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[ CAS No. 99368-68-0 ] {[proInfo.proName]}

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Chemical Structure| 99368-68-0
Chemical Structure| 99368-68-0
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Product Details of [ 99368-68-0 ]

CAS No. :99368-68-0 MDL No. :MFCD11101042
Formula : C6H4ClF3N2 Boiling Point : -
Linear Structure Formula :- InChI Key :UMEYJHZYKYUOEQ-UHFFFAOYSA-N
M.W : 196.56 Pubchem ID :13532244
Synonyms :

Calculated chemistry of [ 99368-68-0 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.17
Num. rotatable bonds : 1
Num. H-bond acceptors : 4.0
Num. H-bond donors : 1.0
Molar Refractivity : 38.65
TPSA : 38.91 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.06 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.37
Log Po/w (XLOGP3) : 2.02
Log Po/w (WLOGP) : 3.5
Log Po/w (MLOGP) : 1.52
Log Po/w (SILICOS-IT) : 2.33
Consensus Log Po/w : 2.14

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.64
Solubility : 0.455 mg/ml ; 0.00232 mol/l
Class : Soluble
Log S (Ali) : -2.46
Solubility : 0.675 mg/ml ; 0.00343 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.17
Solubility : 0.132 mg/ml ; 0.000673 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.93

Safety of [ 99368-68-0 ]

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 [ 99368-68-0 ]

* 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 [ 99368-68-0 ]
  • Downstream synthetic route of [ 99368-68-0 ]

[ 99368-68-0 ] Synthesis Path-Upstream   1~10

  • 1
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YieldReaction ConditionsOperation in experiment
92% With iron; ammonium chloride In ethanol; water at 80℃; for 4 h; To a solution of 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (10.0 g, 44.1 mmol) in ethanol:water:TH F tin (2:2:1, 150 mL) were added, NH4CI (16.53 g, 309 mmol) and iron powder (17.26 g, 309 mmol). The resulting reaction mixture was stirred at 80eC for 4 h. After completion of the reaction, the reaction mixture was cooled to room temprature, filtered over celite bed and filtrate bed was washed with ethyl acteate (200 mL). Combined filtrate was concentrated to afford 8.0 g (92percent) of the titled product as a brown solid. 1HNMR (400 MHz, DMSO-d6) U7.93 (d, J = 2.7 Hz, 1H), 7.39 (d, J = 2.8 Hz, 1H), 6.02 (s, 2H); ESI-MS (m/z) 197.26 (MH)+.
92% With hydrogen In ethyl acetate for 20 h; C. 6-Chloro-5-(trifluoromethyl)pyridin-3-amine A mixture of 2-chloro-5-nitro-3-(trifiuoromethyi)pyridine (5.25 rnrnoi, 1.1S g), ZnBr2 (1.05 mmol, 0.200 g) and 5percent Pt (C) (1.58 mmol, 0.31 g) in ethyl acetate (50 ml) was stirred for 20 hours under hydrogen atmosphere. The catalyst was filtered off and the solid was washed with warmed ethanol. The solvent was evaporated affording the expected product (0.95 g, yield 92percent). 1H NMR (300 MHz, DMSO-d6) δ ppm: 5.59 (bs, 1 H), 7.37 (s, 1 H), 7.92 (s, 1 H). C. 6-Chloro-5-(trifluoromethyl)pyridin-3-amine <n="71"/>A mixture of 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (5.25 mmol, 1.19 g), ZnBr2 (1.05 mmol, 0.200 g) and 5percent Pt .(C). (1.58 mmol, 0.31 g) in ethyl acetate (50 ml) was stirred for 20 hours under hydrogen atmosphere. The catalyst was filtered off and the solid was washed with warmed ethanol. The solvent was evaporated affording the expected product (0.95 g, yield 92percent). δ 1H NMR (300 MHz1 DMSO-d6): 5.59 (bs, 1 H)1 7.37 (s, 1 H), 7.92 (s, 1H).
65% With water; iron; ammonium chloride In methanol at 20℃; for 4.08333 h; Reference Example 119 6-chloro-5-(trifluoromethyl)pyridine-3-amine; Reduced iron (1.3 g) and ammonium chloride (2.1 g) were added to water (40 mL), and the mixture was stirred at room temperature for 5 min. A solution of 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (1.8 g) in methanol (40 mL) was added, and the mixture was stirred at room temperature for 1 hr. Reduced iron (2.3 g) was added, and the mixture was further stirred at the same temperature for 3 hr. The reaction mixture was filtered through celite, and celite was washed with ethyl acetate. The filtrate was extracted with ethyl acetate, and the extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1-->1:1) to give the title compound as a solid (yield 1.0 g, 65percent). 1H-NMR (CDCl3) δ: 7.29 (1H, m), 7.99 (1H, m), 2H not detected.
51.9% at 80℃; for 0.25 h; To a mixture of 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (2 g, 8.83 mmol) in acetic acid (10 mL) was added iron (2.465 g, 44.1 mmol) in one portion. The mixture was stirred at 80° C. for 15 min. The mixture was filtered and concentrated and then washed with aq. NaOH and extracted with EA. he crude material was purified by silica column chromatography (PE/EA=5:1). All fractions found to contain product by TLC (PE/EA=8:1, Rf=0.6) were combined and concentrated to yield a yellow solid of 6-chloro-5-(trifluoromethyl)pyridin-3-amine (1 g, 4.58 mmol, 51.9percent yield): 1H NMR (400 MHz, CD3OD) δ 8.06 (s, 1H), 7.86 (d, J=8.60 Hz, 1H), 7.53 (d, J=8.60 Hz, 1H), 7.46-7.26 (m, 5H), 4.16-4.11 (m, 2H), 3.81 (s, 2H), 1.47 (t, J=6.62 Hz, 3H); ES-LCMS m/z 197.0 (M+H).
51.9% at 80℃; for 0.25 h; To a mixture of 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (2 g, 8.83 mmol) in acetic acid (10 inL) was added iron (2.465 g, 44.1 mmol) in one portion. The mixture was stirred at 80 °C for 15 min. The mixture was filtered and concentrated and then washed with aqueous NaOH and extracted with EA. The crude material was purified by silica column chromatography (PE/EA = 5: 1). All fractions found to contain product by TLC (PE/EA = 8: 1, Rf = 0.6) were combined and concentrated to yield a yellow solid of 6-chloro-5-(trifluoromethyl)pyridin-3 -amine (1 g, 4.58 mmol, 51.9percent yield): lH NMR (400 MHz, CD3OD) δ 8.06 (s, 1H), 7.86 (d, J = 8.60 Hz, 1H), 7.53 (d, J = 8.60 Hz, 1H), 7.46-7.26 (m, 5H), 4.16-4.11 (m, 2H), 3.81 (s, 2H), 1.47 (t, J = 6.62 Hz, 3H); ES-LCMS m/z 197.0 (M+H).
51.9% at 80℃; for 0.25 h; To a mixture of 2-chloro-5-nitro-3- (trifluoromethyl) pyridine (2 g 8.83 mmol) in AcOH (10 mL) was added iron (2.465 g 44.1 mmol) in one portion. The mixture was stirred at 80 for 15 min. The mixture was filtered and concentrated and then washed with aq. NaOH and extracted with EA. The residue was purified by silica column chromatography (PE/EA 51) . All fractions found to contain product by TLC (PE/EA 81 Rf 0.6) were combined and concentrated to yield a yellow solid of 6-chloro-5- (trifluoromethyl) pyridin-3-amine (1 g 4.58 mmol 51.9yield) 1HNMR(400 MHz CD3OD) δ 8.06 (s 1H) 7.86 (d J 8.60 Hz 1H) 7.53 (d J 8.60 Hz 1H) 7.46-7.26 (m 5H) 4.16-4.11 (m 2H) 3.81 (s 2H) 1.47 (t J 6.62 Hz 3H) ES-LCMS m/z 197.0 (M+H)

Reference: [1] Patent: WO2018/20474, 2018, A1, . Location in patent: Page/Page column 309-310
[2] Patent: WO2009/21696, 2009, A1, . Location in patent: Page/Page column 38; 69-70
[3] Patent: US2007/60623, 2007, A1, . Location in patent: Page/Page column 39
[4] Patent: US2014/275111, 2014, A1, . Location in patent: Paragraph 0280; 0281
[5] Patent: WO2014/141187, 2014, A1, . Location in patent: Page/Page column 60
[6] Patent: WO2016/37578, 2016, A1, . Location in patent: Page/Page column 84
[7] Patent: WO2006/42289, 2006, A2, . Location in patent: Page/Page column 52
[8] Patent: US2006/223837, 2006, A1, . Location in patent: Page/Page column 41
[9] Patent: JP2016/11315, 2016, A, . Location in patent: Paragraph 0061-0062
[10] Patent: US9388159, 2016, B2, . Location in patent: Page/Page column 15; 16
  • 2
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Reference: [1] Patent: WO2009/21696, 2009, A1,
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Reference: [1] Patent: WO2009/21696, 2009, A1,
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Reference: [1] Patent: US2004/77605, 2004, A1,
  • 5
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Reference: [1] Patent: US2014/275111, 2014, A1,
[2] Patent: WO2014/141187, 2014, A1,
[3] Patent: WO2016/37578, 2016, A1,
  • 6
  • [ 99368-66-8 ]
  • [ 99368-68-0 ]
Reference: [1] Patent: US2014/275111, 2014, A1,
[2] Patent: WO2014/141187, 2014, A1,
[3] Patent: WO2016/37578, 2016, A1,
  • 7
  • [ 65753-47-1 ]
  • [ 99368-68-0 ]
Reference: [1] Patent: JP2016/11315, 2016, A,
[2] Patent: US9388159, 2016, B2,
  • 8
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Reference: [1] Patent: JP2016/11315, 2016, A,
[2] Patent: US9388159, 2016, B2,
  • 9
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Reference: [1] Patent: JP2016/11315, 2016, A,
[2] Patent: US9388159, 2016, B2,
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Reference: [1] Patent: US9388159, 2016, B2,
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