5-Methyl-3-phenyl-1H-pyrazole | Pyrazoles

CAS No. :	3347-62-4
Formula :	C₁₀H₁₀N₂
M.W :	158.20
SMILES Code :	CC1=NNC(C2=CC=CC=C2)=C1
MDL No. :	MFCD00022385
InChI Key :	QHRSESMSOJZMCO-UHFFFAOYSA-N
Pubchem ID :	18774

Safety of [ 3347-62-4 ]

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

Computational Chemistry of [ 3347-62-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	11
Fraction Csp3	0.1
Num. rotatable bonds	1
Num. H-bond acceptors	1.0
Num. H-bond donors	1.0
Molar Refractivity	48.99
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	28.68 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.57
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	2.28
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.39
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.	1.77
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	3.06
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.21

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.87
Solubility	0.214 mg/ml ; 0.00135 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.	-2.52
Solubility	0.478 mg/ml ; 0.00302 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	-4.13
Solubility	0.0118 mg/ml ; 0.0000748 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	No
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	Yes
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.	-5.65 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	1.0
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	0.0 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)	1.77

Application In Synthesis of [ 3347-62-4 ]

* 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.

Downstream synthetic route of [ 3347-62-4 ]

[ 3347-62-4 ] Synthesis Path-Downstream 1~54

1
[ 110-91-8 ]
[ 79815-53-5 ]
[ 79815-71-7 ]
[ 3347-62-4 ]

References: [1]Journal of Organic Chemistry,1982,vol. 47,p. 295 - 300.

2
[ 77202-05-2 ]
[ 77202-10-9 ]
[ 3347-62-4 ]

References: [1]Chemical and Pharmaceutical Bulletin,1990,vol. 38,p. 1524 - 1526.
[2]Chemical and pharmaceutical bulletin,1988,vol. 36,p. 3838 - 3848.

3
[ 75-03-6 ]
[ 3347-62-4 ]
[ 851427-81-1 ]
1-ethyl-3-methyl-5-phenyl-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
123 mg; 56 mg	With sodium hydroxide; In acetonitrile; at 20℃; for 2h;	General procedure: A mixture of (E)-4-phenylbut-3-en-2-one (1e) (146 mg, 1.0 mmol) and TsNHNH2 (205 mg, 1.1 mmol) in CH3CN (2 mL) were stirred at room temperature for 3 h and then CH3CN (2 mL), NaOH (44 mg, 1.1 mmol) were added and the mixture was heated at reflux for 17 h, then NaOH (60 mg, 1.5 mmol) and benzyl bromide (255 mg, 1.5 mmol) were subsequently added and the mixture was stirred at room temperature for 2 h. The product was extracted with Et2O and the organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. Purification by chromatography on silica gel afforded the desired product 4s as white crystalline solid (194 mg, 78% yield).

References: [1]Tetrahedron,2005,vol. 61,p. 12377 - 12385.
[2]Tetrahedron,2013,vol. 69,p. 1427 - 1433.

4
[ 629-27-6 ]
[ 3347-62-4 ]
[ 851427-87-7 ]
3-methyl-1-octyl-5-phenyl-1H-pyrazole [ No CAS ]

References: [1]Tetrahedron,2005,vol. 61,p. 12377 - 12385.

5
[ 111-83-1 ]
[ 3347-62-4 ]
[ 851427-87-7 ]
3-methyl-1-octyl-5-phenyl-1H-pyrazole [ No CAS ]

References: [1]Tetrahedron,2005,vol. 61,p. 12377 - 12385.

6
[ 107-06-2 ]
[ 3347-62-4 ]
1-(2-chloroethyl)-5-methyl-3-phenylpyrazole [ No CAS ]
1-(2-chloroethyl)-3-methyl-5-phenylpyrazole [ No CAS ]

References: [1]Heterocycles,2005,vol. 65,p. 1691 - 1704.

7
[ 106-93-4 ]
[ 3347-62-4 ]
1-(2-bromoethyl)-5-methyl-3-phenylpyrazole [ No CAS ]
1-(2-bromoethyl)-3-methyl-5-phenylpyrazole [ No CAS ]
1,2-bis(5-methyl-3-phenylpyrazol-1-yl)ethane [ No CAS ]

References: [1]Heterocycles,2005,vol. 65,p. 1691 - 1704.

8
[ 3347-62-4 ]
[ 13808-66-7 ]

Yield	Reaction Conditions	Operation in experiment
	With bromine; In dichloromethane; at 0 - 20℃; for 2.5h;	To a solution of 5-methyl-3-phenyl-lH-pyrazole (8.0 g, 50.6 mmol) in dichloromethane(150 mL) was added bromine (8.08 g, 50.6 mmol) dropwise at 0 0C. The reaction was stirred at that temperature for 30 min and continued at room temperature for 2 h. After the reaction was quenched with an aqueous solution OfNa2SO3 (10% w/w, 10 mL), the organic solvent was removed and the aqueous mixture was extracted with EtOAc, washed with brine, dried over MgSO4, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a yellow oil (9.5 g). LCMS mlz = 236.9 (M+H4). 1H NMR (400 MHz, DMSO-J6) delta ppm 2.26 (s, 3H), 7.30-7.57 (m, 5H), 13.12 (s, IH).

References: [1]Tetrahedron,2007,vol. 63,p. 8104 - 8111.
[2]Synthesis,1982,p. 844 - 846.
[3]Patent: WO2010/68242,2010,A1 .Location in patent: Page/Page column 124.
[4]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3716 - 3722.

9
[ 3347-62-4 ]
[ 863494-35-3 ]

References: [1]Heterocycles,2005,vol. 65,p. 1691 - 1704.

10
[ 3347-62-4 ]
1-(2-diphenylphosphanyl-phenyl)-5-methyl-3-phenyl-1<i>H</i>-pyrazole [ No CAS ]

References: [1]Tetrahedron Letters,2004,vol. 45,p. 9525 - 9528.

11
acetophenone (3-imino-1-methyl-3-phenylprop-1-enyl)hydrazone [ No CAS ]
[ 3347-62-4 ]

References: [1]Journal of Chemical Research, Miniprint,1985,p. 1478 - 1492.

12
[ 94012-44-9 ]
[ 3347-62-4 ]

References: [1]Bulletin of the Chemical Society of Japan,1984,vol. 57,p. 2954 - 2956.

13
[ 98-86-2 ]
phenylacetaldehyde ; benzaldehyde [ No CAS ]
[ 3347-62-4 ]

References: [1]Bulletin of the Chemical Society of Japan,1984,vol. 57,p. 2954 - 2956.

14
[ 100-47-0 ]
3-phenyl-1,2-benzisoselenazole [ No CAS ]
[ 3347-62-4 ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1984,p. 611 - 614.

15
[ 3347-62-4 ]
[ 92670-83-2 ]

References: [1]Journal of Organic Chemistry,1984,vol. 49,p. 4647 - 4656.

16
[ 3347-62-4 ]
[ 84691-24-7 ]

References: [1]Synthesis,1982,p. 844 - 846.

17
[ 3347-62-4 ]
[ 84691-25-8 ]

References: [1]Synthesis,1982,p. 844 - 846.

18
4,4-dimethyl-2,2-dioxo-2λ'-[1,2,3] oxathiazinane-3-carboxylic acid tert-butyl ester [ No CAS ]
[ 865-47-4 ]
[ 3347-62-4 ]
[ 93-91-4 ]
[ 521267-14-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; hydrazine; In dichloromethane; N,N-dimethyl-formamide; acetonitrile;	Step C]: [1,1-Dimethyl-3-(5-methyl-3-phenyl-pyrazol-1-yl)-propyl]-carbamic Acid Tert-Butyl Ester 5-Methyl-3-phenyl-1H-pyrazole (320 mg, prepared from benzoylacetone and hydrazine according to Ali et al., Pak. J. Sci. Ind. Res. 1993, 36 (12), 502) was dissolved in DMF (7 ml) and cooled to 0 C. with an ice bath. Potassium-tert-butoxide (284 mg) was added in portions and the mixture was stirred for 45 min at 0 C. Then, 4,4-dimethyl-2,2-dioxo-2lambda'-[1,2,3]oxathiazinane-3-carboxylic acid tert-butyl ester (617 mg) was added in one portion and the reaction mixture was allowed to stir for 20 hours at RT. HCl (1N aqueous solution, 10 ml) was added and stirring was continued for 15 minutes. The mixture was diluted with ether, washed with water and brine (the aqueous layers were re-extracted twice with ether), dried and evaporated. The crude product was purified by flash chromatography (0 to 15% gradient of CH3CN in CH2Cl2) to give the desired product as a yellow gum. Yield: 545 mg. A regioisomer present in minor amounts was removed in the chromatographic purification step. MS (ISP): 344.5 (MH+)

References: [1]Patent: US2003/130281,2003,A1 .

19
sulfimidate [ No CAS ]
[ 3347-62-4 ]
[ 207557-35-5 ]
(2S)-1-[(1S)-1-Methyl-2-(5-methyl-3-phenyl-pyrazol-1-yl)-ethylamino]-acetyl}-pyrrolidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 112 (2S)-1-[(1S)-1-Methyl-2-(5-methyl-3-phenyl-pyrazol-1-yl)-ethylamino]-acetyl}-pyrrolidine-2-carbonitrile The title compound was obtained in analogy to example 78, steps C] to E] from <strong>[3347-62-4]5-methyl-3-phenyl-1H-pyrazole</strong> by replacing sulfimidate XIX with IV and with the exception, that the final coupling step with IIA was done as described in example 1. The title compound was obtained as the free amine as a glass. MS (ISP): 352.4 (MH+).

References: [1]Patent: US2003/130281,2003,A1 .

20
[ 96-09-3 ]
[ 3347-62-4 ]
[ 742097-02-5 ]

References: [1]Polish Journal of Chemistry,2007,vol. 81,p. 1987 - 1999.

21
[ 20780-53-4 ]
[ 3347-62-4 ]
[ 1073427-17-4 ]
C₁₈H₁₈N₂O [ No CAS ]
2-(5-methyl-3-phenyl-pyrazol-1-yl)-2-phenyl-ethanol [ No CAS ]

References: [1]Polish Journal of Chemistry,2007,vol. 81,p. 1987 - 1999.

22
[ 3347-62-4 ]
[ 263260-09-9 ]
(4S,5S)-4-(3-phenyl-5-methylpyrazol-1-ylmethyl)-5-(4-methylsulfanyl-phenyl)-2-phenyl-4,5-dihydrooxazole [ No CAS ]

References: [1]Polish Journal of Chemistry,2007,vol. 81,p. 1987 - 1999.

23
[ 3347-62-4 ]
(4S)-2-chloromethyl-4-ethyl-2-oxazoline [ No CAS ]
C₁₆H₂₁N₃O₂ [ No CAS ]

References: [1]Polish Journal of Chemistry,2007,vol. 81,p. 1987 - 1999.

24
[ 16940-66-2 ]
[ 49633-25-2 ]
[ 3347-62-4 ]
Na⁽¹⁺⁾*(HB((C₆H₅)(CH₃)C₃HN₂)2((CH₃)2CHC₃H₂N₂))^(1-)=Na(HB((CH₃)(C₆H₅)C₃HN₂)2)((CH₃)2CHC₃H₂N₂) [ No CAS ]

References: [1]European Journal of Inorganic Chemistry,2003,p. 89 - 93.

25
pentacarbonyl(1-ethoxy-3-phenylpropyn-1-ylidene)tungsten [ No CAS ]
[ 3347-62-4 ]
[(CO)5W(C(OC₂H₅)CHC(C₆H₅C₃HN₂CH₃)C₆H₅)] [ No CAS ]

References: [1]Journal of Organometallic Chemistry,2006,vol. 691,p. 1984 - 1992.

26
potassium borohydride [ No CAS ]
thallium(I) nitrate [ No CAS ]
[ 3347-62-4 ]
thallium hydrotris(3-phenyl-5-methylpyrazol-1-yl)borate [ No CAS ]

References: [1]Inorganic Chemistry,1994,vol. 33,p. 3666 - 3676.

27
potassium borohydride [ No CAS ]
[ 3347-62-4 ]
potassium hydrotris(3-phenyl-5-methyl-pyrazol-1-yl)borate [ No CAS ]

References: [1]Inorganica Chimica Acta,2002,vol. 337,p. 459 - 462.

28
chloro(1,5-cyclooctadiene)iridium(I) dimer [ No CAS ]
[ 3347-62-4 ]
bis(cycloocta-1,5-diene)bis(μ-3-phenyl-5-methylpyrazolyl)diiridium(I) [ No CAS ]

References: [1]Organometallics,1985,vol. 4,p. 1107 - 1114.

29
potassium borohydride [ No CAS ]
[ 3347-62-4 ]
[ 51581-48-7 ]
K pyrazolylbis(1-(o-anisyl)-2-thioimidazolyl)borate [ No CAS ]

References: [1]Chemical Communications,2001,p. 1026 - 1027.

30
[ 16940-66-2 ]
[ 3347-62-4 ]
sodium [hydrotris(3-phenyl-5-methylpyrazolyl)borate] [ No CAS ]
sodium hydrogen bis(5-methyl-3-phenylpyrazol-1-yl) (3-methyl-5-phenylpyrazol-1-yl) borate [ No CAS ]

References: [1]Polyhedron,2001,vol. 20,p. 237 - 244.
[2]Polyhedron,2001,vol. 20,p. 237 - 244.

31
[ 67-51-6 ]
[ 16940-66-2 ]
[ 3347-62-4 ]
sodium [hydrotris(3-phenyl-5-methylpyrazolyl)borate] [ No CAS ]
sodium hydrogen bis(5-methyl-3-phenylpyrazol-1-yl) (3-methyl-5-phenylpyrazol-1-yl) borate [ No CAS ]
sodium [hydrobis(3-methyl-5-phenylpyrazolyl)(3-phenyl-5-methylpyrazolyl)borate] [ No CAS ]

References: [1]Polyhedron,2001,vol. 20,p. 2551 - 2558.

32
[ 16940-66-2 ]
[ 56426-41-6 ]
[ 3347-62-4 ]
sodium [hydrotris(3-phenyl-5-methylpyrazolyl)borate] [ No CAS ]

References: [1]Polyhedron,2002,vol. 21,p. 2743 - 2753.

33
N,N-dimethyl-(S)-1-[(R)-2-(diphenylphosphino)ferrocenyl]ethylamine [ No CAS ]
[ 3347-62-4 ]
1-((S)-1-[(R)-2-(diphenylphosphino)ferrocenyl]ethyl)-5-methyl-3-phenyl-1H-pyrazole [ No CAS ]

References: [1]Organometallics,1995,vol. 14,p. 5415 - 5425.

34
[(norbornadiene)RhCl]2 [ No CAS ]
[ 3347-62-4 ]
[ 167287-02-7 ]

References: [1]Polyhedron,1995,vol. 14,p. 1139 - 1148.

35
zinc(II) perchlorate [ No CAS ]
[ 3347-62-4 ]
[ 60-24-2 ]
[(2-thiolateethanolate)bis(5-methyl-3-phenyl-pyrazolate)dizinc(II)]6 [ No CAS ]

References: [1]Chemical Communications,2003,p. 1278 - 1279.

36
[ 109-99-9 ]
[ 39929-21-0 ]
[ 3347-62-4 ]
[Au(μ-3-Me-5-Ph-pz)]3*THF [ No CAS ]

References: [1]Inorganic Chemistry,2003,vol. 42,p. 261 - 263.

37
[ 2817-73-4 ]
[ 16940-66-2 ]
[ 3347-62-4 ]
[ 503156-57-8 ]