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[ CAS No. 1034305-17-3 ] {[proInfo.proName]}

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Chemical Structure| 1034305-17-3
Chemical Structure| 1034305-17-3
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Product Details of [ 1034305-17-3 ]

CAS No. :1034305-17-3 MDL No. :MFCD28144826
Formula : C15H10BrFS Boiling Point : -
Linear Structure Formula :- InChI Key :IKGTVOQAJKYBGO-UHFFFAOYSA-N
M.W : 321.21 Pubchem ID :66608287
Synonyms :

Calculated chemistry of [ 1034305-17-3 ]

Physicochemical Properties

Num. heavy atoms : 18
Num. arom. heavy atoms : 15
Fraction Csp3 : 0.07
Num. rotatable bonds : 2
Num. H-bond acceptors : 1.0
Num. H-bond donors : 0.0
Molar Refractivity : 78.94
TPSA : 28.24 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -4.22 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.27
Log Po/w (XLOGP3) : 5.69
Log Po/w (WLOGP) : 5.81
Log Po/w (MLOGP) : 5.41
Log Po/w (SILICOS-IT) : 6.63
Consensus Log Po/w : 5.36

Druglikeness

Lipinski : 1.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -5.9
Solubility : 0.000404 mg/ml ; 0.00000126 mol/l
Class : Moderately soluble
Log S (Ali) : -6.05
Solubility : 0.000287 mg/ml ; 0.000000894 mol/l
Class : Poorly soluble
Log S (SILICOS-IT) : -7.37
Solubility : 0.0000136 mg/ml ; 0.0000000424 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.48

Safety of [ 1034305-17-3 ]

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 [ 1034305-17-3 ]

* 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 [ 1034305-17-3 ]
  • Downstream synthetic route of [ 1034305-17-3 ]

[ 1034305-17-3 ] Synthesis Path-Upstream   1~9

  • 1
  • [ 1034305-17-3 ]
  • [ 761423-87-4 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 10, p. 3263 - 3279
[2] Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 1064 - 1070
[3] Patent: CN108276396, 2018, A,
  • 2
  • [ 1034305-17-3 ]
  • [ 761423-87-4 ]
Reference: [1] Patent: CN105541816, 2016, A,
  • 3
  • [ 1034305-17-3 ]
  • [ 951382-34-6 ]
Reference: [1] Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 1064 - 1070
[2] Patent: CN108276396, 2018, A,
  • 4
  • [ 1034305-11-7 ]
  • [ 1034305-17-3 ]
YieldReaction ConditionsOperation in experiment
90.1% With triethylsilane; boron trifluoride diethyl etherate In dichloromethane at -20℃; for 0.5 h; Will 35.4g (105mmol)Benzo[b]thiophene-2-methanol, α-(5-bromo-2-fluorophenyl) (compound of formula 3) is solubleIn 800 mL of dichloromethane,And cooled to -20 ° C,To this solution was added 36.5 mL (230 mmol)Triethylsilane and 15.2 mL (120 mmol) of boron trifluoride etherate,The mixture was stirred at -20 ° C for 30 minutes.A saturated aqueous solution of sodium hydrogencarbonate was added to the reaction mixture.The organic phase was separated and dried over magnesium sulfate.It is then filtered and dried under vacuum.The obtained crude product was purified by column chromatography (ethyl acetate-hexane).Obtaining benzo[b]thiophene,2-[(5-Bromo-2-fluorophenyl)methyl](Compound 4) 30.4g;purity99.5percent; yield 90.1percent;
64% With triethylsilane; boron trifluoride diethyl etherate In dichloromethane at -20℃; for 0.5 h; General procedure: To a cold (-78 °C) solution of 50 (16.6 g, 124 mmol) in THF (200 mL) was added n-BuLi (1.60 M in hexane; 78.5 mL, 124 mmol) and the mixture was stirred at -78 °C for 1.5 h. To the reaction mixture was added a solution of 64 (29.0 g, 118 mmol) in THF (300 mL) and the mixture was stirred at -78 °C for 2 h. To the reaction mixture was added H2O and Et2O and the organic layer was separated, dried over MgSO4, filtered and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (EtOAc-hexane) to give alcohol as a pale yellow oil. To a cold (-20 °C) solution of this oil (43.3 g, 114 mmol) in CH2Cl2 (800 mL) was added Et3SiH (36.5 mL, 229 mmol) and BF3*OEt2 (15.2 mL, 120 mmol) and the mixture was stirred at -20 °C for 30 min. To the reaction mixture was added saturated aqueous sodium bicarbonate solution and the organic layer was separated, dried over MgSO4, filtered and evaporated in vacuo. The resulting residue was purified by column chromatography on silica gel (EtOAc-hexane) to give the title compound (66) (35.6 g, 86percent) as a pale yellow oil.
41 g With trifluoroacetic acid; HSiPh3 In hexane at -10 - 0℃; for 1 h; Inert atmosphere Under nitrogen protection, in a four-necked flask equipped with a mechanical stirring and a thermometer, 20.1 g of benzothiophene and 180 mL of 2-methyltetrahydrofuran were stirred and dissolved, and the temperature was lowered to -40--35 ° C, and 90 ml of butyllithium was added thereto. 3 hours after the reaction at the temperature, 40.3 g of 2-fluoro-5-bromobenzaldehyde was added. After the reaction was completed at this temperature for 10 hours, the temperature was raised to room temperature, and the pH was adjusted to 7 by adding hydrochloric acid. 2. Under a nitrogen atmosphere, Compound 2 and n-hexane were added to a four-necked flask equipped with a mechanical stirring and a thermometer, and the mixture was stirred and dissolved. Then, trifluoroacetic acid and triphenylsilane (5 eq) were added, and then reacted at -10 ° C for 1 hour. After the completion of the monitoring reaction, the temperature was raised to room temperature, and the target compound was obtained as a white solid, 41 g.The yield in two steps was 81percent.
Reference: [1] Patent: CN108276396, 2018, A, . Location in patent: Paragraph 0041; 0048; 0049; 0064; 0079
[2] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 10, p. 3263 - 3279
[3] Patent: CN108623558, 2018, A, . Location in patent: Paragraph 0042; 0044; 0046; 0048; 0050; 0052; 0054; 0056
  • 5
  • [ 1034305-19-5 ]
  • [ 1034305-17-3 ]
YieldReaction ConditionsOperation in experiment
80.9%
Stage #1: With sodium tetrahydroborate; sodium hydroxide In water; acetonitrile at 40 - 67.9℃;
Stage #2: With hydrogenchloride In water; toluene; acetonitrile
Third step: Synthesis of 2-(5-bromo-2-fluorobenzyl)-1-benzothiophene; Acetonitrile (1,260 ml)was added to 2-[(5-bromo-2-fluorophenyl)(chloro)methyl]-1-benzothiophene (265.69 g) and the mixture was heated to 40°C. The resulting solution was added to a water (1,260 ml) solution of sodium borohydride (113.0 g) and sodium hydroxide (14.9 g) at 59.0 to 67.9°C, followed by stirring at 24.1 to 67.5°C for 17.5 hours. To the reaction mixture were added 36percent hydrochloric acid (340.5 g), water (1,260 ml) and toluene (1,260 ml), and extraction was conducted. The organic layer was washed with a 5percent aqueous sodium hydrogencarbonate solution (1,260 ml) and subjected to vacuum distillation to distil off the solvent. To the residue were added 2-propanol (378 ml) and methanol (756 ml), and the residue was dissolved with heating. To the solution was added, as a seed crystal, 2.7 g of the 2-(5-bromo-2-fluorobenzyl)-1-benzothiophene produced by the method of Reference Example 2, at 39.7°C, followed by stirring at 0.7 to 5.0°C for 13 hours. The separated-out crystals were collected by filtration, washed with methanol (251 ml), and vacuum-dried to obtain, as white crystals, 2-(5-bromo-2-fluorobenzyl)-1-benzothiophene [194.05 g, yield: 80.9percent, purity: 99percent (HPLC)]. 1H-NMR (CDCl3): δ 4.18 (2H, s), 6.90-6.97 (1H, dd), 7.17 (1H, s), 7.22-7.40 (4H, m), 7.67 (1H, d), 7.74 (1H, d)
Reference: [1] Patent: EP2105442, 2009, A1, . Location in patent: Page/Page column 14
  • 6
  • [ 93777-26-5 ]
  • [ 1034305-17-3 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 10, p. 3263 - 3279
[2] Patent: CN108276396, 2018, A,
  • 7
  • [ 95-15-8 ]
  • [ 1034305-17-3 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 10, p. 3263 - 3279
[2] Patent: CN108276396, 2018, A,
  • 8
  • [ 67-56-1 ]
  • [ 1034305-17-3 ]
  • [ 32469-28-6 ]
  • [ 1034305-23-1 ]
YieldReaction ConditionsOperation in experiment
86.4%
Stage #1: With n-butyllithium; butyl magnesium bromide In tetrahydrofuran; hexane; toluene at -16 - -12℃; for 1 h;
Stage #2: at -15 - -12℃; for 3 h;
Stage #3: With methanesulfonic acid In tetrahydrofuran; hexane; toluene at 20℃; for 16 h;
A solution of 0.9M n-butyl magnesium chloride in tetrahydrofuran (0.9M, 7.3mL) was added to toluene (18.0mL) at -16 ° C and a solution of n-butyl lithium in n-hexane was added dropwise at -12~-16 ° C (2.66 M, 4.9 mL) and stirred at -12 to -15 ° C for 16 minutes.2- (5-bromo-2-fluorobenzyl) -1-benzothiophene (Compound I, 2.000 g) at -12 to -15 ° C,Of a toluene solution (10.0 mL)The reaction solution was dropped,At -12 to -16 ° CStir for one hour.A solution of 2,3,4,6-di-O- (trimethylsilyl) -D-glucono-1,5-lactone (Compound II, 3.197g) in toluene (10.0 ML) was added dropwise to the reaction solution, and the mixture was stirred at -12 to -15 ° C for 3 hours.The reaction mixture was poured into a methanol solution (10.0 mL) of methanesulfonic acid (3.0 mL) at 0 ° C or less, and the mixture was stirred at room temperature for 16 hours and 36 minutes. The reaction mixture was quenched by the addition of an aqueous sodium carbonate solution at a pH of about 8.The organic layer was washed with saturated brine (10 mL, once) and dried over anhydrous sodium sulfate, and extracted with ethyl acetate (50 mL, twice). After filtration, the filtrate was distilled off under reduced pressure, and the title compound (2.336 g, yield 86.4percent) was isolated from the obtained residue by silica gel column chromatography.
Reference: [1] Patent: TW2016/2128, 2016, A, . Location in patent: Paragraph 0024; 0025
[2] Patent: EP2105442, 2009, A1, . Location in patent: Page/Page column 14
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  • [ 1034305-23-1 ]
Reference: [1] Patent: CN107540706, 2018, A,
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