percent).
m.p: 172-173° C.;
1H-NMR (300 MHz, DMSO-d6): δ 7.05 (1H, d, J=8.7 Hz), 7.49 (1H, dd, J=8.7, 2.7 Hz), 7.85 (1H, s), 7.87 (1H, d, J=2.7 Hz), 8.45 (2H, s), 10.85 (1H, s), 11.39 (1H, s).
28% With pyridine; phosphorus trichloride In toluene for 12 h; Inert atmosphere; Reflux General procedure: The salicylic acid (1.2 equiv) was added to a mixture of toluene (0.3 M), aniline (1.0 equiv), phosphorus trichloride (1.1 equiv), and pyridine (0.05 equiv) in a Radley’s Carousel reaction tube (modified from Itai et al.20). The mixture was refluxed under nitrogen for 12 h then cooled to room temperature. Aqueous sodium bicarbonate was added dropwise to attain pH 6–7. The resultant mixture was extracted with EtOAc. The organic extracts were combined, dried (MgSO4), and concentrated under vacuum. After chromatography (1:10 EtOAc:Hex) compounds were recrystallized (EtOAc/Hex).
28% With pyridine; phosphorus trichloride In tolueneInert atmosphere; Reflux Phosphorus trichloride (0.13ml, 1.5mmol) was added to a stirred solution of 3,5-bis(trifluoromethyl)aniline (0.47ml, 3mmol), a catalytic amount of pyridine and 5-chloro salicylic acid (621.3mg, 3.6mmol) in anhydrous toluene (10ml) in in a Radley’s Carousel reaction tube under an argon atmosphere. After the reaction mixture was refluxed for overnight, it was cooled to room temperature and aq. sodium bicarbonate was added dropwise until PH=6 - 7. After extracting with ethyl acetate, the organic layers was dried, dried (MgSO4) and concentrated in vacuo. After chromatography (EA-Hex, 1:10) of the crude product, and followed by recrystalization from EtOAc/hexane provided 2a as a white solid (320mg, 28percent). mp 172 - 173 oC. 1H NMR (DMSO-d6) δ 11.37(brs, 1H), 10.91(s, 1H), 8.43(s, 2H), 7.85-7.88(m, 2H), 7.49(dd, J1=8.7Hz, J2=2.9Hz, 1H), 7.05(d, J=8.7Hz, 1H).

Reference: [1] Patent: EP1352650, 2003, A1,
[2] Patent: EP1512397, 2005, A1, . Location in patent: Page/Page column 77
[3] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 4, p. 1524 - 1532
[4] Patent: US2014/221411, 2014, A1, . Location in patent: Paragraph 0192; 0193
[5] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 1, p. 114 - 126
[6] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 6, p. 1748 - 1751
[7] Journal of Medicinal Chemistry, 2012, vol. 55, # 19, p. 8375 - 8391,17
[8] Journal of Medicinal Chemistry, 2012, vol. 55, # 19, p. 8375 - 8391
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