[ CAS No. 4488-40-8 ] {[proInfo.proName]}

Name: 4488-40-8|4-Methyl-1-naphthoic acid|97%
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SKU: A209848
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Quality Control of [ 4488-40-8 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 4488-40-8 ]

CAS No. :	4488-40-8	MDL No. :	MFCD00671557
Formula :	C₁₂H₁₀O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SIVYRLBDAPKADZ-UHFFFAOYSA-N
M.W :	186.21	Pubchem ID :	3014285
Synonyms :

Calculated chemistry of [ 4488-40-8 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.08
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	55.87
TPSA :	37.3 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) :	-4.98 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.32
Log Po/w (XLOGP3) :	3.46
Log Po/w (WLOGP) :	2.85
Log Po/w (MLOGP) :	2.92
Log Po/w (SILICOS-IT) :	2.82
Consensus Log Po/w :	2.67

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-3.64
Solubility :	0.043 mg/ml ; 0.000231 mol/l
Class :	Soluble
Log S (Ali) :	-3.92
Solubility :	0.0221 mg/ml ; 0.000119 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.83
Solubility :	0.0272 mg/ml ; 0.000146 mol/l
Class :	Soluble

Medicinal Chemistry

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

Safety of [ 4488-40-8 ]

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

Application In Synthesis of [ 4488-40-8 ]

* 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.

Upstream synthesis route of [ 4488-40-8 ]
Downstream synthetic route of [ 4488-40-8 ]

[ 4488-40-8 ] Synthesis Path-Upstream 1~18

1
[ 124-38-9 ]
[ 90-12-0 ]
[ 4488-40-8 ]

Reference： [1] Journal of Organic Chemistry, 2010, vol. 75, # 22, p. 7855 - 7862
[2] Chemistry Letters, 2002, # 1, p. 102 - 103

2
[ 6627-78-7 ]
[ 556-63-8 ]
[ 4488-40-8 ]

Reference： [1] Synthesis, 2006, # 18, p. 3106 - 3110

3
[ 33738-48-6 ]
[ 4488-40-8 ]

Reference： [1] Tetrahedron, 2004, vol. 60, # 30, p. 6295 - 6310
[2] Tetrahedron Letters, 1984, vol. 25, # 20, p. 2139 - 2142

4
[ 28418-86-2 ]
[ 4488-40-8 ]

Reference： [1] Canadian Journal of Chemistry, 1981, vol. 59, p. 2629 - 2641
[2] Collection of Czechoslovak Chemical Communications, 2000, vol. 65, # 3, p. 385 - 394

5
[ 36062-93-8 ]
[ 4488-40-8 ]

Reference： [1] Journal of the American Chemical Society, 1993, vol. 115, # 6, p. 2180 - 2190

6
[ 6627-78-7 ]
[ 4488-40-8 ]

Reference： [1] Journal of the American Chemical Society, 1993, vol. 115, # 6, p. 2180 - 2190

7
[ 124-38-9 ]
[ 17075-39-7 ]
[ 4488-40-8 ]

Reference： [1] Organic Letters, 2012, vol. 14, # 22, p. 5680 - 5683

8
[ 571-58-4 ]
[ 35461-84-8 ]
[ 33738-48-6 ]
[ 4488-40-8 ]

Reference： [1] Tetrahedron Letters, 1984, vol. 25, # 20, p. 2139 - 2142
[2] Tetrahedron Letters, 1984, vol. 25, # 20, p. 2139 - 2142

9
[ 571-58-4 ]
[ 33738-48-6 ]
[ 4488-40-8 ]
[ 126558-73-4 ]

Reference： [1] Tetrahedron Letters, 1989, vol. 30, # 35, p. 4677 - 4680
[2] Tetrahedron Letters, 1989, vol. 30, # 35, p. 4677 - 4680

10
[ 141-82-2 ]
[ 90-12-0 ]
[ 33738-48-6 ]
[ 4488-40-8 ]

Reference： [1] Bulletin of the Chemical Society of Japan, 1989, vol. 62, # 2, p. 545 - 550

11
[ 571-58-4 ]
[ 4488-40-8 ]

Reference： [1] Tetrahedron Letters, 1984, vol. 25, # 20, p. 2139 - 2142

12
[ 2206-74-8 ]
[ 4488-40-8 ]

Reference： [1] Journal of the Chemical Society, 1965, p. 833 - 843

13
[ 5261-50-7 ]
[ 4488-40-8 ]

Reference： [1] Chemische Berichte, 1951, vol. 84, p. 636,640
[2] Chemische Berichte, 1951, vol. 84, p. 636,640

14
[ 57322-44-8 ]
[ 4488-40-8 ]

Reference： [1] Chemische Berichte, 1951, vol. 84, p. 636,640

15
[ 49675-07-2 ]
[ 4488-40-8 ]

Reference： [1] Chemische Berichte, 1951, vol. 84, p. 636,640

16
[ 28418-86-2 ]
[ 4488-40-8 ]
[ 32405-50-8 ]

Reference： [1] Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical & Analytical, 1980, vol. 19, # 7, p. 646 - 649

17
[ 124-38-9 ]
[ 115913-58-1 ]
[ 4488-40-8 ]

Reference： [1] Bulletin de la Societe Chimique de France, 1966, p. 3901 - 3904

18
[ 571-58-4 ]
[ 33738-48-6 ]
[ 4488-40-8 ]
[ 35461-84-8 ]

Reference： [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1985, p. 269 - 272

[ 4488-40-8 ] Synthesis Path-Downstream 1~88

1
[ 57322-44-8 ]
[ 4488-40-8 ]

Reference： [1]Chemische Berichte,1951,vol. 84,p. 636,640

2
[ 4488-40-8 ]
[ 476-73-3 ]

Reference： [1]Journal of the American Chemical Society,1952,vol. 74,p. 116,117

3
[ 4488-40-8 ]
[ 605-70-9 ]

Reference： [1]Chemische Berichte,1922,vol. 55,p. 1854

4
[ 4488-40-8 ]
[ 87700-67-2 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; for 0.25h;Heating / reflux;	To a stirred solution of 0.080 g (0.50 mmol) of 1-propylindole in 1.5 mL of dry CH2Cl2 at 0 C. under N2 was added dropwise 0.75 mL (0.75 mmol) of Me2AlCl (1 M in hexanes). The solution was stirred at 0 C. for 30 min and a solution of 0.122 g (0.6 mmol) of freshly prepared 4-methyl-1-naphthoyl chloride in 1.5 mL of CH2Cl2. The acid chloride was prepared form 0.122 g (0.60 mmol) of 4-methyl-1-naphthoic acid to which was added dropwise 1 mL of thionyl chloride at a rate sufficient to maintain a steady evolution of gas. This solution was heated at reflux for 15 min, cooled to ambient temperature and the excess thionyl chloride was removed in vacuo to give the acid chloride which was used without further purification. The deep red acylation reaction mixture was stirred at 0 C. until the reaction was complete as indicated by tlc (approximately 1 h). The reaction mixture was poured carefully into iced 1 M aqueous HCl and extracted with three portions of CH2Cl2. The combined extracts were washed wth three portions of aqueous NaHCO3, dried (MgSO4) and the solvent was removed in vacuo to give the crude product. After chromatography (petroleum ether:ethyl acetate, 9: 1) there was obtained 0.140 g (86%) of indole 41 as a white solid. Recrystallization from hexanes/ethyl acetate gave the analytical sample: m.p. 207-208 C.; 1H NMR (300 MHz, CDCl3) delta 0.90 (t, J=7.3 Hz, 3H), 1.81-1.88 (m, 2H), 2.78 (s, 3H), 4.03 (t, J=7.0 Hz, 2H), 7.37-7.38 (m, 5H), 7.48-7.59 (m, 3H), 8.09 (d, J=8.2 Hz, 1H), 8.27 (d, J=8.2 Hz, 1H), 8.52-8.54 (m, 1H); 13C NMR (75.5 MHz, CDCl3) delta 11.3, 19.7, 23.1, 48.7, 109.9, 117.6, 122.7, 122.9, 123.5, 124.2, 125.5, 125.8, 126.1, 126.3, 126.6, 127.0, 130.9, 132.8, 136.6, 137.0, 137.5, 137.9, 192.2; Anal. Calcd for C23H21NO: C, 84.37; H, 6.46; N, 4.28; Found: C, 84.25; H, 6.46; N, 4.30.
	With thionyl chloride; In dichloromethane; for 4h;Reflux; Inert atmosphere;	4-Methyl-l-napthoyl chloride[0151] To a solution of 0.35 g (1.89 mmol) of 4-methyl-l-napthoic acid in 3 mL of dry dichloromethane under argon, was added 2.5 ml (34.3 mmol) of thionyl chloride. The solution was refluxed for 4 hrs and the solvent and excess thionyl chloride were removed by vacuum distillation to give a red oil, which was used without further purification.
	With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 2h;	Step B: 4-Methylnaphthalenecarbonyl chloride.; Step B: 4-Methylnaphthalenecarbonyl chloride. Oxalyl chloride (0.53 niL, 6.1 mmol), followed by anhydrous DMF (2-3 drops) was added to a stirred solution of 4-methylnaphthalenecarboxylic acid (0.227 g, 1.22 mmol) in CH2Cl2 (10 mL). The mixture was stirred at room temperature for 2 h, evaporated and dried under vacuum for 0.5 h. to give the title acid chloride , which was used without further purification in step A.

With thionyl chloride;

Step B. 2-(4-Methyl-l-naphthalenyl)-4H-pyrido [3,2-d] [1,3]oxazin-4-one; Following the procedure for Step B in Example 1, a suspension of 3-amino-2- pyridinecarboxylic acid (414 mg, 3.0 mmol) in CH2Cl2 (10 mL) and DIPEA (1.25 mL, 7.2 mmol) was treated with 4-methyl-l-naphthalenecarbonyl chloride, prepared from 4- methyl-1-naphthalenecarbonylic acid (590 mg, 3.17 mmol) with thionyl chloride (4.11 g, 35 mmol), and then with HATU (1.25 g, 3.3 mmol) in DMF (10 mL). The title compound was formed and directly used in Step A.

Reference： [1]Journal of the Chemical Society,1931,p. 489,495
[2]Chemische Berichte,1922,vol. 55,p. 1854
[3]Journal of Medicinal Chemistry,1995,vol. 38,p. 3094 - 3105
[4]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 539 - 549
[5]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 89 - 112
[6]Journal of Medicinal Chemistry,2005,vol. 48,p. 5813 - 5822
[7]Patent: US2005/9903,2005,A1 .Location in patent: Page 23
[8]Heteroatom Chemistry,2011,vol. 22,p. 707 - 714
[9]Patent: WO2012/24670,2012,A2 .Location in patent: Page/Page column 44
[10]Journal of Molecular Structure,2016,vol. 1103,p. 45 - 55
[11]Chemical Communications,2016,vol. 52,p. 6709 - 6711
[12]Organic Letters,2018,vol. 20,p. 3132 - 3135
[13]Patent: WO2007/139464,2007,A1 .Location in patent: Page/Page column 52
[14]Patent: WO2005/115986,2005,A1 .Location in patent: Page/Page column 57
[15]Indian Journal of Heterocyclic Chemistry,2017,vol. 27,p. 1 - 11

5
[ 124-38-9 ]
[ 115913-58-1 ]
[ 4488-40-8 ]

Reference： [1]Bulletin de la Societe Chimique de France,1966,p. 3901 - 3904

6
[ 2206-74-8 ]
[ 4488-40-8 ]

Reference： [1]Journal of the Chemical Society,1965,p. 833 - 843

7
[ 4488-40-8 ]
[ 95-55-6 ]
[ 52823-79-7 ]

Reference： [1]Helvetica Chimica Acta,1974,vol. 57,p. 945 - 979

8
[ 4488-40-8 ]
[ 95-84-1 ]
[ 52823-80-0 ]

Reference： [1]Helvetica Chimica Acta,1974,vol. 57,p. 945 - 979

9
[ 4488-40-8 ]
[ 4363-03-5 ]
[ 52823-82-2 ]

Reference： [1]Helvetica Chimica Acta,1974,vol. 57,p. 945 - 979

10
[ 571-58-4 ]
[ 35461-84-8 ]
[ 33738-48-6 ]
[ 4488-40-8 ]

Reference： [1]Tetrahedron Letters,1984,vol. 25,p. 2139 - 2142
[2]Tetrahedron Letters,1984,vol. 25,p. 2139 - 2142

12
[ 571-58-4 ]
[ 33738-48-6 ]
[ 4488-40-8 ]
[ 35461-84-8 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions II,1985,p. 269 - 272

13
[ 33738-48-6 ]
[ 4488-40-8 ]

Reference： [1]Tetrahedron,2004,vol. 60,p. 6295 - 6310
[2]Tetrahedron Letters,1984,vol. 25,p. 2139 - 2142

14
[ 28418-86-2 ]
[ 4488-40-8 ]

Reference： [1]Canadian Journal of Chemistry,1981,vol. 59,p. 2629 - 2641
[2]Collection of Czechoslovak Chemical Communications,2000,vol. 65,p. 385 - 394

15
[ 28418-86-2 ]
[ 4488-40-8 ]
[ 32405-50-8 ]

Reference： [1]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,1980,vol. 19,p. 646 - 649

16
[ 4488-40-8 ]
[ 57322-44-8 ]

Reference： [1]Journal of the American Chemical Society,1993,vol. 115,p. 2180 - 2190
[2]Canadian Journal of Chemistry,1981,vol. 59,p. 2629 - 2641
[3]Journal of the American Chemical Society,1963,vol. 85,p. 1088 - 1093

17
[ 36062-93-8 ]
[ 4488-40-8 ]

Reference： [1]Journal of the American Chemical Society,1993,vol. 115,p. 2180 - 2190

18
[ 6627-78-7 ]
[ 556-63-8 ]
[ 4488-40-8 ]

Reference： [1]Synthesis,2006,p. 3106 - 3110

19
[ 4488-40-8 ]
1-[(N-methylpiperidin-2-yl)methyl]-3-(4-methyl-1-naphthoyl)indole [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5813 - 5822

20
[ 4488-40-8 ]
[ 824430-37-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 89 - 112

21
[ 4488-40-8 ]
JWH-120 [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 89 - 112

22
[ 4488-40-8 ]
JWH-148 [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 89 - 112

23
[ 4488-40-8 ]
4,4'-dimethyl[2,2']binaphthalenyl-1,1'-diol [ No CAS ]

Reference： [1]Tetrahedron,2004,vol. 60,p. 6295 - 6310

24
[ 4488-40-8 ]
[ 133438-58-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 539 - 549
[2]Journal of Medicinal Chemistry,1995,vol. 38,p. 3094 - 3105

25
[ 4488-40-8 ]
3-(4-methyl-naphthalen-1-ylmethyl)-1-pentyl-1H-indole [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 539 - 549

26
[ 4488-40-8 ]
JWH-122 [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 539 - 549

27
[ 4488-40-8 ]
2-methyl-3-(4-methyl-naphthalen-1-ylmethyl)-1-pentyl-1H-indole [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 539 - 549

28
[ 4488-40-8 ]
JWH-149 [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 539 - 549

29
[ 4488-40-8 ]
3-(4-methyl-naphthalen-1-ylmethyl)-1-(2-morpholin-4-yl-ethyl)-1H-indole [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 539 - 549

30
[ 4488-40-8 ]
[ 57322-46-0 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775

31
[ 4488-40-8 ]
[ 105904-00-5 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775

32
[ 4488-40-8 ]
[ 62855-40-7 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775
[2]Patent: US2012/77765,2012,A1

33
[ 4488-40-8 ]
[ 219685-15-1 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775

34
[ 4488-40-8 ]
4-(imidazole-1-carbonyl)-naphthalene-1-carbaldehyde [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775

35
[ 4488-40-8 ]
[ 1026050-35-0 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775

36
[ 4488-40-8 ]
4-formyl-naphthalene-1-carboxylic acid [2-(4-chloro-phenyl)-ethyl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775

37
[ 4488-40-8 ]
4-[4-(4-chloro-benzyl)-piperazine-1-carbonyl]-naphthalene-1-carbaldehyde [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775

38
[ 4488-40-8 ]
4-[(3-chloro-4-hydroxybenzoyl)hydrazonomethyl]naphthoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775

39
[ 4488-40-8 ]
3-Chloro-4-hydroxy-benzoic acid [1-[4-(imidazole-1-carbonyl)-naphthalen-1-yl]-meth-(E)-ylidene]-hydrazide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775

40
[ 4488-40-8 ]
4-[(3-chloro-4-hydroxy-benzoyl)-hydrazonomethyl]-naphthalene-1-carboxylic acid diethylamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775

41
[ 4488-40-8 ]
4-[(3-chloro-4-hydroxy-benzoyl)-hydrazonomethyl]-naphthalene-1-carboxylic acid [2-(4-chloro-phenyl)-ethyl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775

42
[ 4488-40-8 ]
3-Chloro-4-hydroxy-benzoic acid [1-{4-[4-(4-chloro-benzyl)-piperazine-1-carbonyl]-naphthalen-1-yl}-meth-(E)-ylidene]-hydrazide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 5755 - 5775

44
[ 4488-40-8 ]
3-(4-methylnaphthoyl)-N-(2-(N-morpholino)ethyl)-2-methylindole [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 3094 - 3105
[2]Patent: WO2012/24670,2012,A2

45
[ 6627-78-7 ]
[ 4488-40-8 ]

Reference： [1]Journal of the American Chemical Society,1993,vol. 115,p. 2180 - 2190

46
[ 4488-40-8 ]
[ 71235-76-2 ]

Reference： [1]Journal of the American Chemical Society,1993,vol. 115,p. 2180 - 2190

47
[ 4488-40-8 ]
[ 123674-45-3 ]

Reference： [1]Journal of the American Chemical Society,1993,vol. 115,p. 2180 - 2190

48
[ 4488-40-8 ]
4-methyl-1-naphthylmethyl 9'-methyl-9'-fluorenecarboxylate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1993,vol. 115,p. 2180 - 2190

49
[ 4488-40-8 ]
[ 79797-78-7 ]

Reference： [1]Canadian Journal of Chemistry,1981,vol. 59,p. 2629 - 2641

50
[ 4488-40-8 ]
[ 41791-10-0 ]

Reference： [1]Canadian Journal of Chemistry,1981,vol. 59,p. 2629 - 2641

51
[ 90-12-0 ]
alkaline permanganate solution [ No CAS ]
[ 4488-40-8 ]

Reference： [1]Canadian Journal of Chemistry,1981,vol. 59,p. 2629 - 2641

52
[ 571-58-4 ]
[ 4488-40-8 ]

Reference： [1]Tetrahedron Letters,1984,vol. 25,p. 2139 - 2142

53
[ 49675-07-2 ]
[ 4488-40-8 ]

Reference： [1]Chemische Berichte,1951,vol. 84,p. 636,640

54
[ 5261-50-7 ]
[ 4488-40-8 ]

Reference： [1]Chemische Berichte,1951,vol. 84,p. 636,640
[2]Chemische Berichte,1951,vol. 84,p. 636,640

55
[ 4488-40-8 ]
[ 52823-48-0 ]

Reference： [1]Helvetica Chimica Acta,1974,vol. 57,p. 945 - 979

56
[ 4488-40-8 ]
[ 52823-45-7 ]

Reference： [1]Helvetica Chimica Acta,1974,vol. 57,p. 945 - 979

57
[ 4488-40-8 ]
[ 52823-46-8 ]

Reference： [1]Helvetica Chimica Acta,1974,vol. 57,p. 945 - 979

58
[ 4488-40-8 ]
[ 52823-47-9 ]

Reference： [1]Helvetica Chimica Acta,1974,vol. 57,p. 945 - 979

59
[ 67-56-1 ]
[ 4488-40-8 ]
[ 35615-98-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	With thionyl chloride; at 60℃;	To a solution of 4-methyl-1-naphthalenecarboxylic acid (4.14 g, 22.2 mmol) in methanol (50 ml) was added thionyl chloride (3 ml), and the mixture was stirred at 60C overnight. The reaction solution was concentrated, water (100 ml) was added and the mixture was extracted with ethyl acetate (100 ml×2). The extract was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure to give methyl 4-methyl-1-naphthalenecarboxylate (4.32 g, 97%) as a colorless oil. IR nu maxKBrcm-1: 1715, 1591.1H-NMR (CDCl3) delta: 2.75 (3H, s) , 3.99 (3H, s) , 7.35 (1H, d, J = 7.6 Hz), 7.50-7.68 (2H, m), 8.00-8.14 (2H, m), 8.92-9.02 (1H, m).
94.5%	With hydrogenchloride; at 0℃; for 16.0833h;Heating / reflux;	HCl was bubbled through a solution of 4-methyl-l -naphthoic acid (3.72 g, 20 mmol) in dry MeOH (200 ml) at 0 0C for 5 min. The resulting mixture was then refluxed for 16 h. Solvent was removed in vacuo and the residue dissolved in EtOAc and washed with NaOH (IN, 2 x 20 ml). The organic layer was then washed with water, brine, dried over MgSO4, filtered, and concentrated to afford methyl 4-methyl- 1-naphthalenecarboxylate (3.79 g, 94.5%) as an off white solid.
	With hydrogenchloride; at 0 - 20℃; for 19h;	Synthesis Example 17-1: Synthesis of methyl 4-methyl-1-naphthalene carboxylate (Compound III-2) 250.6 mg of commercially available 4-methyl-1-naphtalene carboxylate was dissolved in 7. 5 ml ofmethanol, followedby aerating with hydrogen chloride gas under ice-cold condition. After that, the mixture was stirred for 19 hours at room temperature and then the solvent was distilled off. The residue was dissolved in chloroform and was then washed with a 1 mol/l sodium hydroxide aqueous solution and dried with anhydrous sodium sulfate. Subsequently, the solvent was distilled off and dried under reduced pressure, and 269.9 mg of the above-mentioned compound was obtained as a colorless oily product. MS(FAB,Pos.):m/z=200[M+],201[M+1]+ 1H-NMR(500MHz,CDCl3):delta=2.73(3H,s),3.98(3H,s),7.33(1H,d,J=7.3H z),7.61(1H,d,J=8.5,6.8Hz),7.56(1H,dd,J=8.3,6.8Hz),8.04(1H,d,J =8.3Hz),8.08(1H,d,J=7.3Hz),8.97(1H,d,J=8.5Hz).

Reference： [1]Patent: EP1362846,2003,A1 .Location in patent: Page/Page column 64-65
[2]Patent: WO2008/124575,2008,A1 .Location in patent: Page/Page column 147
[3]Patent: EP1389460,2004,A1 .Location in patent: Page/Page column 42

60
[ 67-56-1 ]
[ 4488-40-8 ]
[ 2417-75-6 ]

Yield	Reaction Conditions	Operation in experiment
		Commercially available 4-methyl-1-naphthalene carboxylic acid (manufactured by Tokyo Kasei Kogyo Co., Ltd.) (251 mg) was dissolved in methanol (7.5 ml) and then aerated under ice-cooling with hydrogen chloride gas for 5 minutes. After that, the solution was stirred at room temperature for 19 hours and the solvent was then distilled off. The residue was dissolved in chloroform and then washed with a 1 mol/l sodium hydroxide aqueous solution. After the solution had been dried with anhydrous sodium sulfate, the solvent was then distilled off. The residue was dissolved in carbon tetrachloride (8.0 ml) and then added with N-bromo succinimide (253 mg) and azobisisobutyronitrile (22.1 mg), followed by stirring at 70C for 6 hours. After completion of the reaction, the solid was removed through glass filter, followed by concentration. The residue was dissolved in chloroform and then washed with a 1 mol/l sodium hydroxide aqueous solution and saturated saline solution. The solution was dried with anhydrous sodium sulfate and the solvent was then distilled off. The residue was dried under reduced pressure, thereby obtaining the subject compound (364 mg) as a pale-yellow oily substance. MS(FAB,Pos.):m/z=279,281[M+H]+ 1H-NMR(60MHz,CDCl3):delta=3.94(3H,s),4.86(3H,s),7.35-7.68(3H,m),7.88-8.21(2H,m),8.66-8.89(1H,m).

Reference： [1]Patent: EP1550657,2005,A1 .Location in patent: Page/Page column 55-56

61
[ 444912-95-2 ]
[ 4488-40-8 ]
N-(2-(4-fluorophenyl)-2-oxo-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-methyl-1-naphthalenecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With benzotriazol-1-ol; 1,8-diazabicyclo[5.4.0]undec-7-ene; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide);	To a solution of 1-(4-fluorophenyl)-1-oxo-3-(4-(trifluoromethyl)phenl)-2-propylamine hydrochloride (600 mg, 1.73 mmol) and 4-methyl-1-naphthalenecarboxylic acid (354 mg, 1.90 mmol) in N,N-dimethylformamide (10 ml) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. (496 mg, 2.59 mmol), 1-hydroxy-1H-benzotriazole (396 mg, 2.59 mmol) and 1,8-diazabicyclo[5.4.0]-7-undecene (0.28 ml, 1.90 mmol) and the mixture was stirred overnight. To the reaction solution were added 1N aqueous hydrochloric acid solution (10 ml) and water (100 ml), and the mixture was extracted with ethyl acetate (50 ml×2). The extract was washed with 1N aqueous sodium hydroxide solution and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1 and recrystallized from ethyl acetate-hexane to give N-(2-(4-fluorophenyl)-2-oxo-1-((4-(trifluoromethyl)phenyl)! methyl)ethyl)-4-methyl-1-naphthalenecarboxamide (665 mg, 80%). mp 149-150C IR nu maxKBrcm-1: 1693, 1634, 15.39, 1510. Anal. Calcd for C28H21F4NO2: C, 70.14; H, 4.41; N, 2.92 Found: C, 70.09; H, 4.42; N, 2.91.1H-NMR (CDCl3) delta: 2.71 (3H, s), 3.19 (1H, dd, J = 14.0, 6.2 Hz), 3.55 (1H, d, J = 14.0, 6.2 Hz), 6.16 (1H, q, J = 7.0 Hz), 6.83 (1H, d, J = 7.4 Hz), 7.14-7.32 (5H, m), 7.36-7.64 (5H, m), 7.98-8.18 (4H, m).

Reference： [1]Patent: EP1362846,2003,A1 .Location in patent: Page/Page column 32

62
(1RS,2SR)-2-amino-1-(4-fluorophenyl)-3-[4-(trifluoromethyl)phenyl]propan-1-ol [ No CAS ]
[ 4488-40-8 ]
N-((1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-methyl-1-naphthalenecarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In acetonitrile; at 20℃;	To a solution of (1R,2S)-2-amino-1-(4-fluorophenyl)-3-(4-(trifluoromethyl)phenyl)-1-propanol (450 mg, 1.44 mmol) in acetonitrile (30 ml) were added 4-methyl-1-naphthalenecarboxylic acid (268 mg, 1.44 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (413 mg, 2.15 mmol) and 1-hydroxy-1H-benzotriazole (220 mg, 1.44 mmol) and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:acetone=1.1) and recrystallized from ethyl acetate-hexane to give the title compound (487 mg, 70%). mp 198-199C IR nu maxKBrcm-1: 1636, 1620, 1607. Anal. Calcd for C28H23F4NO2: C, 69.85; H, 4.81; N, 2.91 Found: C, 69.80; H, 4.92; N, 2.79.1H-NMR (CDCl3)delta: 2.58 (3H, s), 2.66! -3.06 (1H, m), 3.33 (1H, brs), 4.60-4.80 (1H, m), 4.98-5.06 (1H, m), 5.80 (1H, d, J = 8.2 Hz), 6.92-7.54 (12H, m), 7.59 (1H, d, J = 8.6 Hz), 7.89 (1H, d, J = 8.2 Hz).

Reference： [1]Patent: EP1362846,2003,A1 .Location in patent: Page/Page column 51-52

63
[ 4488-40-8 ]
[ 35615-98-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In methanol; chloroform;	Example 17-1 Synthesis of methyl 4-methyl-1-naphthalene carboxylate (Compound III-2) Commercially available 4-methyl-1-naphthalenecarboxylic acid (250.6 mg) was dissolved in methanol (7.5 ml). Hydrogen chloride gas was blown into the solution for five minutes while cooling with ice. Then, the mixture was stirred for 19 hours at room temperature and the solvent was removed by distillation. The residue was dissolved in chloroform, washed with 1 mol/l aqueous solution of sodium hydroxide, and dried over anhydrous sodium sulfate. The solvent was removed by distillation. The residue was dried under reduced pressure to obtain the target compound (269.9 mg) as colorless oil. MS(FAB,Pos.):m/z=200[M+],201[M+1]+1H-NMR(500MHz,CDCl3):delta=2.73(3H,s),3.98(3H,s),7.33(1H,d,J= 7.3Hz),7.61(1H,dd,J=8.5,6.8Hz),7.56(1H,dd,J=8.3,6.8Hz),8.04 (1H,d,J=8.3Hz),8.08(1H,d,J=7.3Hz),8.97(1H,d,J=8.5Hz).

Reference： [1]Patent: EP1273571,2003,A1

64
[ 4488-40-8 ]
[ 100-51-6 ]
[ 1324000-37-4 ]

Reference： [1]Synthesis,2011,p. 1477 - 1483

65
[ 4488-40-8 ]
[ 75-65-0 ]
[ 1324000-26-1 ]

Reference： [1]Synthesis,2011,p. 1477 - 1483

66
[ 110-91-8 ]
[ 4488-40-8 ]
[ 1201581-76-1 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 20℃; for 12h;	EXAMPLE 6Preparation of morpholin-4-O-(4-{2-[-1-(9H-purin-6-yl)pyrrolidin-2-yl]ethyl}naphthalen-1-yl)methanone (?A6?)6.15 g of commercially available 4-methyl-1-naphthylic acid are reacted with 4.7 ml of morpholine, 5.2 g of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and 3.6 g of 1-hydroxybenzotriazole at RT for 12 h. Work-up and purification gives 5.4 g of brown oil (4-methylnaphthalen-1-yl)morphlin-4-ylmethanone; Rt.: 1.924 min; [M+H]+256.2.

Reference： [1]Patent: US2011/263561,2011,A1 .Location in patent: Page/Page column 17-18

67
[ 4488-40-8 ]
[ 1201581-77-2 ]

Reference： [1]Patent: US2011/263561,2011,A1

68
[ 4488-40-8 ]
[ 1201581-79-4 ]

Reference： [1]Patent: US2011/263561,2011,A1

69
[ 4488-40-8 ]
[ 1201581-78-3 ]

Reference： [1]Patent: US2011/263561,2011,A1

70
[ 4488-40-8 ]
[ 1349176-08-4 ]

Reference： [1]Heteroatom Chemistry,2011,vol. 22,p. 707 - 714

71
[ 4488-40-8 ]
[ 74-88-4 ]
[ 35615-98-6 ]

Yield	Reaction Conditions	Operation in experiment
99%		Preparation 50: 4-Methyl-naphthalene-1-carboxylic acid methyl ester To a stirred solution of 4-methyl-naphthalene-1-carboxylic acid (10 g, 53.70 mmol) in dry DMF (50 mL) was added potassium carbonate (11.14 g, 80.55 mmol) at room temperature. Resulting reaction mixture was stirred for 30 minutes at room temperature. Then reaction mixture was cooled to 0 C. and methyl iodide (11.44 g, 3.04 mL, 80.55 mmol) was added dropwise. Resulting reaction mixture was stirred for 3 hours at room temperature. Progress of reaction was monitored by TLC using 10% EtOAc in hexane. Rf of new spot and stating material was 0.7 and 0.1, respectively. After consumption of starting material, reaction mixture was quenched with ice cold water (150 mL) and extracted with EtOAc (2×150 mL). Combined organic layer was washed with water (300 mL), brine (200 mL) and dried over sodium sulphate. Organic layer was evaporated in vacuo to afford orange colored thick oil. Crude compound was purified by column chromatography using 100-200 mesh silica gel. Desired compound was eluted in 9% in EtOAc in hexane to afford colorless liquid (10.85 g, 99%). 1H NMR (400 MHz, CDCl3) delta: 2.73 (s, 3 H), 3.98 (S, 3H), 7.34 (d, J=7.4 Hz, 1H), 7.54-7.63 (m, 2H), 8.04 (d, J=7.92 Hz, 1H), 8.08 (d, J=7.44 Hz, 1H), 8.95 (d, J=8.12 Hz, 1H); LC-MS (m/z): =201.10 (M+H).

Reference： [1]Patent: US2012/77765,2012,A1 .Location in patent: Page/Page column 31

72
[ 4488-40-8 ]
[ 2417-75-6 ]