1-Cyclopropylmethyl-1H-pyrazole-4-boronic acid, pinacol ester

Cat.NO.:A200378 Purity:97%

Product Details of [ 1000801-75-1 ]

CAS No. :	1000801-75-1
Formula :	C₁₃H₂₁BN₂O₂
M.W :	248.13
SMILES Code :	CC1(C)C(C)(C)OB(C2=CN(CC3CC3)N=C2)O1
MDL No. :	MFCD15474887
InChI Key :	LJUAHBJQFILHLS-UHFFFAOYSA-N
Pubchem ID :	53407213

Safety of [ 1000801-75-1 ]

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

Computational Chemistry of [ 1000801-75-1 ] Show Less

Physicochemical Properties

Num. heavy atoms	18
Num. arom. heavy atoms	5
Fraction Csp3	0.77
Num. rotatable bonds	3
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	72.27
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	1.9
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.53
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.	1.14
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	1.13
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.14

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.58
Solubility	0.648 mg/ml ; 0.00261 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.	-2.28
Solubility	1.29 mg/ml ; 0.00519 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	-3.02
Solubility	0.238 mg/ml ; 0.000957 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	No
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	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.46 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<1.0
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)	3.14

Application In Synthesis of [ 1000801-75-1 ]

* 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.

Downstream synthetic route of [ 1000801-75-1 ]

[ 1000801-75-1 ] Synthesis Path-Downstream 1~3

1
[ 1000801-75-1 ]
[ 102169-44-8 ]
4-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-5-methylbenzene-1,2-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In propan-1-ol; water; at 120℃; for 2h;Inert atmosphere;	<strong>[102169-44-8]4-bromo-5-methylbenzene-1,2-diamine</strong> (400 mg, 1 .99 mmol), 1-(cyclopropylmethyl)-4-(4, 4,5,5-tetramethyl-1,3, 2-dioxaborolan-2-yl)-1H-pyrazole (see Intermediate 01-06; 543 mg, 2.19 mmol) and tetrakis(triphenylphosphine)palladium(0) (1 15 mg, 99.5 _) were added to an aq. solution of potassium carbonate (3.0 ml, 2.0 M, 6.0 mmol) and 1-propanol (8.2 ml). The mixture was stirred under an atmosphere of argon for 2h at 120C. The mixture was then concentrated under reduced pressure and purified by flash chromatography on silica gel to give 510 mg (59 % purity, 62 % yield) of the title compound. 1H-NMR (400MHz, DMSO-d6): _ [ppm]= 0.33 – 0.56 (m, 4H), 1 .18 – 1 .30 (m, 1H), 2.12 (s, 3H), 3.95 (d, 2H), 4.19 – 4.43 (m, 4H), 6.37 (s, 1H), 6.53 (s, 1H), 7.42 (d, 1H), 7.71 (d, 1H). LC-MS (Method 2): Rt = 0.93 min; MS (ESIpos): m/z = 243 [M+H]+

References: [1]Patent: WO2017/207534,2017,A1 .Location in patent: Page/Page column 182.

2
[ 1000801-75-1 ]
[ 102169-44-8 ]
4-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-5-fluorobenzene-1,2-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dichloro(1,1′-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In tetrahydrofuran; water; at 60℃;	4-bromo-5-fluorobenzene-1,2-diamine (500 mg, 2.44 mmol), 1-(cyclopropylmethyl)-4-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (see Intermediate 01-06; 1.21 g, 4.88 mmol), an aq. solution of sodium carbonate (3.0 ml, 2.0 M, 6.1 mmol) and 1 ,1 ‘-bis(diphenylphosphino)ferrocene-palladium(ll)dichloride dichloromethane complex (49.8 mg, 61.0 _) were stirred in THF (1 1 ml) overnight at 60C. The mixture was diluted with water and extracted three times with dichloromethane. The combined organic phases were dried over a silicone filter and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica gel to give 350 mg (90 % purity, 52 % yield) of the title compound. LC-MS (Method 2): Rt = 0.84 min; MS (ESIpos): m/z = 247 [M+H]+ 1H-NMR (400MHz, DMSO-d6): _ [ppm]= 0.32 – 0.39 (m, 2H), 0.49 – 0.56 (m, 2H), 1.24 (s, 1H), 3.96 (d, 2H), 4.26 – 4.38 (m, 2H), 4.76 (s, 2H), 6.35 (d, 1H), 6.71 (d, 1H), 7.57 (dd, 1H), 7.84 (dd, 1H).

References: [1]Patent: WO2017/207534,2017,A1 .Location in patent: Page/Page column 185-186.

3
[ 335349-57-0 ]
[ 1000801-75-1 ]
5-chloro-4-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-2-nitroaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 95℃; for 2.0h;	<strong>[335349-57-0]5-chloro-4-iodo-2-nitroaniline</strong> (see Intermediate 05-01 ; 500 mg, 1 .68 mmol), 1-(cyclopropylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole see Intermediate 01-06; 831 mg, 3.35 mmol), potassium phosphate (71 1 mg, 3.35 mmol) and tetrakis(triphenylphosphine)palladium(0) (96.8 mg, 83.8 _) were stirred in dioxane (15 ml) for 2h at 95C. The reaction mixture was diluted with water and extracted three times with dichloromethane. The combined organic phases were dried over a silicone filter and concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica gel to give 165 mg (87 % purity, 29 % yield) of the title compound. LC-MS (Method 2): Rt = 1 .1 1 min; MS (ESIpos): m/z = 293 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) _ [ppm]: 0.336 (0.58), 0.340 (0.49), 0.347 (0.52), 0.351 (0.55), 0.362 (0.64), 0.374 (1 .65), 0.378 (1 .38), 0.386 (1 .52), 0.389 (1 .60), 0.400 (0.72), 0.492 (0.52), 0.497 (0.53), 0.509 (0.88), 0.513 (0.67), 0.518 (1 .67), 0.523 (1.59), 0.528 (1 .02), 0.535 (0.77), 0.539 (1 .56), 0.544 (1 .49), 0.554 (0.55), 1.156 (4.73), 1.227 (0.40), 1 .232 (0.54), 1 .246 (16.00), 1 .265 (0.73), 1 .282 (0.41 ), 2.518 (0.89), 2.523 (0.69), 3.159 (0.51 ), 3.172 (0.46), 3.949 (1.13), 3.967 (1 .12), 3.981 (3.24), 3.999 (3.23), 7.212 (4.49), 7.492 (2.57), 7.565 (0.97), 7.732 (3.25), 7.734 (3.03), 7.940 (0.48), 7.958 (1 .06), 7.960 (1 .05), 8.063 (4.45), 8.1 19 (3.05), 8.121 (2.92).

References: [1]Patent: WO2017/207534,2017,A1 .Location in patent: Page/Page column 183-184.

Details

Reviews

There are no reviews yet.

Be the first to review “1-Cyclopropylmethyl-1H-pyrazole-4-boronic acid, pinacol ester”

Products