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[ CAS No. 654655-69-3 ] {[proInfo.proName]}

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Chemical Structure| 654655-69-3
Chemical Structure| 654655-69-3
Structure of 654655-69-3 * Storage: {[proInfo.prStorage]}
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Product Details of [ 654655-69-3 ]

CAS No. :654655-69-3 MDL No. :MFCD22493488
Formula : C17H14BrNO Boiling Point : -
Linear Structure Formula :- InChI Key :WMFHVNYOCKTDMX-UHFFFAOYSA-N
M.W : 328.20 Pubchem ID :11667032
Synonyms :

Calculated chemistry of [ 654655-69-3 ]

Physicochemical Properties

Num. heavy atoms : 20
Num. arom. heavy atoms : 16
Fraction Csp3 : 0.12
Num. rotatable bonds : 3
Num. H-bond acceptors : 2.0
Num. H-bond donors : 0.0
Molar Refractivity : 85.39
TPSA : 22.12 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -4.67 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.43
Log Po/w (XLOGP3) : 5.11
Log Po/w (WLOGP) : 4.6
Log Po/w (MLOGP) : 4.14
Log Po/w (SILICOS-IT) : 5.05
Consensus Log Po/w : 4.46

Druglikeness

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

Water Solubility

Log S (ESOL) : -5.49
Solubility : 0.00107 mg/ml ; 0.00000325 mol/l
Class : Moderately soluble
Log S (Ali) : -5.32
Solubility : 0.00158 mg/ml ; 0.0000048 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -7.58
Solubility : 0.00000871 mg/ml ; 0.0000000265 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.25

Safety of [ 654655-69-3 ]

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 [ 654655-69-3 ]

* 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 [ 654655-69-3 ]
  • Downstream synthetic route of [ 654655-69-3 ]

[ 654655-69-3 ] Synthesis Path-Upstream   1~14

  • 1
  • [ 654655-80-8 ]
  • [ 654655-69-3 ]
  • [ 10320-49-7 ]
Reference: [1] Chinese Chemical Letters, 2015, vol. 26, # 6, p. 790 - 792
  • 2
  • [ 654655-68-2 ]
  • [ 124-41-4 ]
  • [ 654655-69-3 ]
YieldReaction ConditionsOperation in experiment
96% Reflux; Inert atmosphere Compound 2 (20g, 0.06mol) was dissolved into anhydrous CH3OH (100mL), and 108g solution of CH3ONa (15percent) in CH3OH was added. The mixture was stirred and refluxed overnight. Then the mixture was cooled to room temperature and stored in refrigerator at -20°C overnight. Crude compound 3 precipitates in the form of white needles. The solid was separated with filtration, washed with water, and air dried to give 19g (96percent) of compound 3 as white solid.
33% Heating / reflux A mixture of intermediate 2 (0.233 mol) in a 30percent MeONa in MeOH solution (222.32 ml) and MeOH (776 ml) was stirred and refluxed overnight, then poured out on ice and extracted with DCM. The organic layer was separated, dried (MgS04), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: DCM/cyclohexane 20/80 and then 100/0; 20-45um). The pure fractions were collected and the solvent was evaporated, yielding 25g of intermediate 3 (33percent).
33% Heating / reflux A mixture of intermediate compound 2 (prepared according to A2) (0.233 mol) in CH3ONa (30percent) in methanol (222.32 ml) and methanol (776ml) was stirred and refluxed overnight, then poured out on ice and extracted with CH2CI2 . The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated . The residue was purified by column chromatography over silica gel (eluent:CH2Cl2/cyclohexane 20/80 and then 100/0; 20-45μm). The pure fractions were collected and the solvent was evaporated . Yield : 25g of intermediate compound 3 (Yield=33percent; mρ.84°C) as a white powder
33% Heating / reflux Preparation of intermediate compound 3 A mixture of intermediate compound 2 (prepared according to A2) (0.233 mol) in [CH30NA] (30percent) in methanol (222.32 ml) and methanol [(776ML)] was stirred and refluxed overnight, then poured out on ice and extracted with [CH2CL2.] The organic layer was separated, dried [(MGSO4),] filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: [CH2CL2/CYCLOHEXANE] 20/80 and then [100/0 ; 20-45 UM). THE] pure fractions were collected and the solvent was evaporated. Yielding: 25g of intermediate compound 3 (Yield=33percent; mp. [84C)] as a white powder.
33% Heating / reflux Example A3; Preparation of intermediate 3 Intermediate 3; A mixture of intermediate 2 (0.233 mol) in CH30Na (30percent) in MeOH (222.32 ml) and MeOH (776 ml) was stirred and refluxed overnight, then poured out on ice and extracted with CH2Cl2. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl21cyclohexane 20/80 and then 100/0; 20-45um). The pure fractions were collected and the solvent was evaporated. Yield: 25 g (33percent) of intermediate 3 (M. P.: 84 °C).
33% Heating / reflux c-3) Preparation of intermediate 19; A mixture of intermediate 11 (0.233 mol) in CH3ONa (30percent) in methanol (222.32 ml) and methanol (776 ml) was stirred and refluxed overnight, then poured out on ice and extracted with CH2CI2 . The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated . The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/cyclohexane 20/80 and then 100/0; 20-45 μm). The pure fractions were collected and the solvent was evaporated . Yield: 25 g of intermediate 19 (33percent) (melting point: 84°C).
33% Heating / reflux A mixture of intermediate 2 (0.233 mol) in CH3ONa (30percent) in MeOH (222.32 ml) and MeOH (776 ml) was stirred and refluxed overnight, then poured out on ice and extracted with CH2CI2 . The organic layer was separated, dried (MgSO/t), filtered and the solvent was evaporated . The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/cyclohexane 20/80 and then 100/0; 20-45 μm). The pure fractions were collected and the solvent was evaporated . Yield: 25 g (33percent) of intermediate 3 (M.P.: 84 0C).
33% Heating / reflux a) Preparation of intermediate 3: A mixture of intermediate 2 (0.233 mol) in a 30percent MeONa in MeOH solution (222.32 ml) and MeOH (776 ml) was stirred and refluxed overnight, then poured out on ice and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: DCM/cyclohexane 20/80 and then 100/0; 20-45 μm). The pure fractions were collected and the solvent was evaporated, yielding 25g of intermediate 3 (33percent).
33% Heating / reflux Example A3; a. Preparation of intermediate 9; A mixture of 6-bromo-2-chloro-3-(phenylmethyl)-quinoline (prepared according to the teachings in WO2005/070924 of which the content is incorporated herein by reference) (0.233 mol) in CH3ONa 30percent in CH3OH (222.32 ml) and CH3OH (776 ml) was stirred and refluxed overnight, then poured out on ice and extracted with CH2Cl2. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/cyclohexane 20/80 and then 100/0; 20-45 μm). The pure fractions were collected and the solvent was evaporated. Yield: 25 g of intermediate 9 (33 percent) .

Reference: [1] ChemMedChem, 2017, vol. 12, # 2, p. 106 - 119
[2] Tetrahedron, 2007, vol. 63, # 2, p. 451 - 460
[3] Chinese Chemical Letters, 2015, vol. 26, # 6, p. 790 - 792
[4] Patent: WO2005/70430, 2005, A1, . Location in patent: Page/Page column 34-35
[5] Patent: WO2006/67048, 2006, A1, . Location in patent: Page/Page column 27
[6] Patent: WO2004/11436, 2004, A1, . Location in patent: Page 18
[7] Patent: WO2005/70924, 2005, A1, . Location in patent: Page/Page column 27
[8] Patent: WO2007/435, 2007, A1, . Location in patent: Page/Page column 46
[9] Patent: WO2007/14934, 2007, A2, . Location in patent: Page/Page column 33
[10] Patent: WO2007/14940, 2007, A2, . Location in patent: Page/Page column 41
[11] Patent: WO2008/68266, 2008, A1, . Location in patent: Page/Page column 57
  • 3
  • [ 654655-80-8 ]
  • [ 654655-69-3 ]
  • [ 2752-87-6 ]
YieldReaction ConditionsOperation in experiment
91.8% With sodium hydroxide In tetrahydrofuran; water at 20℃; 0.1 kg of 1- (6-bromo-2-methoxy-3-quinolyl) -4- dimethylamino-2- (1-naphthyl) -1-phenyl-2-butanol was added to 2 L Tetrahydrofuran, 2L of water and 0.1kg of sodium hydroxide were added after stirring, the reaction was stirred at room temperature, the organic layer was separated,Toluene extract the aqueous layer, the combined organic phase, dried over anhydrous sodium sulfate, spin-dried,The crude mixture Compound A and Compound B were obtained.The resulting crude mixture was dissolved in ethyl acetate, hydrochloric acid was added and the organic layer was spin-dried to give 54.26 g of compound A,Yield 91.8percent, purity 98.2percent; The acid layer was made basic with potassium carbonate, extracted with toluene, the combined organic layer,Drying over anhydrous sodium sulfate gave 34.86 g of compound B, yield 85.2percent, purity 95.2percent.
Reference: [1] Patent: CN105198808, 2017, B, . Location in patent: Paragraph 0039; 0042; 0045; 0047-0049; 0051; 0054; 0057
  • 4
  • [ 654655-80-8 ]
  • [ 654655-69-3 ]
  • [ 10320-49-7 ]
Reference: [1] Chinese Chemical Letters, 2015, vol. 26, # 6, p. 790 - 792
  • 5
  • [ 654655-68-2 ]
  • [ 67-56-1 ]
  • [ 124-41-4 ]
  • [ 654655-69-3 ]
YieldReaction ConditionsOperation in experiment
89% for 8 h; Heating / reflux Preparation of 3 -Benzyl- 6-bromo-2-m ethoxy-q u m olin e; To a stirred solution of compound 3-Benzyl-6-bromo-2-chloro-qumolme (5 O g, 15 0 mmol) m dry methanol (50 ml) was added sodium methoxide (30percent w/v m methanol, 15.0 ml, 84 0 mmol) and the contents were heated under reflux for 8 h The volatiles were removed under reduced pressure, poured into ice-water mixture, the solid separated out was filtered, washed with water and dried to furnish the compound (4 4 g, 89percent) as an off-white solid, Mp 83-850C 1H NMR (400 MHz, CDCl3). δ 4.02 (s, 2 H), 4 07 (s, 3 H), 7 20-7 26 (m, 3 H), 7 29-7 34 (m, 2 H), 7 47 (s, 1 H), 7 60 (dd, J = 8 0, 4 0 Hz, 1 H), 7 60 (dd, J = 8 8, 2 2 Hz, 1 H), 7.73 (d, J= 2.0 Hz, 1 H) (M+H)+= 328, 330
33% Heating / reflux c. Preparation of intermediate 11; A mixture of intermediate 10 (0.233 mol) in CH3ONa(30 percent) in methanol (222.32 ml) and methanol (776 ml) was stirred and refluxed overnight, then poured out on ice and extracted with CH2Cl2 . The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated . The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/cyclohexane 20/80 and then 100/0; 20-45 μm). The pure fractions were collected and the solvent was evaporated . Yield: 25 g of intermediate 11 (33 percent) (melting point: 84°C).
33% Heating / reflux c) Preparation of intermediate 6; A mixture of intermediate 5 (0.233 mol) in CH3ONa 30 percent in CH3OH (222.32 ml) and CH3OH (776 ml) was stirred and refluxed overnight, then poured out on ice and extracted with CH2Cl2. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/cyclohexane 20/80 and then 100/0; 20-45 μm). The pure fractions were collected and the solvent was evaporated. Yield: 25 g of intermediate 6 (33 percent).
Reference: [1] Patent: WO2009/91324, 2009, A1, . Location in patent: Page/Page column 23
[2] Patent: WO2007/436, 2007, A1, . Location in patent: Page/Page column 33
[3] Patent: WO2007/14885, 2007, A1, . Location in patent: Page/Page column 31
  • 6
  • [ 106-40-1 ]
  • [ 654655-69-3 ]
Reference: [1] Chinese Chemical Letters, 2015, vol. 26, # 6, p. 790 - 792
[2] ChemMedChem, 2017, vol. 12, # 2, p. 106 - 119
  • 7
  • [ 316146-27-7 ]
  • [ 654655-69-3 ]
Reference: [1] Chinese Chemical Letters, 2015, vol. 26, # 6, p. 790 - 792
[2] ChemMedChem, 2017, vol. 12, # 2, p. 106 - 119
  • 8
  • [ 99455-05-7 ]
  • [ 654655-69-3 ]
Reference: [1] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 10, p. 1019 - 1024
  • 9
  • [ 924633-09-0 ]
  • [ 654655-69-3 ]
Reference: [1] Tetrahedron, 2007, vol. 63, # 2, p. 451 - 460
  • 10
  • [ 924658-20-8 ]
  • [ 654655-69-3 ]
Reference: [1] Tetrahedron, 2007, vol. 63, # 2, p. 451 - 460
  • 11
  • [ 37442-45-8 ]
  • [ 654655-69-3 ]
Reference: [1] Tetrahedron, 2007, vol. 63, # 2, p. 451 - 460
  • 12
  • [ 105479-98-9 ]
  • [ 654655-69-3 ]
Reference: [1] Tetrahedron, 2007, vol. 63, # 2, p. 451 - 460
  • 13
  • [ 100-39-0 ]
  • [ 654655-69-3 ]
Reference: [1] ACS Medicinal Chemistry Letters, 2017, vol. 8, # 10, p. 1019 - 1024
  • 14
  • [ 645-45-4 ]
  • [ 654655-69-3 ]
Reference: [1] ChemMedChem, 2017, vol. 12, # 2, p. 106 - 119
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