60481-51-8|(3,4-Dimethylphenyl)hydrazine hydrochloride| Ambeed

Structure of 60481-51-8

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Quality Control of [ 60481-51-8 ] Purity: 97% SDS Specification

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Product Details of [ 60481-51-8 ]

CAS No. :	60481-51-8
Formula :	C₈H₁₃ClN₂
M.W :	172.66
SMILES Code :	[H+].C1=C(NN)C=C(C(=C1)C)C.[Cl-]
MDL No. :	MFCD00052270
Boiling Point :	No data available
InChI Key :	YYMIOVAEQIEPET-UHFFFAOYSA-N
Pubchem ID :	173740

Safety of [ 60481-51-8 ]

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

Computational Chemistry of [ 60481-51-8 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.25
Num. rotatable bonds	1
Num. H-bond acceptors	1.0
Num. H-bond donors	2.0
Molar Refractivity	49.43
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	38.05 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	2.56
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	-1.49
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.	2.34
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	1.25
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.93

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.86
Solubility	0.238 mg/ml ; 0.00138 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.	-3.01
Solubility	0.17 mg/ml ; 0.000985 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	-2.83
Solubility	0.254 mg/ml ; 0.00147 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	Low
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
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	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.	-5.54 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.	0.56

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)	1.34

Application In Synthesis of [ 60481-51-8 ]

* 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 [ 60481-51-8 ]

[ 60481-51-8 ] Synthesis Path-Downstream 1~35

1
[ 583-71-1 ]
[ 60481-51-8 ]
[ 4920-95-0 ]

References: [1]Bulletin of the Chemical Society of Japan,1983,vol. 56,p. 1113 - 1115.

2
[ 60481-51-8 ]
3-[3-(2-chlorophenyl)-5-methyl-4-isoxazolylcarbonylamino]-5,6-dimethyl-2-phenyl-1H-indole [ No CAS ]

References: [1]Chemistry of Heterocyclic Compounds,2003,vol. 39,p. 161 - 167.

3
[ 60481-51-8 ]
3-[3-(2-chlorophenyl)-5-methyl-4-isoxazolylcarbonylamino]-4,5-dimethyl-2-phenyl-1H-indole [ No CAS ]

References: [1]Chemistry of Heterocyclic Compounds,2003,vol. 39,p. 161 - 167.

4
[ 60481-51-8 ]
[ 374924-93-3 ]

References: [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 3730 - 3745.

5
[ 60481-51-8 ]
4-{<i>N</i>'-[1-(3,4-dimethyl-phenyl)-5-oxo-1,5-dihydro-pyrazol-4-ylidene]-hydrazino}-3-hydroxy-naphthalene-1-sulfonic acid [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 3730 - 3745.

6
[ 141-97-9 ]
[ 60481-51-8 ]
[ 277299-70-4 ]

Yield	Reaction Conditions	Operation in experiment
76%	With sodium bicarbonate; sodium acetate; In diethyl ether; acetic acid;	f 1-(3,4-Dimethylphenyl)-3-methyl-3-pyrazolin-5-one A solution of <strong>[60481-51-8]3,4-dimethylphenylhydrazine hydrochloride</strong> (17.7 g; 0.1 mol.), ethyl acetoacetate (13.0 g; 0.1 mol.) and sodium acetate (8.2 g; 0.1 mol.) in glacial acetic acid (250 mL) was stirred and heated under reflux for 24 h. The mixture was cooled and evaporated and the residue dissolved in diethyl ether (IL) and carefully washed with sat. aqu. sodium hydrogen carbonate (5*200 mL). The ethereal layer was evaporated to afford the title compound (15.4 g; 76percent). 1H NMR (300 MHz, d6-DMSO) delta11.30 (br s, 1H), 7.49 (d, J=1.4 Hz, 1H), 7.43 (dd, J=8.2 Hz, 1H), 7.14 (d, J=8.2 Hz, 1H), 5.31 (s, 1H), 2.20 (s, 3H), 2.22 (s, 3H), 2.08 (s, 3H); MS(ES) m/z 203 [M+H].
76%	With sodium acetate; In acetic acid; for 24h;Heating / reflux;	A solution of <strong>[60481-51-8]3,4-dimethylphenylhydrazine hydrochloride</strong> (17.7 g; 0.1 mol.), ethyl acetoacetate (13.0 g; 0.1 mol.) and sodium acetate (8.2 g; 0.1 mol.) in glacial acetic acid; (250 mL) was stirred and heated under reflux for 24 h. [0378] The mixture was cooled and evaporated and the residue dissolved in diethyl ether (1L) and carefully washed with sat. aqu. sodium hydrogen carbonate (5.x.200 mL). The ethereal layer was evaporated to afford the title compound (15.4 g; 76percent). 1H NMR (300 MHz, d6-DMSO) delta 11.30 (br s, 1H), 7.49 (d, J=1.4 Hz, 1H), 7.43 (dd, J=8.2 Hz, 1H), 7.14 (d, J=8.2 Hz, 1H), 5.31 (s, 1H), 2.20 (s, 3H), 2.22 (s, 3H), 2.08 (s, 3H); MS(ES) m/z 203 [M+H].
76%	With sodium acetate; acetic acid; for 24h;Reflux;	A solution of <strong>[60481-51-8]3,4-dimethylphenylhydrazine hydrochloride</strong> (17.7 g; 0.1 mol.), ethyl acetoacetate (13.0 g; 0.1 mol.) and sodium acetate (8.2 g; 0.1 mol.) in glacial acetic acid; (250 mL) was stirred and heated under reflux for 24h. The mixture was cooled and evaporated and the residue dissolved in diethyl ether (1L) and carefully washed with saturated aqueous sodium hydrogen carbonate (5 x 200 mL). The ethereal layer was evaporated to afford the title compound (15.4 g; 76percent).

References: [1]Patent: US2004/53299,2004,A1 .
[2]Patent: US2004/19190,2004,A1 .Location in patent: Page 17.
[3]Patent: WO2016/35018,2016,A1 .Location in patent: Page/Page column 13.

7
[ 87-13-8 ]
[ 60481-51-8 ]
[ 376593-74-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In ethanol; for 3h;Heating / reflux;	A suspension of <strong>[60481-51-8]3,4-dimethylphenylhydrazine hydrochloride</strong> (2.0 g; 0.012 mol.) and potassium carbonate (3.2 g; 0.023 mol.) in anhydrous ethanol (40.0 mL) was treated dropwise with diethyl(ethoxymethylene)malonate (2.5 g; 0.012 mol.) and the mixture stirred and heated under reflux for 3 h. After cooling the mixture was evaporated and the residue suspended in water and acid;ified to pH 2 followed by extraction with ethyl acetate. After drying and evaporation the resulting intermediate 1-(3,4-dimethyl-phenyl)-3-oxo-2,3-dihydro-1H-pyrazole-4-carboxylic acid; ethyl ester was dissolved in methanol (10.0 mL) and 10percent aqueous sodium hydroxide (10.0 mL) and stirred at room temperature for 3 h and then heated under reflux to effect hydrolysis. The solution was cooled and acid;ified to pH 4 with 3M aqu. hydrochloric acid; and stirred at room temperature for 2 h to effect decarboxylation. The mixture was extracted with ethyl acetate, dried and evaporated to give the title compound (87percent) as a yellow solid. 1H NMR (300 MHz, CDCl3) delta 7.61 (d, J=2.3 Hz, 1H), 7.55 (dd, J=8.2 and 2.3 Hz, 1H), 7.48 (t, J=1.3 Hz, 1H), 1.16 (d, J=8.2 Hz, 1H), 3.50 (d, J=1.3 Hz, 2H)

References: [1]Patent: US2004/19190,2004,A1 .Location in patent: Page 44.

8
4-dimethylaminocyclohexanone hydrochloride [ No CAS ]
[ 60481-51-8 ]
[ 60481-52-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In methanol; ethanol; hexane;	EXAMPLE 242 3-(Dimethylamino)-6,7-dimethyl-1,2,3,4-tetrahydrocarbazole A solution of 11.5 g. of 4-dimethylaminocyclohexanone hydrochloride and 11 g. of <strong>[60481-51-8]3,4-dimethylphenylhydrazine hydrochloride</strong> in 200 ml. of absolute ethyl alcohol was heated under reflux for 6 hours, cooled, filtered, and the filtrate was diluted with ether. The oily precipitate, which was collected by decantation and solidified on standing, was suspended in boiling isopropyl alcohol, filtered and dissolved in methyl alcohol. This solution was diluted with isopropyl alcohol and the methyl alcohol was removed by distillation. The cooled mixture was filtered to give 9.2 g. of a solid which was suspended in ether and treated with dilute potassium hydroxide. The ether extract was evaporated to dryness and the residue was suspended and boiled in hexane and filtered to give 3.2 g. of 3-(dimethylamino)-6,7-dimethyl-1,2,3,4-tetrahydrocarbazole, m.p. 183°-187°C.
	With potassium hydroxide; In methanol; ethanol; hexane;	EXAMPLE 242 3-(Dimethylamino)-6,7-dimethyl-1,2,3,4-tetrahydrocarbazole A solution of 11.5 g. of 4-dimethylaminocyclohexanone hydrochloride and 11 g. of <strong>[60481-51-8]3,4-dimethylphenylhydrazine hydrochloride</strong> in 200 ml. of absolute ethyl alcohol was heated under reflux for 6 hours, cooled, filtered, and the filtrate was diluted with ether. The oily precipitate, which was collected by decantation and solidified on standing, was suspended in boiling isopropyl alcohol, filtered and dissolved in methyl alcohol. This solution was diluted with isopropyl alcohol and the methyl alcohol was removed by distillation. The cooled mixture was filtered to give 9.2 g. of a solid which was suspended in ether and treated with dilute potassium hydroxide. The ether extract was evaporated to dryness and the residue was suspended and boiled in hexane and filtered to give 3.2 g. of 3-(dimethylamino)-6,7-dimethyl-1,2,3,4-tetrahydrocarbazole, m.p. 183°-187° C.

References: [1]Patent: US3959309,1976,A .
[2]Patent: US4062864,1977,A .

9
[ 41979-39-9 ]
[ 60481-51-8 ]
8,9-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole [ No CAS ]
7,8-Dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; water; at 75℃; for 3h;	Example 8 7,8-Dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole; To a solution of 1-<strong>[60481-51-8](3,4-dimethylphenyl)hydrazine hydrochloride</strong> (3.7 g, 21.5 mmol) and 4-piperidone hydrochloride monohydrate (3.3 g, 21.5 mmol) in EtOH (63.2 mL) was added 12 N HCl (5.4 ml, 64.5 mmol) at 75° C. The reaction mixture was stirred at 75° C. for 3 h, filtered and rinsed with cold EtOH to a 3:1 mixture of the title compound and its regio-isomer, (4.8 g, 17.6 mmol). The mixture (15 mg) was purified via HPLC (10-20percent CH3CN/H2O), to obtain the title compound (3.3 mg, 0.012 mmol): MS (ES) 201.22 (M+H).; Example 9 8,9-Dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole; The title compound was obtained as a minor product from the synthesis of example 8: MS (ES) 201.22 (M+H).

References: [1]Patent: US2007/27178,2007,A1 .Location in patent: Page/Page column 19-20.

10
[ 1058738-02-5 ]
[ 60481-51-8 ]
[ 1083098-22-9 ]

References: [1]Heterocyclic Communications,2007,vol. 13,p. 359 - 366.

11
[ 141-97-9 ]
[ 60481-51-8 ]
[ 925633-57-4 ]

Yield	Reaction Conditions	Operation in experiment
73%		Example 1; Preparation of 4-[2-(3-cyclohexyl-2-hydroxyphenyl)hydrazin-1-ylidene]-1-(3,4-dimethylphenyl)-3-methyl-4,5-dihydro-1H-pyrazol-5-one; Step 1:; Compound 1a (<strong>[60481-51-8]3,4-dimethylphenylhydrazine hydrochloride</strong>, Acros Catalog Number 408510250) (0.50 g, 2.9 mmol), ethyl acetoacetate (0.38 g, 2.9 mmol), and sodium acetate (0.24 g, 2.9 mmol) were heated in acetic acid (8 mL) to reflux at an oil bath temperature of 155 deg C. for 12 hours. The dark brown solution was allowed to cool, and the solvent was removed under reduced pressure. The brown residue was dissolved in ethyl ether (100 mL), washed sequentially with saturated sodium bicarbonate (3.x.10 mL), and saturated sodium chloride (3.x.10 mL) and dried over sodium sulfate. The solvent was removed under reduced pressure. The mixture was purified by silica gel chromatography with 40percent ethyl acetate-hexanes as eluant to afford Compound 1b as a brown oil which solidified upon standing (0.43 g, 73percent) (i.e., compound (v) in U.S. Pat. No. 7,160,870 B2 herein incorporated by reference in its entirety). 1H NMR (400 MHz, DMSO-d6) delta 11.24 (1H, s), 7.46 (1H, s), 7.39 (1H, dd, J=8.0, 2.0 Hz), 7.15 (1H, d, J=8.0 Hz), 5.34 (1H, s), 2.24 (3H, s), 2.21 (3H, s), 2.09 (3H, s).
71%	With sodium acetate; acetic acid; at 118℃; for 24h;	2-(3,4-Dimethylphenyl)hydrazinium chloride (900 g, 5.21 mol), ethyl acetoacetate (678 g, 5.21 mol), sodium acetate (428 g, 5.21 mol) and glacial acetic acid (10 L) were stirred at 118° C. for about 24 hours. The resulting mixture was cooled and concentrated, and the residue was dissolved in dichloromethane (10 L) and carefully washed with saturated sodium bicarbonate (3.x.3 L). The organic layer was concentrated to afford a solid. The solid was dissolved in ethanol (450 mL) under reflux. Petroleum ether (7.2 L) was slowly added, and the resulting mixture was cooled and filtered to afford the title compound (748 g, 71percent). PXRD analysis provided the diffractogram as shown in FIG. 31.

References: [1]Patent: US2008/139621,2008,A1 .Location in patent: Page/Page column 36.
[2]Patent: US2010/256212,2010,A1 .Location in patent: Page/Page column 16.

12
[ 60481-51-8 ]
[ 42837-61-6 ]
[ 1252577-81-3 ]

References: [1]Tetrahedron,2010,vol. 66,p. 5442 - 5450.

13
[ 59997-51-2 ]
[ 60481-51-8 ]
[ 1025893-78-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	In ethanol; for 5h;Reflux;	a. 5-tert-Butyl-2-(3,4-dimethyl-phenyl)-2H-pyrazol-3-ylamine (Intermediate Ja) A black solution of <strong>[60481-51-8]3,4-dimethylphenyl hydrazine hydrochloride</strong> (Apollo, 1.73 g, 10.0 mmol) and 4,4-dimethyl-3-oxopentanenitrile (1.38 g, 11.0 mmol) in EtOH (20 mL) was stirred at reflux for 5 h. The cooled solution was concentrated in vacuo, redissolved in diethyl ether (20 mL) and washed with aqueous NaOH solution (1M, 20 mL). The aqueous was extracted with diethyl ether (2*20 mL), then the combined organics washed with brine (20 mL), dried (Na2SO4), filtered and concentrated in vacuo to leave the title compound (2.18 g, 90percent). LCMS (Method 3): Rt 2.75 min, m/z 244 [MH+].
90%	In ethanol; for 5h;Reflux;	A black solution of <strong>[60481-51-8]3,4-dimethylphenyl hydrazine hydrochloride</strong> (Apollo, 1.73 g, 10.0 mmol) and 4,4-dimethyl-3-oxopentanenitrile (1.38 g, 11.0 mmol) in EtOH (20 mL) was stirred at reflux for 5 h. The cooled solution was concentrated in vacuo, redissolved in diethyl ether (20 mL) and washed with aqueous NaOH solution (1M, 20 mL). The aqueous was extracted with diethyl ether (2 x 20 mL), then the combined organics washed with brine (20 mL), dried (Na2S04), filtered and concentrated in vacuo to leave the title compound (2.18 g, 90percent). LCMS (Method 3): Rt 2.75 min, m/z 244 [MH+].
490 mg	With triethylamine; In toluene; for 5h;Reflux;	Example 62 3-(tert-butyl)-1-(3,4-dimethylphenyl)-1H-pyrazol-5-amine To a solution of pivaloylacetonitrile (400 mg) in toluene (10 mL) were added <strong>[60481-51-8]3,4-dimethylphenylhydrazine hydrochloride</strong> (520 mg) and triethylamine (0.4 mL) and refluxed with heating for 5 hours. The reaction mixture was added with a saturated sodium hydrogen carbonate aqueous solution. The obtained organic layer was washed with a saturated sodium chloride aqueous solution. The obtained organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The obtained residue was purified on silica gel column chromatography (hexane : ethyl acetate = 4 : 1) to give the titled compound (490 mg) having the following physical data. TCL : Rf 0.41 (Hexane : Ethyl Acetate = 4 : 1).

References: [1]Organic Process Research and Development,2010,vol. 14,p. 650 - 656.
[2]Patent: US2014/364412,2014,A1 .Location in patent: Paragraph 0495; 0496.
[3]Patent: WO2014/195402,2014,A1 .Location in patent: Page/Page column 106.
[4]Organic Process Research and Development,2011,vol. 15,p. 841 - 854.
[5]Patent: EP2842955,2015,A1 .Location in patent: Paragraph 0260.

14
C₁₆H₂₅NO [ No CAS ]
[ 60481-51-8 ]
1-(3,4-dimethylphenyl)-5-(2,6,6-trimethyl-2-cyclohex-1-yl)ethenyl-1H-pyrazole [ No CAS ]
1-(3,4-dimethylphenyl)-3-(2,6,6-trimethyl-2-cyclohex-1-yl)ethenyl-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%; 15%	In ethanol; at 50℃; for 1h;	General procedure: The hydrazines (method 2) or hydrazine hydrochlorides (2 mmol) (method 1) were added in one portion to a stirred solution of enammines (2 mmol) in acidified ethanol (10 mL containing 0.17 mL of HCl 37percent) (method 2) or ethanol (10 mL) (method 1). The resulting solution was stirred for different time at different temperatures. After cooling, several compounds were collected from the reaction mixture by filtration and then crystallized; other compounds were obtained by silica gel chromatography of the residue after removal of the solvent.

References: [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 5293 - 5309.

15
[ 3949-36-8 ]
[ 60481-51-8 ]
[ 1448308-25-5 ]

Yield	Reaction Conditions	Operation in experiment
82%	With acetic acid; In methanol; water; at 60℃; for 0.5h;	General procedure: Phenylhydrazine hydrochloride 6a (0.160 g,1.1 mmol) in mixture of H2O and AcOH was added to a stirred solution of 4-chloro-2-oxo-2H-chromene-3-carbaldehyde 5a (0.208 g,1.0 mmol) in methanol at 60 °C and the reaction was continued for another 30 min at same temperature. The reactionwas monitored by TLC and an orangeered precipitate formation was observed. After completion of the reaction, the reaction mixture was cooled to room temperature, precipitate was filtered off, and the resulted precipitate was dissolved in ethyl acetate and washed with cold water to remove the acetic acid. The organic layer was separated and dried over Na2SO4, solvent was removed under reduced pressure afforded (E)-4-chloro-3-((2-phenylhydrazono)methyl)-2H-chromen-2-one (7a, 0.275 g) as orange color sold in 92percent yield.

References: [1]European Journal of Medicinal Chemistry,2013,vol. 65,p. 389 - 402.

16
[ 60481-51-8 ]
[ 1450908-84-5 ]

References: [1]Organic Letters,2013,vol. 15,p. 4524 - 4527.

17
[ 924-44-7 ]
[ 60481-51-8 ]
[ 1450909-04-2 ]

References: [1]Organic Letters,2013,vol. 15,p. 4524 - 4527.

18
[ 1149371-93-6 ]
[ 60481-51-8 ]
C₃₁H₄₆N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium acetate; In ethanol; at 78℃;	General procedure: A mixture of compound 5 (0.360 g, 1 mmol) and various phenylhydrazines 6a-6ad (0.145-0.225 g,1 mmol) in dry EtOH (10 mL) were stirred at 78°C in the presence of CH3COONa (0.099 g,1.2 mmol). After completion of the reaction monitored by TLC, the solution was then poured into water (10 mL), the white precipitate was filtered and washed with water and dried. The crude product was recrystallized from ethyl acetate/light petroleum ether to give compounds 7a-7ad. Then to a solution of compounds 7a-7ad(0.450-0.529 g, 1 mmol) in toluene (5 mL), 48percent BF3*OEt2 (48percent solution in Et2O, 0.05 mL, 0.17 mmol) was added dropwise and the mixture was heated under a nitrogen atmosphere at 118°C. After completion of the reaction monitored by TLC, water (10 mL) was added to the mixture, which was next neutralized with NaHCO3, and the organic phase was separated and dried over Na2SO4. After evaporation in vacuo, the crude product was purified by column chromatography to give product 9a-9ad.

References: [1]European Journal of Medicinal Chemistry,2013,vol. 65,p. 70 - 82.

19
C₂₃H₃₄O₄ [ No CAS ]
[ 60481-51-8 ]
[ 1448583-07-0 ]

Yield	Reaction Conditions	Operation in experiment
59%	In isopropyl alcohol;Reflux;	General procedure: A mixture of compound 10 (0.376 g, 1 mmol) and various phenylhydrazines 6a-6ad (0.145-0.225 g, 1 mmol) in isopropanol (10 mL) were stirred under reflux. After completion of the reaction monitored by TLC, the reaction mixture was concentrated under vacuum, and extracted with CH3CO2C2H5 and H2O. At last the organic layer was washed with saturated NaCl aqueous solution, dried with Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography on silica to give product 11a-11ad.

References: [1]European Journal of Medicinal Chemistry,2013,vol. 65,p. 70 - 82.

20
[ 95-64-7 ]
[ 60481-51-8 ]

Yield	Reaction Conditions	Operation in experiment
63%		3,4-dimethylaniline (3 kg, 24.75 mol) was added to 19 L of water, heated to 40-50°C to dissolve, and cooled to room temperature.Add 9.3L concentrated hydrochloric acid and continue to cool down to 0-5 °C.Slowly add NaNO2 solution (1.8kg NaNO2 dissolved in 2.7L water),Control temperature does not exceed 10°C; after the dropwise addition, the reaction was carried out at 0-5 ° C for 1 h to form a diazonium salt solution; dissolve Na2SO3 (7.8kg, 61.89mol) in 33L water, warm to 70 ° C, add NaOH solution (1.2kg NaOH dissolved in 12L water), slowly add diazonium salt solution, adjust pH to 6-7 after adding.The reaction was carried out at 70 ° C for 2-3 hours; 150 g of zinc powder was added, and the reaction was continued at 70°C for 1 h, 12 L of concentrated hydrochloric acid was added, and the mixture was heated to 80-85 ° C for 1 h.The mixture was decanted to room temperature, and the crude product was filtered. The crude product was then taken to 30L of ethyl acetate for 3h, filtered, and the filter cake was collected and dried at 40 ° C to obtain about 2.7 kg of product in a yield of about 63percent.
11.8 g		3,4-dimethyl aniline (12.2g, 0.1mol) in 50ml and 20ml of concentrated hydrochloric acidmixed uniformly in water, cooling to below 0 , with mechanical stirring, to which the solution of sodium nitriteaqueous solution (7.6g, 0.11 mol), maintaining the reaction temperature at 0 , stirring was continued for 0.5h,and thereto was added stannous chloride (56.5g, 0.25mol) in concentrated hydrochloric acid (20ml),naturally to room temperature, TLC monitored the reaction was complete feed.Suction filtration, the filter cake dried to give 3,4-dimethylphenylhydrazine hydrochloride (11.8g).

References: [1]Patent: CN109438359,2019,A .Location in patent: Paragraph 0020; 0028; 0029.
[2]Angewandte Chemie - International Edition,2013,vol. 52,p. 12426 - 12429.
Angew. Chem.,2013,vol. 125,p. 12652 - 12656,4.
[3]Patent: CN103360317,2016,B .Location in patent: Paragraph 0095; 0105; 0106; 0107.

21
[ 60481-51-8 ]
[ 38829-72-0 ]

References: [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 12426 - 12429.
Angew. Chem.,2013,vol. 125,p. 12652 - 12656,4.

22
[ 108-24-7 ]
[ 60481-51-8 ]
[ 374924-94-4 ]

References: [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 12426 - 12429.
Angew. Chem.,2013,vol. 125,p. 12652 - 12656,4.
[2]Organic and Biomolecular Chemistry,2014,vol. 12,p. 5469 - 5476.

23
[ 29509-06-6 ]
[ 60481-51-8 ]
[ 1226269-75-5 ]

Yield	Reaction Conditions	Operation in experiment
67%	With hydrogenchloride; In ethanol; for 18h;Reflux;	Intermediate A18: 1-(3,4-Dimethylphenyl)-3-isopropyl-1 H-pyrazol-5-amine. Intermediate A18 To a solution of <strong>[60481-51-8](3,4-dimethylphenyl)hydrazine hydrochloride</strong> (3.0 g, 17 mmol) and 4-methyl- 3-oxopentanenitrile (2.3 mL, 19 mmol) in EtOH (20 mL) was added concentrated hydrochloric acid (1.7 mL, 12 M, 20 mmol). The reaction mixture was heated to reflux for 18 hr and was then cooled to RT and evaporated in vacuo. The residue was partitioned between DCM (50 mL) and water (20 mL). The aq phase was separated and was extracted with DCM (2 x 50 mL). The combined organic extracts were dried and evaporated in vacuo and the residue was purified by flash column chromatography (Si02, 80 g, 0-100percent Et20 in isohexane, gradient elution) to afford the title compound, Intermediate A18 as an orange oil (2.69 g, 67percent); Rl 1.49 min (Method 2 acidic); m/z 230 (M+H)+, (ES+).

References: [1]Patent: WO2014/27209,2014,A1 .Location in patent: Page/Page column 60.

24
[ 1384519-04-3 ]
[ 60481-51-8 ]
[ 1583273-10-2 ]

Yield	Reaction Conditions	Operation in experiment
66%	With acetic acid; In ethanol; at 20℃;Reflux;	General procedure: Compound (E)-ethyl 3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (3a, 100 mg, 0.4 mmol) was dissolved in absolute ethanol (3 mL), phenylhydrazine hydrochloride (5a, 62 mg,0.4 mmol) and acetic acid (0.06 mL, 0.06 mmol) were added atroom temperature, and the resulting mixture was refluxed for 4 h.The reaction was monitored by TLC and after completion of thereaction (TLC), the reaction mixture was brought to room temperatureand solvent was removed under reduced pressure; diluted with water and extracted with ethyl acetate. The organic layer wasdried over Na2SO4, solvent was removed under reduced pressure,and the residue was purified by column chromatography usingsilica gel (hexane/ethyl acetate) provided 6a in 80percent yield. Similarlyother benzoxepinopyrazolones 6b-t were prepared from corresponding3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylates 3bed with substituted phenylhydrazine hydrochlorides 5b-k.

References: [1]European Journal of Medicinal Chemistry,2014,vol. 76,p. 460 - 469.

25
[ 126443-11-6 ]
[ 60481-51-8 ]
[ 1607062-44-1 ]

Yield	Reaction Conditions	Operation in experiment
85%		General procedure: For the synthesis of compounds (1b?12b), 25mL of acetic acid solution of the respective 4-alkoxychalcone (0.01mol) (1a?12a) containing a few drops of hydrochloric acid was heated at 60?65°C for 30min with constant stirring in a round bottom flask. (3,4-Dimethylphenyl)hydrazine hydrochloride (3.45g, 0.02mol) was then added to the reaction flask and the reaction mixture was heated to reflux for 5?6h. After that, the reaction mixture was cooled to room temperature and poured onto the crushed ice. The precipitates thus formed, were filtered, washed with distilled water and dried. The crude products were further purified by silica gel column chromatography using petroleum ether/ethyl acetate (4:1) as the mobile phase to get pure compounds 1b?12b in excellent yields for spectral characterization and fluorescence properties.