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[ CAS No. 653-92-9 ] {[proInfo.proName]}

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Chemical Structure| 653-92-9
Chemical Structure| 653-92-9
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Product Details of [ 653-92-9 ]

CAS No. :653-92-9 MDL No. :MFCD06204026
Formula : C8H6BrFO2 Boiling Point : -
Linear Structure Formula :- InChI Key :JENBPOJAZCPSEW-UHFFFAOYSA-N
M.W : 233.03 Pubchem ID :7210837
Synonyms :

Calculated chemistry of [ 653-92-9 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.12
Num. rotatable bonds : 2
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 45.38
TPSA : 26.3 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) : -5.88 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.28
Log Po/w (XLOGP3) : 2.6
Log Po/w (WLOGP) : 2.8
Log Po/w (MLOGP) : 3.09
Log Po/w (SILICOS-IT) : 2.79
Consensus Log Po/w : 2.71

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.16
Solubility : 0.161 mg/ml ; 0.000691 mol/l
Class : Soluble
Log S (Ali) : -2.8
Solubility : 0.368 mg/ml ; 0.00158 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.61
Solubility : 0.0569 mg/ml ; 0.000244 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.52

Safety of [ 653-92-9 ]

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 [ 653-92-9 ]

* 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.

  • Upstream synthesis route of [ 653-92-9 ]
  • Downstream synthetic route of [ 653-92-9 ]

[ 653-92-9 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 1006-41-3 ]
  • [ 74-88-4 ]
  • [ 653-92-9 ]
YieldReaction ConditionsOperation in experiment
98% With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 23℃; for 48 h; Inert atmosphere DBU (1.7 equiv, 1.16 mL, 7.76 mmol) was added to a solution of 2-bromo-4-fluorobenzoicacid (1.0equiv, 1.0 g, 4.57 mmol) and iodomethane (2.0 equiv, 0.57 mL, 9.14 mmol) in CH3CN(11 mL) at 23 °C. After stirring for 48 h, the reaction was quenched with H2O(10 mL) and extracted with Et2O (2 x 10 mL). The combined organicextracts were washed with water (20 mL), brine (20 mL), dried over Na2SO4and filtrated. Evaporation of the solvent under reduced pressure followed byflash chromatography (SiO2, 95/5 hexane/EtOAc) afforded 1.0 g (98percent)of the entitled ester as a colorless oil. Rf = 0.50 (95/5 hexane/EtOAc);1H NMR (400 MHz, CDCl3, 25 °C): d 7.88(dd, J = 8.8, 6.0 Hz, 1H), 7.41 (dd, J = 8.3, 2.5 Hz, 1H), 7.08 (ddd, J = 8.8,7.6, 2.5 Hz, 1H), 3.92 (s, 3H) ppm.
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 20, p. 4393 - 4398
[2] Patent: US6407250, 2002, B1,
[3] Patent: US6511999, 2003, B2,
[4] Patent: US2002/128233, 2002, A1,
[5] Patent: US2004/162323, 2004, A1,
[6] Patent: US2005/65200, 2005, A1,
[7] Patent: US6369089, 2002, B1,
  • 2
  • [ 67-56-1 ]
  • [ 1006-41-3 ]
  • [ 653-92-9 ]
YieldReaction ConditionsOperation in experiment
88.3% for 4 h; Reflux To a solution of 2-bromo-4-fluorobenzoic acid (2.17 g, 10.00 mmol) in methanol (10 mL) was added sulfuric acid (1.63 mL, 30 mmol) , the reaction mixture was refluxed for 4 h.The solvent was removed in vacuo.The mixture was diluted with diethyl ether, and washed water (50 mL * 3) and brine (50 mL * 3), dried over MgSO4. The solvent was removed under reduced pressure.The residue was purified by flash column chromatography with petroleum ether-ethyl acetate (80/1) as eluant to afford colorless liquid. Yield: 88.3percent.This compound was prepared according to the general procedure reported by Baker.13 The spectral data were consistent with that reported in the literature.
86% at 60℃; for 10 h; To a mixture of 2-bromo-4-fluorobenzoic acid 1 (2.19 g, 10 mmol) in MeOH (20 mL) was added SOCl2 (0.5 mL) dropwise at rt. The resulting mixture was stirred at 60°C for 10 h. The mixture was concentrated to give the title compound (2 g, 86percent>) as brown oil. MS (ESI): m/z = 232.8 [M + H]+.
37% at 0℃; for 19 h; Heating / reflux Intermediate Preparation 21 2-Bromo-4-fluoro-benzoic acid methyl esterTo a solution of thionyl chloride (2.6 mL, 35.7 mmol) in methanol (500 mL) at 0 0C is added 4-fluoro-2-bromo benzoic acid (5.18 g, 23.6 mmol). The mixture is heated to reflux for 19 h. The mixture is concentrated and purified via flash chromatography on silica (120 g) using a gradient of 0 to 80percent ethyl acetate in heptane to provide the title compound (2.06 g, 37percent) as an oil. MS m/z 233.0 (M+l)
Reference: [1] Tetrahedron Letters, 2007, vol. 48, # 23, p. 4123 - 4126
[2] Patent: WO2005/58826, 2005, A1, . Location in patent: Page/Page column 100
[3] Angewandte Chemie - International Edition, 2013, vol. 52, # 28, p. 7177 - 7180
[4] Journal of Organic Chemistry, 2013, vol. 78, # 13, p. 6735 - 6745
[5] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 24, p. 7101 - 7111
[6] Patent: WO2015/48662, 2015, A2, . Location in patent: Page/Page column 124
[7] Synthesis (Germany), 2012, vol. 44, # 14, p. 2173 - 2180
[8] Patent: WO2009/12125, 2009, A1, . Location in patent: Page/Page column 26
[9] Patent: WO2006/25783, 2006, A1, . Location in patent: Page/Page column 98-100
[10] Tetrahedron, 2016, vol. 72, # 24, p. 3454 - 3467
[11] Patent: WO2018/89449, 2018, A1, . Location in patent: Page/Page column 175-179
  • 3
  • [ 1006-41-3 ]
  • [ 653-92-9 ]
YieldReaction ConditionsOperation in experiment
88% With thionyl chloride In methanol at 70℃; for 2 h; To a 250-mL row1d-bottom flask was added a solution of 2-bromo-4-fluorohenzoicacid J 01 a (1 0 g, 45.66 rnmol, 1.0 equiv.) in methanol (l 00 mL) Thionyl chloride (16 2 g,137.29 mmoL 3.0 equiv.) vvas added dropvvise. The resulting mixture vvas stirred at 70°C for2h, and then quenched ,.vith the addition of water/ice. The aqueous mixture was extracted5 v\~th ethyl acetate (lOO mL x 2). The combined organic extracts vvere washed brine (50 rnL x2), concentrated to a crude solid, which was further purified by silica gel columnchromatography eluting with ethyl acetate/petroleum ether (0percent-8°1()). Removal of solventsafforded methy 12-bromo-4-fluorobenzoate 101 b (9.4 g, 88percent) as a colorless solid.
Reference: [1] Patent: WO2018/39386, 2018, A1, . Location in patent: Page/Page column 229; 230
  • 4
  • [ 1006-41-3 ]
  • [ 18107-18-1 ]
  • [ 653-92-9 ]
YieldReaction ConditionsOperation in experiment
99% at 20℃; for 3 h; A.
2-Bromo-4-fluoro-benzoic acid methyl ester.
To a solution of 2-bromo-4-fluoro-benzoic acid (10.95 g, 50 mmol) in toluene/MeOH (3:1; 200 mL) was added trimethylsilyidiazomethane (2 M in hexanes; 36 mL, 71.7 mmol) at RT for 3 h.
The mixture was diluted with EtOAc (300 mL) and washed sequentially with satd. aq. NaHCO3 (50 mL) and brine (50 mL), dried (MgSO4), and concentrated to provide 11.5 g (99percent) of the crude material which was used in the next step without further purification. 1H NMR (500 MHz, CDCl3): 7.86 (dd, J=8.8, 6.0, 1H), 7.39 (dd, J=8.3, 2.5, 2H), 7.08-7.05 (m, 1H), 3.91 (s, 3H).
Reference: [1] Patent: US2006/223810, 2006, A1, . Location in patent: Page/Page column 28
  • 5
  • [ 496-69-5 ]
  • [ 79-22-1 ]
  • [ 653-92-9 ]
Reference: [1] Patent: US4427438, 1984, A,
[2] Patent: US4437877, 1984, A,
[3] Patent: US4431822, 1984, A,
  • 6
  • [ 653-92-9 ]
  • [ 544-92-3 ]
  • [ 127510-96-7 ]
YieldReaction ConditionsOperation in experiment
94%
Stage #1: for 1.25 h; Heating / reflux
Stage #2: With sodium cyanide In DMF (N,N-dimethyl-formamide); water
(b) Methyl 2-cyano-4-fluorobenzoate; Methyl 2-bromo-4-fluorobenzoate (1.0 g, 4.29 mmol; see step (a) above) was dissolved in dry DMF (5 mL) and degassed with N2-gas for 5 minutes. CuCN (769 mg, 8.58 mmol) was added and mixture was degassed again before the temperature was raised. The reaction mixture was refluxed for 75 minutes. NaCN (aq, 10percent) was added and the mixture was extracted with DCM. The DCM phase was dried through a phase separator and the solvent was removed in vacuo. The crude product was dissolved in toluene and washed once with water. The organic phase was dried over MgS04 and filtered. The solvent was removed in vacuo to give the product (in 94percent yield), which was used without further purification. 'H NMR (500 MHz, CDC13) 5 4.01 (s, 3H), 7.35-7. 42 (m, 1H), 7.52 (dd, 1H), 8.15-8. 23 (m, 1H)
Reference: [1] Patent: WO2005/58826, 2005, A1, . Location in patent: Page/Page column 100
  • 7
  • [ 653-92-9 ]
  • [ 127510-96-7 ]
YieldReaction ConditionsOperation in experiment
39% at 140℃; Inert atmosphere To a 250-mL round-bottom flask purged and maintained under an inert atmosphere ofnitrogen, was added methyl2-bromo-4-fluorobenzoate 101 b (4 g, 17.16 mmol, 1.0 equiv.)andN';N-dimethylformamide (20 mL). Solid CuCN (2.3 g, 25.84 mmol, 1.5 equiv.) wasadded in several batches. The resulting mixture vvas stirred at l40°C overnight. Upon coolingto room temperature, the mixture '.vas quenched with water. The aqueous mixture was15 extracted with ethyl acetate (100 mL x 3), and the combined organic extracts were washedwith t-hO (50 mL x 2) and brine (80 mL x 2) Removal of solvents gave a residue which waspmitl.ed by silica gel column chromatography eluting with ethyl acetate/petroleum ether(lOpercent) to provide methyl2-cyano-4-t1uorobenzoate 101c (1.2g, 39percent) as a white solid
850 mg at 120℃; for 1.5 h; Inert atmosphere To a solution of methyl 2-bromo-4-fluorobenzoate (1.2 g, 5.15 mmol) in DMF (5 mL) was added cyanocopper (0.92 g, 10.3 mmol) under N2. The reaction was stirred at 120 °C for 1.5 h under N2. Then, the reaction was cooled to room temperature.10percent NaCN (10 mL) was added to the reaction. The mixture was extracted with DCM (3 x 30 mL). The layers were separated and the organic phase was washed with saturated aqueous NaCl (3 x 50 mL) .The combined organic layers were dried over Na2SO4. After filtration, 850 mg of product was obtained as a white solid.
Reference: [1] Patent: WO2018/39386, 2018, A1, . Location in patent: Page/Page column 229; 230
[2] Patent: WO2018/26371, 2018, A1, . Location in patent: Paragraph 0158; 0260
  • 8
  • [ 653-92-9 ]
  • [ 1260666-80-5 ]
Reference: [1] Patent: WO2018/26371, 2018, A1,
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