1-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Cat.NO.:A262241 Purity:97%

Product Details of [ 1002334-12-4 ]

CAS No. :	1002334-12-4
Formula :	C₁₅H₁₉BN₂O₂
M.W :	270.13
SMILES Code :	CC1(C)C(C)(C)OB(C2=CN(C3=CC=CC=C3)N=C2)O1
MDL No. :	MFCD12400941
InChI Key :	XPAJFLOIPDXRRD-UHFFFAOYSA-N
Pubchem ID :	56965771

Safety of [ 1002334-12-4 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 1002334-12-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	20
Num. arom. heavy atoms	11
Fraction Csp3	0.4
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	80.04
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	36.28 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.0
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.88
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.17
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	1.67
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	1.38
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.62

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.6
Solubility	0.0672 mg/ml ; 0.000249 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.3
Solubility	0.135 mg/ml ; 0.000499 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-4.53
Solubility	0.00805 mg/ml ; 0.0000298 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	Yes
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	Yes
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	Yes
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.9 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<0.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12’782’590 molecules and tested on 40 external molecules (r² = 0.94)	2.84

Application In Synthesis of [ 1002334-12-4 ]

* 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 [ 1002334-12-4 ]
Downstream synthetic route of [ 1002334-12-4 ]

[ 1002334-12-4 ] Synthesis Path-Upstream 1~7

1
[ 15115-52-3 ]
[ 73183-34-3 ]
[ 1002334-12-4 ]

Yield	Reaction Conditions	Operation in experiment
50%	With potassium acetate In dimethyl sulfoxide at 20 – 80℃;	To a solution of compound 4-bromo-l -phenyl- lH-pyrazo Ie (0.5 g, 2.3 mmol) in DMSO (50 mL) was added KOAc (0.66 g, 6.8 mmol), bis(pinacolato)diboron (0.63 g, 2.5 mmol) and .yen.dCb(dpp{) (0.076g, 0.11 mmol) at room temperature. The reaction mixture was stirred overnight at 😯⁰C. The result mixture was diluted with EA, washed with brine, dried over Na₂SO₄, concentrated, purified by chromatography (EA:PE=1: 12) to give l-phenyl-4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-lH- pyrazole (0.3 g, 50percent) as light yellow solid

References:

[1] Patent: WO2009/155527, 2009, A2, . Location in patent: Page/Page column 134.

2
[ 23889-85-2 ]
[ 73183-34-3 ]
[ 1002334-12-4 ]

Yield	Reaction Conditions	Operation in experiment
48.15%	With (1,1′-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In dimethyl sulfoxide at 80℃; for 8 h; Inert atmosphere	A mixture of 4-iodo-1-phenyl-1H-pyrazole (706 mg, 2.59 mmol) , potassium acetate (762 mg, 7.76 mmol) , bis (pinacolato) diboron (860 mg, 3.37 mmol) and Pd (dppf) Cl₂(212 mg, 0.26 mmol) was suspended in DMSO (15 mL) . The system was exchanged with N₂. The mixture was stirred at 80 for 8 h. The reaction mixture was diluted with water (60 mL) . The resulting mixture was extracted with DCM (50 mL × 3) . The combined organic layers were washed with saturated aqueous NaCl (15 mL) , dried over anhydrous Na₂SO₄and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with PE/EtOAc (v/v) 20/1 to give a yellow solid product (340 mg, 48.15) .[1650]MS (ESI, pos. ion) m/z: 271.05 [M+1]⁺.

References:

[1] Patent: WO2016/615, 2016, A1, . Location in patent: Paragraph 00690.

3
[ 76-09-5 ]
[ 100-63-0 ]
[ 1002334-12-4 ]

References:

[1] Patent: CN105440067, 2016, A, . Location in patent: Paragraph 0018.

4
[ 508191-77-3 ]
[ 347389-74-6 ]
[ 1002334-13-5 ]
[ 1002334-12-4 ]

References:

[1] Journal of the American Chemical Society, 2009, vol. 131, p. 7762 – 7769.

[2] Angewandte Chemie – International Edition, 2007, vol. 46, # 45, p. 8656 – 8658.

[3] Journal of the American Chemical Society, 2009, vol. 131, p. 7762 – 7769.

5
[ 347389-74-6 ]
[ 1002334-13-5 ]
[ 1002334-12-4 ]

References:

[1] Angewandte Chemie – International Edition, 2007, vol. 46, # 45, p. 8656 – 8658.

6
[ 98-80-6 ]
[ 1002334-12-4 ]

References:

[1] Patent: WO2016/615, 2016, A1, .

7
[ 1002334-12-4 ]
[ 1201643-70-0 ]

Yield	Reaction Conditions	Operation in experiment
89%	With sodium periodate; ammonium acetate In water; acetone at 20℃;	To the solution of 4-pinacolatoboron- 1 H-pyrazole (0.6 g, 3.1 mmol) in acetone/water (30 mL, v/v=l: l) was added NaIO₄ (2.0 g, 9.3 mmol) and NH₄OAc (0.54 g, 7.1 mmol). The reaction mixture was stirred overnight at room temperature. The result mixture was concentrated to give residues, purification by chromatography (MeOH:DCM=l :5) to give compound lH-pyrazol-4- ylboronic acid (0.3 g, 89percent) as light yellow solid. MS (m/z) (IVf +H): 189.

References:

[1] Patent: WO2009/155527, 2009, A2, . Location in patent: Page/Page column 134-135.

Yield	Reaction Conditions	Operation in experiment
89%	With sodium periodate; ammonium acetate; In water; acetone; at 20℃;	To the solution of 4-pinacolatoboron- 1 H-pyrazole (0.6 g, 3.1 mmol) in acetone/water (30 mL, v/v=l: l) was added NaIO4 (2.0 g, 9.3 mmol) and NH4OAc (0.54 g, 7.1 mmol). The reaction mixture was stirred overnight at room temperature. The result mixture was concentrated to give residues, purification by chromatography (MeOH:DCM=l :5) to give compound lH-pyrazol-4- ylboronic acid (0.3 g, 89percent) as light yellow solid. MS (m/z) (IVf +H): 189.

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