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[ CAS No. 155377-05-2 ] {[proInfo.proName]}

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Chemical Structure| 155377-05-2
Chemical Structure| 155377-05-2
Structure of 155377-05-2 * Storage: {[proInfo.prStorage]}
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Product Details of [ 155377-05-2 ]

CAS No. :155377-05-2 MDL No. :MFCD02090527
Formula : C8H6F3NO2 Boiling Point : -
Linear Structure Formula :- InChI Key :AYABEJGGSWJVPN-UHFFFAOYSA-N
M.W : 205.13 Pubchem ID :45158822
Synonyms :

Calculated chemistry of [ 155377-05-2 ]

Physicochemical Properties

Num. heavy atoms : 14
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.25
Num. rotatable bonds : 3
Num. H-bond acceptors : 6.0
Num. H-bond donors : 0.0
Molar Refractivity : 40.52
TPSA : 39.19 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) : -6.16 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.79
Log Po/w (XLOGP3) : 1.96
Log Po/w (WLOGP) : 3.04
Log Po/w (MLOGP) : 1.4
Log Po/w (SILICOS-IT) : 2.24
Consensus Log Po/w : 2.09

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.47
Solubility : 0.702 mg/ml ; 0.00342 mol/l
Class : Soluble
Log S (Ali) : -2.41
Solubility : 0.802 mg/ml ; 0.00391 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.99
Solubility : 0.208 mg/ml ; 0.00101 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.68

Safety of [ 155377-05-2 ]

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 [ 155377-05-2 ]

* 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 [ 155377-05-2 ]
  • Downstream synthetic route of [ 155377-05-2 ]

[ 155377-05-2 ] Synthesis Path-Upstream   1~10

  • 1
  • [ 67-56-1 ]
  • [ 201230-82-2 ]
  • [ 39890-95-4 ]
  • [ 155377-05-2 ]
YieldReaction ConditionsOperation in experiment
96% at 60℃; for 17 h; Add palladium(II) acetate (200 mg, 2 w/wpercent) and l,l '-bis(diphenylphosphino)ferrocene (dppf) (400 mg, 4 w/wpercent) to a solution of 2-chloro-6-trifluoromethyl-pyridine (10.0 g, 55.1 mmol) in methanol (30 mL). To the orange solution add triethylamine (8.45 mL, 60.6 mmol). Purge the mixture with nitrogen and then maintain under an atmosphere of carbon monoxide (40 psig) at 60 0C for 17 h. Cool to ambient temperature and concentrate under a reduced pressure. Dissolve the solid in tert-butylmethyl ether (70 mL). Filter the resulting slurry over silica gel (10 g) and diatomaceous earth (10 g).Concentrate the filtrate to afford the title compound as a light orange solid (10.8 g, 96percent). 1H NMR (399.84 MHz, DMSO d6): 8.31-8.27 (m, IH), 8.14 (dd, J= 2.4, 6.4 Hz, 2H), 3.91 (s, 3H). HRMS (ESI) m/z (M+H)+ calcd for C8H7F3NO2: 206.0423, found 206.0422.
Reference: [1] Patent: WO2009/131814, 2009, A2, . Location in patent: Page/Page column 45
[2] Patent: US2015/18328, 2015, A1, . Location in patent: Paragraph 0720-0721
[3] Patent: WO2015/3640, 2015, A1, . Location in patent: Page/Page column 156
  • 2
  • [ 67-56-1 ]
  • [ 131747-42-7 ]
  • [ 155377-05-2 ]
YieldReaction ConditionsOperation in experiment
21 g for 14 h; Reflux To a solution of 6-trifluoromethyl-pyridine-2-carboxylic acid (22 g, 1 equiv.) in methanol (200 mL) was added concentrated H2S04 (0.3 mL). The mixture was stirred at reflux for 14 hours and then cooled to ambient. Solid NaHCO3 (10 g) was added and the suspension was stirred for 30 minutes. The mixture was filtered and the filtrate was concentrated to remove the volatile. The crude product was diluted with ethyl acetated (200 mL) and dried with anhydrous Na2504. The mixture was filtered and concentrated to give 6-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (2) as a waxy solid (21 g).
Reference: [1] Patent: WO2015/18060, 2015, A1, . Location in patent: Page/Page column 48
[2] Patent: WO2015/17821, 2015, A2, . Location in patent: Page/Page column 67
[3] Patent: WO2016/53850, 2016, A1, . Location in patent: Paragraph 00270; 00277
[4] Patent: WO2016/126798, 2016, A1, . Location in patent: Page/Page column 72; 73
[5] Patent: WO2017/24134, 2017, A1, . Location in patent: Paragraph 0073; 0074
[6] Patent: WO2017/66611, 2017, A1, . Location in patent: Paragraph 0560
[7] Patent: WO2017/69878, 2017, A1, . Location in patent: Paragraph 00104; 00105
[8] Patent: US2018/64715, 2018, A1, . Location in patent: Paragraph 0205
[9] Patent: WO2018/64119, 2018, A1, . Location in patent: Paragraph 1344
[10] Patent: US2018/311249, 2018, A1, . Location in patent: Paragraph 0344
  • 3
  • [ 67-56-1 ]
  • [ 201230-82-2 ]
  • [ 189278-27-1 ]
  • [ 155377-05-2 ]
YieldReaction ConditionsOperation in experiment
67% at 60℃; for 18 h; Inert atmosphere Step 1:
Methyl 6-trifluoromethyl-pyridine-2-carboxylate
Under the protection of nitrogen gas, to a solution of 2-bromo-6-trifluoromethylpyridine (1.48 g, 6.55 mmol) in methanol (50.0 mL) were successively added palladium acetate (74.0 mg, 0.33 mmol), 1,1'-bis(diphenylphosphino)ferrocene (363.0 mg, 0.655 mmol) and triethylamine (0.92 g, 9.8 mmol), and reacted at a temperature of 60 °C for 18 hours under carbon monoxide atmosphere (2 atm).
After the reaction was complete, the reaction solution was cooled to room temperature, and filtered.
The filtrate was concentrated in vacuo, and the resulting residue was purified by column chromatography on silica gel to afford methyl 6-trifluoromethyl-pyridine-2-carboxylate (0.9 g, yield 67.0percent).
Reference: [1] Patent: EP3330258, 2018, A1, . Location in patent: Paragraph 0077-0078
  • 4
  • [ 26218-75-7 ]
  • [ 155377-05-2 ]
Reference: [1] Organic Letters, 2014, vol. 16, # 6, p. 1744 - 1747
  • 5
  • [ 26218-75-7 ]
  • [ 155377-05-2 ]
Reference: [1] Chemistry - A European Journal, 2016, vol. 22, # 6, p. 2075 - 2084
  • 6
  • [ 26218-75-7 ]
  • [ 155377-05-2 ]
Reference: [1] RSC Advances, 2016, vol. 6, # 79, p. 75465 - 75469
  • 7
  • [ 186581-53-3 ]
  • [ 124-38-9 ]
  • [ 368-48-9 ]
  • [ 155377-05-2 ]
Reference: [1] European Journal of Organic Chemistry, 2003, # 8, p. 1569 - 1575
  • 8
  • [ 368-48-9 ]
  • [ 155377-05-2 ]
Reference: [1] Patent: US2018/311249, 2018, A1,
  • 9
  • [ 108-19-0 ]
  • [ 155377-05-2 ]
  • [ 1446507-38-5 ]
YieldReaction ConditionsOperation in experiment
71%
Stage #1: at 30 - 35℃; Large scale
Stage #2: With titanium(IV) tetraethanolate In ethanol at 30 - 35℃; Large scale
Stage #3: With sodium ethanolate In ethanol at 55 - 65℃; for 3 h; Large scale
100801 Mixture of methyl 6-(trifluoromethyl)picolinate (50g, 244 mmol, 1.0 eq.) and biuret (30.2 g, 293 mmol, 1.20 eq.) in 750 mL EtOH was stirred at 30-35°C for 10-20 mm. Titanium tetraethoxide (Ti(OEt)4, 27.8g, 122 mmol, 0.5 eq.) was added and stirred at 30-35°C for 30-60 mi EtONa solution in EtOH (350 g, 19percent wt, 978 mmol, 4.0 eq.) was added, and the reaction mixture was heated at 55-65°C for 3 hours. The reaction mixture was concentrated, cooled to room temperature, and diluted with 700 mL water. Concentrated HC1 solution was added to adjust pH value to pH1. Methylene chloride (DCM, 700 mL) was charged, and the slurry was stirred 20-30°C for 5-7 hours. Solid was collected by filtration, and the cake was sequentially washed twice with 6N HC1, twice with water, and once with DCM. The wet cake was dried at 50-60°C under vacuum, yielding 6-(6-(trifluoromethyl)pyridin-2-yl)- 1,3 ,5-triazine-2,4( 1H,3H)- dione as off-white solid (45.0 g, 174 mmol, 71percent yield).
47.5% With sodium ethanolate In ethanol for 2 h; Reflux; Inert atmosphere Step 2:
6-(6-trifluoromethylpyridin-2-yl)-1,3,5-triazine-2,4(1H,3H)-dione
Under the protection of nitrogen gas, to a solution of sodium ethoxide (11.2 g, 165.0 mmol) in ethanol (200 mL) were successively added methyl 6-trifluoromethyl-pyridine-2-carboxylate (10.0 g, 48.7 mmol) and biuret (4.2 g, 40.7 mmol).
The reaction mixture was heated at reflux for 2 hours, and then cooled to room temperature.
The reaction solution was concentrated in vacuo, and the resulting residue was poured into water, and adjusted to pH 7 with 6 mol/L HCl solution.
After the resulting solid was filtered, the filter cake was washed with water, and then dried to afford 6-(6-trifluoromethylpyridin-2-yl)-1,3,5-triazine-2,4(1H,3H)-dione (5.0 g, yield 47.5percent).
Reference: [1] Patent: WO2017/24134, 2017, A1, . Location in patent: Paragraph 0073; 0075; 0079; 0080; 0082
[2] Patent: EP3330258, 2018, A1, . Location in patent: Paragraph 0079-0080
[3] Patent: US2015/18328, 2015, A1, . Location in patent: Paragraph 0722-0723
[4] Patent: WO2015/3640, 2015, A1, . Location in patent: Page/Page column 156; 157
[5] Patent: WO2015/18060, 2015, A1, . Location in patent: Page/Page column 48-49
[6] Patent: WO2015/17821, 2015, A2, . Location in patent: Page/Page column 67; 68
[7] Patent: WO2016/53850, 2016, A1, . Location in patent: Paragraph 00271; 00278
[8] Patent: WO2016/126798, 2016, A1, . Location in patent: Page/Page column 73
[9] Patent: WO2017/66611, 2017, A1, . Location in patent: Paragraph 0561
[10] Patent: US2018/64715, 2018, A1, . Location in patent: Paragraph 0206
[11] Patent: US2018/311249, 2018, A1, . Location in patent: Paragraph 0345
  • 10
  • [ 155377-05-2 ]
  • [ 1446502-11-9 ]
Reference: [1] Patent: WO2015/18060, 2015, A1,
[2] Patent: WO2015/17821, 2015, A2,
[3] Patent: WO2016/53850, 2016, A1,
[4] Patent: WO2016/126798, 2016, A1,
[5] Patent: WO2017/24134, 2017, A1,
[6] Patent: WO2017/24134, 2017, A1,
[7] Patent: WO2017/66611, 2017, A1,
[8] Patent: US2018/64715, 2018, A1,
[9] Patent: US2018/311249, 2018, A1,
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