[ CAS No. 2243-58-5 ] {[proInfo.proName]}

Name: 2243-58-5|Naphthalen-2-ylhydrazine hydrochloride|95%
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SKU: A221089
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Quality Control of [ 2243-58-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 2243-58-5 ]

Product Details of [ 2243-58-5 ]

CAS No. :	2243-58-5	MDL No. :	MFCD04109481
Formula :	C₁₀H₁₁ClN₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	OXOQKRNEPBHINU-UHFFFAOYSA-N
M.W :	194.66	Pubchem ID :	519950
Synonyms :

Calculated chemistry of [ 2243-58-5 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	2.0
Molar Refractivity :	58.12
TPSA :	38.05 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.44 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	2.88
Log Po/w (WLOGP) :	2.74
Log Po/w (MLOGP) :	2.72
Log Po/w (SILICOS-IT) :	1.47
Consensus Log Po/w :	1.96

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-3.36
Solubility :	0.0841 mg/ml ; 0.000432 mol/l
Class :	Soluble
Log S (Ali) :	-3.34
Solubility :	0.0892 mg/ml ; 0.000458 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.75
Solubility :	0.0345 mg/ml ; 0.000177 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.38

Safety of [ 2243-58-5 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P264-P271-P280-P302+P352-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 2243-58-5 ]

* 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 [ 2243-58-5 ]
Downstream synthetic route of [ 2243-58-5 ]

[ 2243-58-5 ] Synthesis Path-Upstream 1~4

1
[ 563-80-4 ]
[ 2243-58-5 ]
[ 41532-84-7 ]

Reference： [1] Molecules, 2018, vol. 23, # 2,

2
[ 91-59-8 ]
[ 2243-58-5 ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: With hydrogenchloride; sodium nitrite In water for 1 h; Cooling with ice Stage #2: With tin(ll) chloride In water for 3.5 h; Cooling with ice	2.1 2-Naphthylhydrazine hydrochloride [Show Image] NaNO₂ (578 mg, 8.38 mmol) in H₂O (1.2 mL) was slowly added (2 min of addition) over a suspension of 2-naphthylamine (800 mg, 5.59 mmol) in HCl ac. 6.0 M (6 mL) cooled in a H₂O-ice bath. The resulting solution was stirred in H₂O-ice bath for 1 h, and SnCl₂ (3.71 g, 19.56 mol) was added slowly (5 min of addition). The resulting suspension was stirred in H₂O-ice bath for 3.5 h, and then filtered. The solid was successively washed with H₂O at 0 °C (4x8 mL), with H₂O at rt (1x8 mL), with Et₂O at 0 °C (2x4 mL), with Et₂O/hexane (1:1, 2x4 mL) and with hexane (2x5 mL). The solid was dried to yield 690 mg of the desired product (Rf= 0.7 (40percent AcOEt/hexane), cream solid, 63percent yield). NMR-¹H (DMSO-d₆, 250 MHz, δ): 7.81 (m, 2H, ArH); 7.71 (d, J = 7.7 Hz, 1H, ArH); 7.49-7.19 (m, 4H, ArH). MS-El+ m/z: 159.1 (M-HCl+1).

Reference： [1] Patent: EP2395003, 2011, A1, . Location in patent: Page/Page column 12; 17-18
[2] Journal of Medicinal Chemistry, 1990, vol. 33, # 6, p. 1714 - 1720
[3] Angewandte Chemie - International Edition, 2014, vol. 53, # 20, p. 5202 - 5205[4] Angew. Chem., 2014, vol. 126, # 20, p. 5303 - 5306,4

3
[ 580-13-2 ]
[ 2243-58-5 ]

Reference： [1] Chinese Journal of Chemistry, 2018, vol. 36, # 11, p. 1003 - 1006
[2] Journal of Medicinal Chemistry, 2002, vol. 45, # 14, p. 2994 - 3008

4
[ 868394-40-5 ]
[ 2243-58-5 ]

Reference： [1] Journal of Medicinal Chemistry, 2002, vol. 45, # 14, p. 2994 - 3008

[ 2243-58-5 ] Synthesis Path-Downstream 1~88

1
[ 120-57-0 ]
[ 2243-58-5 ]
piperonal-[2]naphthylhydrazone [ No CAS ]

Reference： [1]Archiv der Pharmazie,1907,vol. 245,p. 374

2
[ 2001-23-2 ]
[ 2243-58-5 ]
2-biphenyl-4-yl-1-phenyl-3H-benz[e]indole [ No CAS ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1949,vol. 68,p. 441,458

3
[ 24623-20-9 ]
[ 2243-58-5 ]
[ 63039-86-1 ]

Reference： [1]Journal of Organic Chemistry,1950,vol. 15,p. 131,133

4
[ 14548-38-0 ]
[ 2243-58-5 ]
[ 121936-93-4 ]

Reference： [1]Journal of the Chemical Society,1952,p. 2225,2226

6
[ 5398-10-7 ]
[ 2243-58-5 ]
4-hexyl-1-[2]naphthyl-pyrazolidine-3,5-dione [ No CAS ]

Reference： [1]Canadian Journal of Chemistry,1953,vol. 31,p. 673,682

7
[ 420-04-2 ]
[ 2243-58-5 ]
[2]naphthylamino-guanidine; hydrochloride [ No CAS ]

Reference： [1]Gazzetta Chimica Italiana,1894,vol. 24 I,p. 461

8
[ 692-29-5 ]
[ 2243-58-5 ]
(3H-benz[e]indol-1-yl)-acetic acid ethyl ester [ No CAS ]

Reference： [1]Gazzetta Chimica Italiana,1955,vol. 85,p. 651,656, 657

9
[ 692-29-5 ]
[ 2243-58-5 ]
3-(2-acetylamino-[1]naphthyl)-4-imino-butyric acid [ No CAS ]

Reference： [1]Gazzetta Chimica Italiana,1955,vol. 85,p. 651,656, 657

10
[ 600-35-1 ]
[ 2243-58-5 ]
3-[2]naphthylhydrazono-2-oxo-propionic acid-(N-[2]naphthyl-hydrazide) [ No CAS ]

Reference： [1]Justus Liebigs Annalen der Chemie,1888,vol. 248,p. 91

11
[ 607-83-0 ]
[ 2243-58-5 ]
4-heptyl-1-[2]naphthyl-pyrazolidine-3,5-dione [ No CAS ]

Reference： [1]Canadian Journal of Chemistry,1953,vol. 31,p. 673,682

12
[ 1009-14-9 ]
[ 2243-58-5 ]
2-phenyl-1-propyl-3H-benz[e]indole [ No CAS ]

Reference： [1]Journal of the Chemical Society,1952,p. 2225,2226

13
[ 22009-37-6 ]
[ 2243-58-5 ]
[ 63039-88-3 ]

Reference： [1]Journal of Organic Chemistry,1949,vol. 14,p. 492,496

14
[ 5037-63-8 ]
[ 2243-58-5 ]
8,11-dimethyl-12,13-dihydro-7H-dibenzo[a,g]carbazole [ No CAS ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1950,vol. 69,p. 1053,1078

15
[ 22583-68-2 ]
[ 2243-58-5 ]
9-tert-butyl-12,13-dihydro-7H-dibenzo[a,g]carbazole [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1949,vol. 14,p. 492,496

16
[ 26673-32-5 ]
[ 2243-58-5 ]
9-chloro-12,13-dihydro-7H-dibenzo[a,g]carbazole [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1951,vol. 16,p. 309,312

17
[ 13621-25-5 ]
[ 2243-58-5 ]
[ 667914-67-2 ]

Reference： [1]Journal of Organic Chemistry,1950,vol. 15,p. 950,954

18
[ 614-28-8 ]
[ 2243-58-5 ]
1-[2]naphthyl-3,5-diphenyl-1H-[1,2,4]triazole [ No CAS ]

Reference： [1]Monatshefte fur Chemie,1916,vol. 37,p. 480

19
[ 32281-97-3 ]
[ 2243-58-5 ]
9-bromo-12,13-dihydro-7H-dibenzo[a,g]carbazole [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1951,vol. 16,p. 309,312

20
[ 597-55-7 ]
[ 2243-58-5 ]
4,4-dibenzyl-1-[2]naphthyl-pyrazolidine-3,5-dione [ No CAS ]

Reference： [1]Canadian Journal of Chemistry,1953,vol. 31,p. 673,682

21
[ 7467-80-3 ]
[ 2243-58-5 ]
[ 63020-15-5 ]

Reference： [1]Journal of Organic Chemistry,1951,vol. 16,p. 309,312

22
[ 22531-06-2 ]
[ 2243-58-5 ]
9-ethyl-12,13-dihydro-7H-dibenzo[a,g]carbazole [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1950,vol. 15,p. 950,954

23
[ 19550-57-3 ]
[ 2243-58-5 ]
[ 667914-66-1 ]

Reference： [1]Journal of Organic Chemistry,1950,vol. 15,p. 950,954

24
[ 2243-58-5 ]
[ 591-24-2 ]
[ 111355-17-0 ]

Reference： [1]Journal of Organic Chemistry,1959,vol. 24,p. 487

25
[ 29431-37-6 ]
[ 2243-58-5 ]
7,8,10,11-tetrahydro-benzo[e]thiopyrano[3,4-b]indole 9,9-dioxide [ No CAS ]

Reference： [1]Chemistry of Heterocyclic Compounds,1970,vol. 6,p. 864 - 867
Khimiya Geterotsiklicheskikh Soedinenii,1970,vol. 6,p. 931 - 934

26
[ 2243-58-5 ]
[ 21609-70-1 ]
[ 1781-29-9 ]

Reference： [1]Journal of general chemistry of the USSR,1964,vol. 34,p. 3417 - 3421
Zhurnal Obshchei Khimii,1964,vol. 34,p. 3375 - 3380

27
[ 16676-29-2 ]
[ 2243-58-5 ]
[ 126642-60-2 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 1714 - 1720

28
[ 91-59-8 ]
[ 2243-58-5 ]

Yield	Reaction Conditions	Operation in experiment
63%		2.1 2-Naphthylhydrazine hydrochloride [Show Image] NaNO2 (578 mg, 8.38 mmol) in H2O (1.2 mL) was slowly added (2 min of addition) over a suspension of 2-naphthylamine (800 mg, 5.59 mmol) in HCl ac. 6.0 M (6 mL) cooled in a H2O-ice bath. The resulting solution was stirred in H2O-ice bath for 1 h, and SnCl2 (3.71 g, 19.56 mol) was added slowly (5 min of addition). The resulting suspension was stirred in H2O-ice bath for 3.5 h, and then filtered. The solid was successively washed with H2O at 0 C (4x8 mL), with H2O at rt (1x8 mL), with Et2O at 0 C (2x4 mL), with Et2O/hexane (1:1, 2x4 mL) and with hexane (2x5 mL). The solid was dried to yield 690 mg of the desired product (Rf= 0.7 (40% AcOEt/hexane), cream solid, 63% yield). NMR-1H (DMSO-d6, 250 MHz, delta): 7.81 (m, 2H, ArH); 7.71 (d, J = 7.7 Hz, 1H, ArH); 7.49-7.19 (m, 4H, ArH). MS-El+ m/z: 159.1 (M-HCl+1).

Reference： [1]Patent: EP2395003,2011,A1 .Location in patent: Page/Page column 12; 17-18
[2]Journal of Medicinal Chemistry,1990,vol. 33,p. 1714 - 1720
[3]Angewandte Chemie - International Edition,2014,vol. 53,p. 5202 - 5205
Angew. Chem.,2014,vol. 126,p. 5303 - 5306,4
[4]ACS Medicinal Chemistry Letters,2019,vol. 10,p. 1518 - 1523

29
[ 580-13-2 ]
[ 2243-58-5 ]

Reference： [1]Chinese Journal of Chemistry,2018,vol. 36,p. 1003 - 1006
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 2994 - 3008

30
[ 2243-58-5 ]
1-(5-tert-butyl-2-naphthalen-2-yl-2H-pyrazol-3-yl)-3-phenyl-urea [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 2994 - 3008

31
[ 2243-58-5 ]
[ 205-25-4 ]

Reference： [1]Journal of Organic Chemistry,1959,vol. 24,p. 487
[2]Patent: CN110305057,2019,A

32
[ 2243-58-5 ]
[ 117043-89-7 ]

Reference： [1]Journal of Organic Chemistry,1959,vol. 24,p. 487

33
[ 2243-58-5 ]
[ 21064-50-6 ]

Reference： [1]Journal of Organic Chemistry,1959,vol. 24,p. 487
[2]Recueil des Travaux Chimiques des Pays-Bas,1950,vol. 69,p. 1053,1078

34
[ 2243-58-5 ]
[ 29103-83-1 ]

Reference： [1]Journal of Organic Chemistry,1959,vol. 24,p. 487

35
[ 2243-58-5 ]
[ 111355-28-3 ]

Reference： [1]Journal of Organic Chemistry,1959,vol. 24,p. 487

36
[ 2243-58-5 ]
[ 1203-55-0 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1889,vol. 253,p. 31

37
[ 2243-58-5 ]
[ 172168-01-3 ]
[ 907190-28-7 ]

Yield	Reaction Conditions	Operation in experiment
54%		A mixture of ethyl 3-(3,5-dichlorophenyl)-3-oxopropanoate (500 mg, 1.9 mmol), <strong>[2243-58-5]2-naphthylhydrazine hydrochloride</strong> (372 mg, 1.9 mmol) and glacial acetic acid (19 ml) was refuxed overnight and cooled to room temperature. Mixture was taken to pH 6 using 1.0N aqueous sodium hydroxide and then extracted with ethyl acetate, dried over sodium sulfate, filtered and concentrated. The crude material was purified by flash chromatography on silica gel ( 0-65% ethyl acetate/hexanes) to give 5-(3,5-dichlorophenyl)-2-(2- naphthyl)-2,4-dihydro-3 H-pyrazol-3-one as a brown solid (365 mg, 54%). A mixture of 5-(3,5- dichlorophenyl)-2-(2-naphthyl)-2,4-dihydro-3 H-pyrazol-3-one (360 mg, 1.0 mmol), phosphorous tribromide (3.0 ml, 32 mmol) and anhydrous acetonitrile (1.0 ml) was placed in a Smith microwavable vial and heated in the Smith microwave apparatus for two minutes at 1000C to make mixture homogeneous, then heated to 15O0C until no starting material was observed by tic. The reaction usually was completed in forty minutes. The mixture was carefully poured into ice and stirred at room temperature. Extracted mixture with ethyl acetate, dried over sodium sulfate, filtered and concentrated to give 5-bromo-3-(3,5-dichlorophenyl)-l-(2-naphthyl)-l H-pyrazole as a brown solid (425 mg, 100%). A mixture of 5-bromo-3-(3,5-dichlorophenyl)-l-(2-naphthyl)-l H-pyrazole (441mg, 1.1 mmol), 3-buryn-l- ol (0.24 ml, 3.14 mmol), degassed triethylamine (10.2 ml), palladium tetrakistriphenylphosphine (194 mg, 0.17 mmol) and copper (I)bromide dimethyl sulfide (65 mg, 0.32 mmol) was heated to 7O0C for a few hours until no starting material was observed by tic. Mixture was cooled, concentrated, washed with brine and extracted with ethyl acetate. Organic extracts were combined, dried over sodium sulfate, filtered and concentrated to give a crude material which was further purified via flash chromatography on silica gel (0-75% ethyl acetate/hexanes). This afforded 4-[3-(3,5-dichlorophenyl)-l-Hpyrazol-5-yl]but-3-yn-l- ol as a tan solid (318 mg, 74%). 4-[3-(3,5-Dichlorophenyl)-l-Hpyrazol-5-yl]but-3-yn-l-ol (318 mg, 0.8 mmol), 5% platinum on carbon (200 mg) and ethyl acetate (20 ml) was stirred under hydrogen EPO <DP n="26"/>atmosphere at one atmosphere of pressure overnight. The mixture was filtered through a celite pad, washing with ethyl acetate and the filtrate concentrated to give 4-[3-(3,5-dichlorophenyl)-l-(2-naphthyl)- 1 H-pyrazol-5-yl]butan-l-ol as a white solid (255 mg, 80%). A mixture of 4-[3-(3,5-dichlorophenyl)-l-(2- naphthyl)-l H-pyrazol-5-yl]butan-l-ol (255 mg, 0.62 mmol), pyridinium dichromate (816 mg, 2.17 mmol) and dimethylformamide (3.1 ml) was stirred at room temperature overnight. Purification of the reaction mixture via flash chromatography on silica gel (0-40% ethyl acetate/hexanes) afforded 4-[3- (3,5-dichlorophenyl)-l-(2-naphthyl)-l Hpyrazol-5-yl]butanoic acid as a white solid (159 mg, 60%). MS (ESI) 426 (M+).

Reference： [1]Patent: WO2006/88813,2006,A1 .Location in patent: Page/Page column 24-25

38
[ 69316-09-2 ]
[ 2243-58-5 ]
[ 907190-89-0 ]

Yield	Reaction Conditions	Operation in experiment
		The mixture of <strong>[2243-58-5]2-naphthylhydrazine hydrochloride</strong> (1.81g, 9.33mmol), 3-(3,5-dichlorophenyl)-3- oxopropanenitrile (2.44g, 11.45mmol) in 50ml toluene was heated to 13O0C for 12 hours. The reaction mixture was quenched with aqueous sodium bicarbonate (10OmL), extracted with EtOAc (3 x 10OmL) and the combined organic extracts washed with brine. The organic phase was dried over Na2SC^ and concentrated in vacuo. The crude purified by liquid chromatography on silica gel using an ISCO single channel system (Etaexane/EtOAc: 10/0 to 1/9) to give 3-(3,5-dichlorophenyl)-l-(2-naphthyl)-lH-pyrazol- 5-amine as product. 1H NMR (CD3Cl3, 500 MHz) delta 8.055-8.051 (d, IH), 8.00-7.98 (d, IH), 7.90-7.88 EPO <DP n="42"/>(m, 2H), 7.78-7.60 (dd, IH), 7.726-7.722 (m, 2H), 7.57-7.53 (m, 2H), 7.29-7.28 (t, IH), 5.96 (s, IH), 3.95 (s, 2H). MS (ESI) 353.97 (M+-I-H).

Reference： [1]Patent: WO2006/88813,2006,A1 .Location in patent: Page/Page column 40-41

39
[ 113-24-6 ]
[ 2243-58-5 ]
[ 42178-83-6 ]

Reference： [1]Chemistry of Heterocyclic Compounds,2009,vol. 45,p. 1464 - 1468

40
[ 1271-55-2 ]
[ 2243-58-5 ]
[ 68-12-2 ]
[ 1259930-40-9 ]

Reference： [1]Russian Chemical Bulletin,2010,vol. 59,p. 405 - 410

41
[ 453-72-5 ]
[ 2243-58-5 ]
[ 945528-20-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4828 - 4831

42
[ 2243-58-5 ]
[ 945528-23-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4828 - 4831

43
[ 2243-58-5 ]
[ 1116572-61-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4828 - 4831

44
[ 2243-58-5 ]
[ 615-79-2 ]
[ 330803-41-3 ]
[ 330803-40-2 ]

Yield	Reaction Conditions	Operation in experiment
66%; 7%		2.2 Ethyl 5-methyl-1-(2-naphthyl)-1H-pyrazole-3-carboxylate; [Show Image] Ethyl acetopyruvate (544 mg, 3.44 mmol) was added over a suspension of the starting hydrazine (670 mg, 3.44 mmol) in AcOH (5 mL). The resulting suspension was refluxed for 1 h, then it was allowed to cool to r.t. and diluted with CH2Cl2 (15 mL). The organic phase was successively washed with H2O (2x20 mL), with NaOH ac. 10% (1x20 mL) and again with H2O (1x20 mL). The organic phase was dried over Na2SO4 anh., filtered and concentrated to dryness. The residue was purified by flash column chromatography in silica gel (15-41% AcOEt/hexane), to yield 68 mg of isomer a (Rf= 0.8 (20% AcOEt/hexane), orange solid, 7% yield) and 640 mg of isomer b (Rf= 0.6 (20% AcOEt/hexane), organge solid, 66% yield) NMR-1H isomer b (CDCl3, 250 MHz, delta): 7.95-7.84 (m, 4H, ArH); 7.60-7.51 (m, 3H, ArH); 6.78 (s, 1H, ArH); 4.43 (c, J = 7.1 Hz, 2H, CH2); 2.38 (s, 3H, CH3); 1.40 (t, J = 7.1 Hz, 3H, CH3). NMR-1H isomer a (CDCl3, 250 MHz, delta): 7.91-7.85 (m, 4H, ArH); 7.53-7.48 (m, 3H, ArH); 6.86 (s, 1H, ArH); 4.22 (c, J = 7.1 Hz, 2H, CH2); 2.39 (s, 3H, CH3); 1.20 (t, J = 7.1 Hz, 3H, CH3).

Reference： [1]Patent: EP2395003,2011,A1 .Location in patent: Page/Page column 12-13; 18

45
[ 2243-58-5 ]
[ 1351437-80-3 ]

Reference： [1]Patent: EP2395003,2011,A1

46
[ 2243-58-5 ]
[ 1351437-86-9 ]

Reference： [1]Patent: EP2395003,2011,A1

47
[ 2243-58-5 ]
[ 1351437-81-4 ]

Reference： [1]Patent: EP2395003,2011,A1

48
[ 2243-58-5 ]
[ 1351437-87-0 ]

Reference： [1]Patent: EP2395003,2011,A1

49
[ 2243-58-5 ]
[ 1351437-88-1 ]

Reference： [1]Patent: EP2395003,2011,A1

50
[ 6290-17-1 ]
[ 2243-58-5 ]
[ 1192140-15-0 ]
[ 1357362-21-0 ]

Yield	Reaction Conditions	Operation in experiment
		Example 26 (Comparative): Adaptation of the process by Ueda et al. 1982 for the preparation of the compound of formula (VII)/(VIIa) 5-methyl-l-(naphthalen-2-yl)-lH- pyrazol-3-olNaphthalen-2-ylhydrazine hydrochloride (30 g) and NaOMe (20,85 g) were slurried in toluene (300 ml) and heated to 80/85 °C. Ethyl 2-(2,4-dimethyl-l,3-dioxolan-2- yl)acetate (30,6 ml) was added and maintained for 90 min. Ethyl 2-(2,4-dimethyl-l,3- dioxolan-2-yl)acetate (8,2 ml) and NaOMe (2,5 g) were added and maintained for 2 h. NaOMe (1,7 g) was added and maintained for 1 h. The mixture was cooled to room temperature, water (450 ml) was added and pH adjusted to 6-8 with aqueous HC1. The organic layer was concentrated to dryness under vacuum and methanol (450 ml), HC1 35percent (18 ml) and water (54 ml) were added. The mixture was heated to reflux for 90 min and concentrated under vacuum to 165 ml of final volume. Water (120 ml) and CH2C12 (120 ml) were added and pH adjusted to 12,2-12,7 (basified with NaOH 25percent). Upper organic layer was discarded, and pH of lower aqueous layer was adjusted to 5,0- 7,0 with acetic acid 80percent. The solid was filtered, washed with water (45 ml) and slurried in ethyl acetate (102 ml) 2 h at 20/25 °C. The solid was filtered, washed with ethyl acetate (15 ml) and dried to yield 20,24 g (46percent) of a mixture [5-methyl-l- (naphthalen-2-yl)-lH-pyrazol-3-ol]: [3-methyl-l-(naphthalen-2-yl)-lH-pyrazol-5-ol] (80:20).
		Example 26Adaptation of the process by Ueda et al.1982 for the preparation of 5-methyl-1-(naphthalen-2-yl)-1H -pyrazol-3-olNaphthalen-2-ylhydrazine hydrochloride (30 g) and NaOMe (20,85 g) were slurried in toluene (300 ml) and heated to 80/85 °C. Ethyl 2-(2,4-dimethyl-1,3-dioxolan-2-yl)acetate (30,6 ml) was added and maintained for 90 min.Ethyl 2-(2,4-dimethyl-1,3-dioxolan-2-yl)acetate (8,2 ml) and NaOMe (2,5 g) were added and maintained for 2 h. NaOMe (1,7 g) was added and maintained for 1 h.The mixture was cooled to room temperature, water (450 ml) was added and pH adjusted to 6-8 with aqueous HCl.The organic layer was concentrated to dryness under vacuum and methanol (450 ml), HCl 35percent (18 ml) and water (54 ml) were added.The mixture was heated to reflux for 90 min and concentrated under vacuum to 165 ml of final volume.Water (120 ml) and CH2Cl2 (120 ml) were added and pH adjusted to 12,2-12,7 (basified with NaOH 25percent).Upper organic layer was discarded, and pH of lower aqueous layer was adjusted to 5,0-7,0 with acetic acid 80percent.The solid was filtered, washed with water (45 ml) and slurried in ethyl acetate (102 ml) 2 h at 20/25 °C.The solid was filtered, washed with ethyl acetate (15 ml) and dried to yield 20,24 g (46percent) of a mixture [5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-ol]: [3-methyl-1-(naphthalen-2-yl)-1H-pyrazol-5-ol] (80:20).

Reference： [1]Patent: WO2012/13755,2012,A1 .Location in patent: Page/Page column 48
[2]Patent: EP2418192,2012,A1 .Location in patent: Page/Page column 26-27

51
[ 1356907-02-2 ]
[ 2243-58-5 ]
[ 1356907-03-3 ]

Yield	Reaction Conditions	Operation in experiment
37%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In water; for 0.25h;Product distribution / selectivity;	Example 3 : Preparation of the compound of formula (V) 2-(2,4-dimethyl-L3-dioxolan- 2-yl)-N'-(naphthalen-2-yl)acetohydrazide using EDCA solution of EDC (1.307 g, 6.82 mmol) in 10 mL of water was added to a suspension of the compound of formula (IV) naphthalen-2-ylhydrazyne hydrochloride (1.236 g, 6.35 mmol) and the compound (Ila) 2-(2,4-dimethyl-l,3-dioxolan-2-yl)acetic acid (1.072 g, 6.69 mmol) in 30 mL of water. After 15 minutes the reaction mixture was filtered and the solution was washed with 40 mL of 10"3M HCl and then 40 mL of water. The organic layer was dried over MgS04 and after filtering the solvent was evaporated to dryness. The corresponding 0.705 g (37%) of the title hydrazide was obtained. Further cyclation was not carried out.
37%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In water; for 0.25h;	Example 19 Preparation of 2-(2,4-dimethyl-1,3-dioxolan-2-yl)-N'-(naphthalen-2- yl)acetohydrazide using EDC A solution of EDC (1.307 g, 6.82 mmol) in 10 mL of water was added to a suspension of naphthalen-2-ylhydrazyne hydrochloride (1.236 g, 6.35 mmol), 2-(2,4-dimethyl-1,3-dioxolan-2-yl)acetic acid (1.072 g, 6.69 mmol) in 30 mL of water. After 15 minutes the reaction mixture was filtered and the solution was washed with 40 mL of 10-3M HCl and then 40 mL of water. The organic layer was dried over MgSO4 and after filtering the solvent was evaporated to dryness. The corresponding 0.705 g (37%) of the title hydrazide was obtained. Further cyclation was not carried out.

Reference： [1]Patent: WO2012/13755,2012,A1 .Location in patent: Page/Page column 31-32
[2]Patent: EP2418192,2012,A1 .Location in patent: Page/Page column 25

52
[ 1356907-05-5 ]
[ 2243-58-5 ]
[ 1356907-03-3 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 20℃; for 3h;Product distribution / selectivity;	Example 22: Preparation of the compound of formula (VHV(VIIa) 5-methyl-l- (naphthalen-2-yl)-lH-pyrazol-3-ol via mixed anhydrides of formula (III)Over a solution of the compound (Ila) 2-(2,4-dimethyl-l,3-dioxolan-2-yl)acetic acid (4.320 g, 26.97 mmol) in 50 mL of CH2C12, ethyl chloroformate (2.5 mL, 25.75 mmol) at 0 C was added. Keeping temperature at 0 C anhydrous Et3N (3.9 mL, 28.26 mmol) was slowly added to obtain the compound of formula (III) ethyl carbonic 2-(2,4- dimethyl-l,3-dioxolan-2-yl)acetic anhydride. After 20 minutes of stirring, a suspension of the compound of formula (IV) naphthalen-2-ylhydrazyne hydrochloride (5.007 g, 25.69 mmol) and Et3N (3.9 mL, 28.26 mmol) in 35 mL of anhydrous CH2C12 was added at r.t. over the mixed anhydride. After 3 hours solvent was evaporated to obtain the compound of formula (V) 2-(2,4-dimethyl-l,3-dioxolan-2-yl)-N'-(naphthalen-2-yl) acetohydrazide.The dry crude was dissolved in 130 mL of MeOH. A solution of HCl in water (3 mL of concentrated HCl in 7 mL of water) was added and the reaction was refluxed for one hour to hydrolyze the ketal group, thus obtaining the compound of formula (VI) N'- (naphthalen-2-yl)-3-oxobutanehydrazide which subsequently cyclises. The reaction was allowed to cool to room temperature. The crude was then concentrated in a rotavapor so as to reduce as much as possible the MeOH volume. This evaporated crude was basified to pH « 14 with 2M NaOH (« 40 mL) obtaining a precipitate. The basified crude was filtered, the solid was discarded and the filtrate thus obtained was acidified with dilute AcOH (1 :5 with water) to pH « 7. During the neutralisation a new precipitate was observed, which was then filtered and dried in a desiccator. 5.612 g (97%) of a solid was obtained corresponding to the title compound according to 1H MR. The isomeric ratio obtained for [5-methyl-l-(naphthalen-2-yl)-lH-pyrazol-3-ol] : [3-methyl-l-(naphthalen-2-yl)-lH-pyrazol-5-ol] was 98:2.

Reference： [1]Patent: WO2012/13755,2012,A1 .Location in patent: Page/Page column 44-45

53
[ 1356907-06-6 ]
[ 2243-58-5 ]
[ 1356907-03-3 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In toluene; at 20℃; for 16h;Cooling with ice;Product distribution / selectivity;	This solution of acid chloride in toluene was cannulated over a solution of the compound of formula (IV) naphthalen-2-ylhydrazyne hydrochloride (5.001 g, 25.69 mmol) and Et3N (10.1 mL, 72.7 mmol) in 20 mL of toluene in ice bath was added dropwise. Once acid chloride was added the cool bath was removed and the mixture was stirred at r.t. for 16 hours. After this period of time, the organic layer was washed with 80 mL of water and dried over MgS04 and was filtered, and concentrated then to dryness to obtain the compound of formula (V) 2-(2,4-dimethyl-l,3-dioxolan-2-yl)-N'- (naphthalen-2-yl) acetohydrazide.

Reference： [1]Patent: WO2012/13755,2012,A1 .Location in patent: Page/Page column 47

54
[ 1356907-02-2 ]
[ 2243-58-5 ]
[ 1192140-15-0 ]

Yield	Reaction Conditions	Operation in experiment
97%		Example 20 Preparation of 5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-ol via mixed anhydrides Over a solution of 2-(2,4-dimethyl-1,3-dioxolan-2-yl)acetic acid (4.320 g, 26.97 mmol) in 50 mL of CH2Cl2, ethyl chloroformate (2.5 mL, 25.75 mmol) at 0 C was added. Keeping temperature at 0 C anhydrous Et3N (3.9 mL, 28.26 mmol) was slowly added. After 20 minutes of stirring, a suspension of naphthalen-2-ylhydrazyne hydrochloride (5.007 g, 25.69 mmol) and Et3N (3.9 mL, 28.26 mmol) in 35 mL of anhydrous CH2Cl2 was added at r.t. over the mixed anhydride. After 3 hours solvent was evaporated. The dry crude was dissolved in 130 mL of MeOH. A solution of HCl in water (3 mL of concentrated HCl in 7 mL of water) was added and the reaction was refluxed for one hour. The reaction was allowed to cool to room temperature. The crude was then concentrated in a rotavapor so as to reduce as much as possible the MeOH volume. This evaporated crude was basified to pH ? 14 with 2M NaOH (? 40 mL) obtaining a precipitate. The basified crude was filtered, the solid was discarded and the filtrate thus obtained was acidified with dilute AcOH (1:5 with water) to pH ? 7. During the neutralisation a new precipitate was observed, which was then filtered and dried in a desiccator. 5.612 g (97%) of a solid was obtained corresponding to the title compound according to 1H NMR. The isomeric ratio obtained for [5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-ol] : [3-methyl-1-(naphthalen-2-yl)-1H-pyrazol-5-ol] was 98:2.

Reference： [1]Patent: EP2418192,2012,A1 .Location in patent: Page/Page column 25

55
[ 2243-58-5 ]
3-(anthracen-9-yl)-1-p-tolylprop-2-en-1-one [ No CAS ]
[ 1337561-41-7 ]

Reference： [1]Journal of the Brazilian Chemical Society,2011,vol. 22,p. 1286 - 1298

56
[ 2243-58-5 ]
C₁₅H₁₄N₂O [ No CAS ]