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[ CAS No. 787-69-9 ] {[proInfo.proName]}

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Chemical Structure| 787-69-9
Chemical Structure| 787-69-9
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Product Details of [ 787-69-9 ]

CAS No. :787-69-9 MDL No. :MFCD00017248
Formula : C16H14O2 Boiling Point : -
Linear Structure Formula :- InChI Key :YSTSBXDVNKYPTR-UHFFFAOYSA-N
M.W : 238.28 Pubchem ID :301558
Synonyms :

Calculated chemistry of [ 787-69-9 ]

Physicochemical Properties

Num. heavy atoms : 18
Num. arom. heavy atoms : 12
Fraction Csp3 : 0.12
Num. rotatable bonds : 3
Num. H-bond acceptors : 2.0
Num. H-bond donors : 0.0
Molar Refractivity : 72.27
TPSA : 34.14 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.28 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.33
Log Po/w (XLOGP3) : 2.07
Log Po/w (WLOGP) : 3.76
Log Po/w (MLOGP) : 2.76
Log Po/w (SILICOS-IT) : 4.29
Consensus Log Po/w : 3.04

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.92
Solubility : 0.289 mg/ml ; 0.00121 mol/l
Class : Soluble
Log S (Ali) : -2.42
Solubility : 0.914 mg/ml ; 0.00384 mol/l
Class : Soluble
Log S (SILICOS-IT) : -5.59
Solubility : 0.000608 mg/ml ; 0.00000255 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.48

Safety of [ 787-69-9 ]

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 [ 787-69-9 ]

* 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 [ 787-69-9 ]
  • Downstream synthetic route of [ 787-69-9 ]

[ 787-69-9 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 787-69-9 ]
  • [ 4072-67-7 ]
YieldReaction ConditionsOperation in experiment
96% at 20 - 50℃; for 24 h; 2-Bromo-1-[4'-(2-bromo-acetyl)-biphenyl-4-yl]ethanone
A solution of bromine (13.4 g, 4.32 mL, 83.9 mmol) in glacial acetic acid (30 mL) was added drop wise to a mixture of 1,1-(biphenyl-4-4-diyl)diethanone (10.0 g, 42.0 mmol) in glacial acetic acid (100 mL) at 50 C.
After addition was complete, the mixture was stirred at room temperature for 24 hours.
The solid was filtered and washed with chloroform to afford 1,1-(biphenyl-4,4-diyl)-bis(2-bromoethanone as white solid, (15.9 g, 96percent).
1H NMR (400 MHz, DMSO-d6) δ ppm 4.98 (s, 4H) 7.85-8.25 (m, 8H).
92%
Stage #1: With trimethylsilyl trifluoromethanesulfonate; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.25 h;
Stage #2: With N-Bromosuccinimide In dichloromethane at 0℃; for 2 h;
Taking 4.4-diacetyl biphenyl (40g, 0.17mol) and DIPEA (49g, 0.38mol) is dissolved in 1000 ml of methylene chloride, 0 °C dropwise TMSOTf (0.39mol), the drop finishes stirring 15 minutes, dropping NBS (73g, 0.41mol) in dichloromethane (200 ml) solution, the drop finishes 0 °C stirring reaction 2h, the reaction is complete, system is poured into 500 ml water, layered, dry anhydrous sodium sulfate, filtered, concentrated to remove dichloromethane, produced intermediate 1 crude, toluene crystallization get 62g solid, yield 92percent;
86% With bromine In dichloromethane at 20℃; for 6.75 h; Cooling with ice A solution of Br2 (2.7 g, 17 mmol) in CH2Cl2 (10 mL) was added dropwise over 5 min to an ice water cooled solution of 1,1'-([1,1'-biphenyl]-4,4'-diyl)diethanone 1 (2.0 g, 8.4 mmol) in CH2Cl2 (40 mL). The cooling bath was removed 40 min later, and stirring was continued at ambient temperature for 6 h. The cake of solid that formed was filtered, washed with CH2Cl2 and dried in vacuo to aord 2 (2.86 g, 86 percent) as off-white solid.
82% With bromine In dichloromethane at 20℃; for 20 h; EXAMPLES; Preparation of Compound (3); A 1 L, 3-neck round bottom flask, fitted with a nitrogen line, overhead stirrer and thermocouple, was charged with 20 g (83.9 mmol, 1 equiv) 1,1'-(biphenyl-4,4'-diyl)diethanone, 200 mL CH2Cl2 and 8.7 mL (27.1 g, 169.3 mmol, 2.02 quiv) bromine. The mixture was allowed to stir under nitrogen for about 20 hours under ambient conditions. The resulting slurry was charged with 200 mL CH2Cl2 and concentrated down to about 150 mL via vacuum distillation. The slurry was then solvent exchanged into tetrahydrofuran (THF) to a target volume of 200 mL via vacuum distillation. The slurry was cooled to 20-25° C. over 1 hour and allowed to stir at 20-25° C. for an additional hour. The off-white crystalline solids were filtered and washed with 150 mL CH2Cl2. The product was dried under vacuum at 60° C. to yield 27.4 g (69.2 mmol, 82percent) of the desired product: 1H NMR (400 MHz, CDCl3) δ 7.95-7.85 (m, 4H), 7.60-7.50 (m, 4H), 4.26 (s, 4H); 13C NMR (100 MHz, CDCl3) δ 191.0, 145.1, 133.8, 129.9, 127.9, 30.8; IR (KBr, cm-1) 3007, 2950, 1691, 1599, 1199; Anal calcd for C16H12Br2O2: C, 48.52; H, 3.05; Br, 40.34. Found: C, 48.53; H, 3.03; Br, 40.53. HRMS calcd for C16H13Br2O2 (M+H; DCI+): 394.9282. Found: 394.9292. mp 224-226° C.
82% With bromine In dichloromethane at 20℃; for 20 h; Inert atmosphere A l L, 3 -neck round bottom flask, fitted with a nitrogen line, overhead stirrer and thermocouple was charged with 20 g (83.9 mmol, 1 equiv) l,l'-(biphenyl-4,4'- diyl)diethanone, 200 mL CH2Cl2 and 8.7 mL (27. Ig, 169.3 mmol, 2.02 quiv) bromine. The mixture was allowed to stir under nitrogen for about 2Oh under ambient conditions. The resulting slurry was charged with 200 mL CH2Cl2 and concentrated down to about 150 mL via vacuum distillation. The slurry was then solvent exchanged into THF to a target volume of 200 mL via vacuum distillation. The slurry was cooled to 20-25 0C over Ih and allowed to stir at 20-25 0C for an additional hour. The off-white crystalline solids were filtered and washed with 150 mL CH2Cl2. The product was dried under vacuum at 60 0C to provide 27.4 g (69.2 mmol, 82percent) of the desired product: 1H NMR (400 MHz, CDCl3) δ 7.95-7.85 (m, 4H), 7.60-7.50 (m, 4H), 4.26 (ss 4H); 13C NMR (100 MHz, CDCl3) δ 191.0, 145.1, 133.8, 129.9, 127.9, 30.8; IR (KBr9 cm-1) 3007, 2950, 1691, 1599, 1199; Anal calcd for C16H12Br2O2: C, 48.52; H, 3.05; Br, 40.34. Found: C, 48.53; H, 3.03; Br, 40.53. HRMS calcd for C16H13Br2O2 (M + H; DCI+): 394.9282. Found: 394.9292. mp 224-226 0C.
82% With bromine In dichloromethane at 20℃; for 20 h; Inert atmosphere In a 1 L 3-neck round bottom flask equipped with a nitrogen line, overhead stirrer and thermocouple 20 g (83.9 mmol, 1 equivalent) of 1,1 '- (biphenyl-4,4'-diyl) diethanone, 200 mL CH2Cl2 and 8.7 mL (27.1 g, 169.3 mmol, 2.02 equivalents) bromine. The mixture was stirred under nitrogen for about 20 hours under ambient conditions. To the resulting slurry was added 200 mL CH2Cl2 and concentrated to about 150 mL by vacuum distillation. The slurry was then solvent exchanged to a target volume of 200 mL with THF via vacuum distillation. The slurry was cooled to 20-25 [deg.] C over 1 hour and stirred at 20-25 [deg.] C for an additional hour. The off-white crystalline solid was filtered off and washed with 150 mL CH2Cl2. The product was dried under vacuum at 60 & lt; 0 & gt; C to give 27.4 g (69.2 mmol, 82percent) of the desired product:
81% With bromine In dichloromethane Intermediate 5: 1 , 1 '-(biphenyl-4,4'-diyl)bis(2-bromoethanone); Br2 (21.6 mL, 420 mmol) in DCM (60 mL) was added dropwise to a suspension of 1,1'- (biphenyl-4,4'-diyl)diethanone (50 g, 210 mmol) in DCM (500 mL). The mixture was stirred overnight, slurry filtered of washed with DCM to give intermediate 5 (67.4 g, yield: 81percent) as a off-white solid. 1H NMR (300 MHz, CDCl3) δ ppm 8.11 (d, J= 8.4 Hz, 4H), 7.76 (d, J= 8.4 Hz, 4H), 4.49 (s, 4H).
77.5% With bromine In acetic acid at 20 - 50℃; Example 43
Compound 47
A solution of bromine (1.3 mL, 25.0 mmol) in glacial acetic acid (15 mL) was added drop-wise to a solution of 4,4'-diacetylbiphenyl (3.0 g, 12.5 mmol) in acetic acid (40 mL) at 50° C.
After the addition, the reaction mixture was stirred at room temperature overnight.
The precipitate was filtered and re-crystallized from chloroform to give 1,1'-(biphenyl-4,4'-diyl)bis(2-bromoethanone) 47 (3.84 g, 77.5percent) as a white solid. LC/MS (ESI): [M+1]+: 397.
77.5% With bromine In acetic acid at 20 - 50℃; A solution of bromine (1.3 mL, 25.0 mmol) in 15 mL glacial acetic acid was added drop-wise to a solution of 4-4'-diacetylbiphenyl (3.0 g, 12.5 mmol) in 40 mL acetic acid at 50° C. Upon completion of addition the mixture was stirred at room temperature overnight. The precipitated product was filtered off and re-crystallized from chloroform to give 1,1'-(biphenyl-4,4'-diyl)bis(2-bromoethanone) (3.84 g, 77.5percent) as a white solid.1H NMR (500 MHz, CHLOROFORM-D) δ ppm 8.09 (4 H, d, J=7.93 Hz) 7.75 (4 H, d, J=8.24 Hz) 4.47 (4 H, s)Nominal/LRMS-Anal. Calcd. for 369.07 found; (M+H)+ -397.33, (M-H)- 395.14
77.5% With bromine In acetic acid at 20 - 50℃; A solution of bromine (1.3 mL, 25.0 mmol) in 15 mL glacial acetic acid was added drop-wise to a solution of 4-4'-diacetylbiphenyl (3.0 g, 12.5 mmol) in 40 mL acetic acid at 50° C. Upon completion of addition the mixture was stirred at room temperature overnight. The precipitated product was filtered off and re-crystallized from chloroform to give 1,1'-(biphenyl-4,4'-diyl)bis(2-bromoethanone) (3.84 g, 77.5percent) as a white solid.1H NMR (500 MHz, CHLOROFORM-D) δ ppm 8.09 (4 H, d, J=7.93 Hz) 7.75 (4 H, d, J=8.24 Hz) 4.47 (4 H, s)Nominal/LRMS-Anal. Calcd. for 369.07 found; (M+H)+-397.33, (M-H)--395.14
77.5% With bromine In dichloromethane at 20 - 50℃; for 20 h; A 1 L, 3-neck round bottom flask, fitted with a nitrogen line, overhead stirrer and thermocouple was charged with 20 g (83.9 mmol, 1 equiv) 1,1'-(biphenyl-4,4'-diyl)diethanone, 200 mL CH2Cl2 and 8.7 mL (27.1 g, 169.3 mmol, 2.02 quiv) bromine. The mixture was allowed to stir under nitrogen for about 20 h under ambient conditions. The resulting slurry was charged with 200 mL CH2Cl2 and concentrated down to about 150 mL via vacuum distillation. The slurry was then solvent exchanged into THF to a target volume of 200 mL via vacuum distillation. The slurry was cooled to 20-25° C. over 1 h and allowed to stir at 20-25° C. for an additional hour. The off-white crystalline solids were filtered and washed with 150 mL CH2Cl2. The product was dried under vacuum at 60° C. to provide 27.4 g (69.2 mmol, 82percent) of the desired product: 1H NMR (400 MHz, CDCl3) δ 7.95-7.85 (m, 4H), 7.60-7.50 (m, 4H), 4.26 (s, 4H); 13C NMR (100 MHz, CDCl3) δ 191.0, 145.1, 133.8, 129.9, 127.9, 30.8; IR (KBr, cm-1) 3007, 2950, 1691, 1599, 1199; Anal calcd for C16H12Br2O2: C, 48.52; H, 3.05; Br, 40.34. Found: C, 48.53; H, 3.03; Br, 40.53. HRMS calcd for C16H13Br2O2 (M+H; DCI+): 394.9282. Found: 394.9292. mp 224-226° C.; A solution of bromine (1.3 mL, 25.0 mmol) in 15 mL glacial acetic acid was added drop-wise to a solution of 4-4'-diacetylbiphenyl (3.0 g, 12.5 mmol) in 40 mL acetic acid at 50° C. Upon completion of addition the mixture was stirred at room temperature overnight. The precipitated product was filtered off and re-crystallized from chloroform to give 1,1'-(biphenyl-4,4'-diyl)bis(2-bromoethanone) (3.84 g, 77.5percent) as a white solid.1H NMR (500 MHz, CHLOROFORM-D) δ ppm 8.09 (4H, d, J=7.93 Hz) 7.75 (4H, d, J=8.24 Hz) 4.47 (4H, s)Nominal/LRMS-Anal. Calcd. for 369.07 found; (M+H)+ -397.33, (M-H)- -395.14
75.6% at 30 - 35℃; for 16 h; Large scale 20 kg of 4,4'-diacetylbiphenyl was suspended in 400 kg of acetic acid,The temperature was raised to 30 ° C. Then 27.2 kg of bromine was added and reacted at 30-35 ° C for 16 h.After the reaction was monitored by HPLC, the filter was filtered and the filter cake was rinsed with 6 kg of chloroform,A white powder of 31 kg.The resulting crude product was recrystallized from 130 kg of tetrahydrofuran.
93 kg With bromine In acetic acid at 10℃; for 12 h; Large scale 2) 62kg of 4,4-diacetylbiphenyl was added to 400kg of acetic acid, and the temperature was lowered to 10 ° C, 120kg of bromine was added dropwise, and the reaction was incubated at 10 ° C for 12 hours.
3) After the completion of the reaction, the product was filtered, concentrated, crystallized and dried to obtain 93 kg of 4,4'-bis (2-bromoacetyl) biphenyl. After testing: Purity: 99.5percent (GC).

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[2] Patent: CN105777719, 2016, A, . Location in patent: Paragraph 0028; 0041; 0022; 0043; 0051; 0052; 0053
[3] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 14, p. 4864 - 4868
[4] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 16, p. 3147 - 3150
[5] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 17, p. 3711 - 3715
[6] Patent: US2009/43107, 2009, A1, . Location in patent: Page/Page column 7-8
[7] Patent: WO2010/138368, 2010, A1, . Location in patent: Page/Page column 147
[8] Patent: KR101508022, 2015, B1, . Location in patent: Paragraph 0129-0131
[9] Patent: WO2010/62821, 2010, A1, . Location in patent: Page/Page column 56
[10] Patent: US2011/136799, 2011, A1, . Location in patent: Page/Page column 47
[11] Patent: US2008/44379, 2008, A1, . Location in patent: Page/Page column 99
[12] Patent: US2008/44380, 2008, A1, . Location in patent: Page/Page column 100
[13] Patent: US2008/50336, 2008, A1, . Location in patent: Page/Page column 73-74; 173
[14] Patent: CN106256825, 2016, A, . Location in patent: Paragraph 0086-0088
[15] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1995, # 14, p. 1789 - 1796
[16] Ukrainskii Khimicheskii Zhurnal (Russian Edition), 1958, vol. 23, p. 93,96[17] Chem.Abstr., 1958, p. 18377
[18] Journal of medicinal chemistry, 1963, vol. 6, p. 573 - 578
[19] Journal fuer Praktische Chemie (Leipzig), 1963, vol. 22, p. 140 - 152
[20] Patent: WO2011/91532, 2011, A1, . Location in patent: Page/Page column 23
[21] Journal of Heterocyclic Chemistry, 2015, vol. 52, # 5, p. 1321 - 1330
[22] Patent: CN105967990, 2016, A, . Location in patent: Paragraph 0028; 0030; 0031
[23] Patent: WO2009/102318, 2009, A1, . Location in patent: Page/Page column 163
  • 2
  • [ 106-37-6 ]
  • [ 5720-05-8 ]
  • [ 149104-90-5 ]
  • [ 613-33-2 ]
  • [ 50670-49-0 ]
  • [ 5731-01-1 ]
  • [ 787-69-9 ]
  • [ 5748-38-9 ]
Reference: [1] Organometallics, 2014, vol. 33, # 12, p. 3108 - 3118
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