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[ CAS No. 1256387-87-7 ] {[proInfo.proName]}

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Chemical Structure| 1256387-87-7
Chemical Structure| 1256387-87-7
Structure of 1256387-87-7 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1256387-87-7 ]

CAS No. :1256387-87-7 MDL No. :MFCD28386938
Formula : C24H34BN3O4 Boiling Point : -
Linear Structure Formula :- InChI Key :MYPUONINDNZBTH-GMBSWORKSA-N
M.W : 439.36 Pubchem ID :67506198
Synonyms :

Calculated chemistry of [ 1256387-87-7 ]

Physicochemical Properties

Num. heavy atoms : 32
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.67
Num. rotatable bonds : 5
Num. H-bond acceptors : 5.0
Num. H-bond donors : 1.0
Molar Refractivity : 129.9
TPSA : 76.68 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.02 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 4.17
Log Po/w (WLOGP) : 3.62
Log Po/w (MLOGP) : 2.32
Log Po/w (SILICOS-IT) : 2.66
Consensus Log Po/w : 2.55

Druglikeness

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

Water Solubility

Log S (ESOL) : -5.07
Solubility : 0.00375 mg/ml ; 0.00000853 mol/l
Class : Moderately soluble
Log S (Ali) : -5.49
Solubility : 0.00143 mg/ml ; 0.00000325 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -5.6
Solubility : 0.0011 mg/ml ; 0.00000251 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 5.61

Safety of [ 1256387-87-7 ]

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 [ 1256387-87-7 ]

* 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 [ 1256387-87-7 ]
  • Downstream synthetic route of [ 1256387-87-7 ]

[ 1256387-87-7 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 1256387-74-2 ]
  • [ 99770-93-1 ]
  • [ 1256387-87-7 ]
YieldReaction ConditionsOperation in experiment
85% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,2-dimethoxyethane; water at 90℃; for 4 h; Inert atmosphere I. Preparation of Compound 613. A mixture of 3-(6-Bromo-1 H-benzoimidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2- carboxylic acid ferf-butyl ester 618 (264 mg, 0.673 mmol), benzene-1 ,4-diboronic acid dipinocal ester (5 eq., 3.36 g, 6.95 mmol), tetrakis(triphenylphosphine)palladium (5percent, 39 mg) and 2M potassium carbonate aqueous solution (3 eq., 1.01 ml_) in 5 mL DME was heated to 90°C under Ar for 4 hours. The reaction mixture was cooled and diluted in ethyl acetate and washed with saturated sodium bicarbonate solution. The organic layer dried (MgS04), concentrated and purified by flash column chromatography (silica gel, 20 to 60percent ethyl acetate/hexane) to give 3-{6-[4-(4,4,5,5-Tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-phenyl]-1 H-benzoimidazol-2-yl}-2- aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester 613 (295 mg, yield 85percent). LCMS- ESI": calc'd for C3oH38BN304: 515.45; Found: 516.1 (M+H+).
85% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,2-dimethoxyethane; water at 90℃; for 4 h; Inert atmosphere I.
Preparation of Compound 613
A mixture of 3-(6-Bromo-1H-benzoimidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester 618 (264 mg, 0.673 mmol), benzene-1,4-diboronic acid dipinocal ester (5 eq., 3.36 g, 6.95 mmol), tetrakis(triphenylphosphine)palladium (5percent, 39 mg) and 2M potassium carbonate aqueous solution (3 eq., 1.01 mL) in 5 mL DME was heated to 90° C. under Ar for 4 hours.
The reaction mixture was cooled and diluted in ethyl acetate and washed with saturated sodium bicarbonate solution.
The organic layer dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 60percent ethyl acetate/hexane) to give 3-{6-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-benzoimidazol-2-yl}-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester 613 (295 mg, yield 85percent). LCMS-ES1-: calc'd for C30H38BN3O4: 515.45. Found: 516.1 (M+H+).
Reference: [1] Patent: WO2013/40492, 2013, A2, . Location in patent: Page/Page column 91-92
[2] Patent: US2013/273005, 2013, A1, . Location in patent: Paragraph 0350
  • 2
  • [ 1256387-74-2 ]
  • [ 73183-34-3 ]
  • [ 1256387-87-7 ]
YieldReaction ConditionsOperation in experiment
1.16 g With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate In 1,4-dioxane at 95℃; for 3.5 h; Inert atmosphere 1.08 g of compound 12, [1,1'-bis (diphenylphosphino) ferrocene] dichlorophenyl dichloromethane complex 114 mg,Fumarate borate 1.53 g,Potassium acetate 700mg,In the nitrogen under the protection of the reaction unit with a condensing device,Add 30 mL of boiled deoxygenated dioxane with stirring.Above the suspension of nitrogen protection in the 95 oil bath stir in the antiShould be 3.5 hours. Drying the reaction solution,Column chromatography (petroleum ether / ethyl acetate, 10: 1, 2: 1) gave product 13 as an off-white solid (1.16 g).
26 g With dichlorobis(p-dimethylaminophenyldi-tert-butylphosphine)palladium; potassium acetate In 1,4-dioxane at 80 - 85℃; (1R,3S,4S)-3-(6-bromo-1H-benzimidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylic acid 1,1-dimethylethyl ester (25 g) was suspended in 1,4 dioxane (250 ml), followed by addition of bis(pinacolate) diboron (35.5 g), dichlorobis(di-tert- butylphenylphosphine)palladium(II) catalyst (1.5 g) and potassium acetate (18 g) at room temperature and allow to raise the temperature 80-85°C for 2-3 hours till it complies the reaction. The reaction completion is confirm by TLC, the solvent (1, 4 dioxane) was distilled out under reduced pressure and the reaction mass was cooled to room temperature by adding purified water and dichloromethane, to separate the layers. The organic layer was distilled out under reduced pressure to get a residue and further it is treated with cyclohexane to get a solid. Finally, the resultant solid was filtered and dried over at 40- 50°C to obtain a titled compound (26 g).
Reference: [1] Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 2033 - 2046
[2] Patent: CN106117187, 2016, A, . Location in patent: Paragraph 0071; 0072; 0073
[3] Patent: CN106608870, 2017, A, . Location in patent: Paragraph 0033; 0050-0051
[4] Patent: WO2017/72596, 2017, A1, . Location in patent: Page/Page column 13; 14
[5] Patent: CN107954990, 2018, A, . Location in patent: Paragraph 0127; 0129; 0131; 0200; 0270
  • 3
  • [ 1256387-73-1 ]
  • [ 1256387-87-7 ]
Reference: [1] Patent: US2013/273005, 2013, A1,
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 2033 - 2046
[3] Patent: WO2013/40492, 2013, A2,
  • 4
  • [ 1575-37-7 ]
  • [ 1256387-87-7 ]
Reference: [1] Patent: US2013/273005, 2013, A1,
[2] Patent: CN106117187, 2016, A,
[3] Patent: WO2013/40492, 2013, A2,
  • 5
  • [ 1181573-36-3 ]
  • [ 1256387-87-7 ]
Reference: [1] Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 2033 - 2046
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