[ CAS No. 108-96-3 ] {[proInfo.proName]}

Name: 108-96-3|Pyridin-4(1H)-one|97%
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SKU: A107171
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2D 3D

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Quality Control of [ 108-96-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 108-96-3 ]

Product Details of [ 108-96-3 ]

CAS No. :	108-96-3	MDL No. :	MFCD00040458
Formula :	C₅H₅NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GCNTZFIIOFTKIY-UHFFFAOYSA-N
M.W :	95.10	Pubchem ID :	12290
Synonyms :

Calculated chemistry of [ 108-96-3 ]

Physicochemical Properties

Num. heavy atoms :	7
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	27.06
TPSA :	32.86 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.81 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.97
Log Po/w (XLOGP3) :	-1.31
Log Po/w (WLOGP) :	0.37
Log Po/w (MLOGP) :	-0.6
Log Po/w (SILICOS-IT) :	1.65
Consensus Log Po/w :	0.22

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.24
Solubility :	54.9 mg/ml ; 0.577 mol/l
Class :	Very soluble
Log S (Ali) :	1.12
Solubility :	1250.0 mg/ml ; 13.1 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	-1.84
Solubility :	1.36 mg/ml ; 0.0143 mol/l
Class :	Soluble

Medicinal Chemistry

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

Safety of [ 108-96-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 108-96-3 ]

* 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 [ 108-96-3 ]
Downstream synthetic route of [ 108-96-3 ]

[ 108-96-3 ] Synthesis Path-Upstream 1~10

1
[ 108-96-3 ]
[ 626-64-2 ]

Reference： [1] Journal of Organic Chemistry, 1980, vol. 45, # 8, p. 1354 - 1362
[2] Journal of Organic Chemistry USSR (English Translation), 1984, vol. 20, p. 1153 - 1158[3] Zhurnal Organicheskoi Khimii, 1984, vol. 20, # 6, p. 1268 - 1274
[4] Journal fuer Praktische Chemie (Leipzig), 1982, vol. 324, # 3, p. 369 - 378

2
[ 108-96-3 ]
[ 89282-03-1 ]
[ 7153-08-4 ]

Reference： [1] Archiv der Pharmazie (Weinheim, Germany), 1956, vol. 289, p. 651,660

3
[ 108-96-3 ]
[ 13626-17-0 ]

Reference： [1] Journal of Organic Chemistry, 2000, vol. 65, # 10, p. 3154 - 3159
[2] Journal of the American Chemical Society, 2012, vol. 134, # 22, p. 9390 - 9399
[3] Patent: WO2012/148808, 2012, A1,

4
[ 108-96-3 ]
[ 25813-25-6 ]

Reference： [1] Gazzetta Chimica Italiana, 1948, vol. 78, p. 873,876

5
[ 108-96-3 ]
[ 7153-08-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With N-iodo-succinimide In acetonitrile for 3 h; Reflux	I Oa. 3,5-Diiodo-pyridin-4-ol Into a 3 L three necked round bottom flask I ,4-dihydropyridin-4-one (50.0 g, 0.50 mol) and N-iodosuccinimide (232 g, 1.00 mmol) were suspended inacetonitrile (1 L). The reaction mixture was refluxed for 3h. The mixture was cooled down with an ice bath and then filtered and washed with acetonitrile (150 mL). The light yellow solid was dried at 60°C under reduced pressure for 15 hr to obtain 165 g (95 percent) of the title compound as a light yellow solid. LC/MS (Method B): Rt 1.34 mm, (M+H) 348.

Reference： [1] Patent: WO2015/144290, 2015, A1, . Location in patent: Page/Page column 69
[2] Journal of Medicinal Chemistry, 2016, vol. 59, # 3, p. 1078 - 1101
[3] DRP/DRBP Org.Chem., [4] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 20, p. 765
[5] Journal of the Society of Chemical Industry, London, 1943, vol. 62, p. 189
[6] Journal of the Society of Chemical Industry, London, 1946, vol. 65, p. 204
[7] Archiv der Pharmazie (Weinheim, Germany), 1956, vol. 289, p. 651,660
[8] Justus Liebigs Annalen der Chemie, 1932, vol. 494, p. 284,300

6
[ 108-96-3 ]
[ 89282-03-1 ]
[ 7153-08-4 ]

Reference： [1] Archiv der Pharmazie (Weinheim, Germany), 1956, vol. 289, p. 651,660

7
[ 108-96-3 ]
[ 5435-54-1 ]

Reference： [1] Patent: US6218539, 2001, B1,

8
[ 108-96-3 ]
[ 13091-23-1 ]
[ 5435-54-1 ]

Reference： [1] Journal of the Chemical Society, 1955, p. 2755,2761

9
[ 108-96-3 ]
[ 13091-23-1 ]

Reference： [1] Journal of the Chemical Society, 1955, p. 2755,2761

10
[ 108-96-3 ]
[ 15097-49-1 ]
[ 2456-81-7 ]

Reference： [1] Chemische Berichte, 1984, vol. 117, # 4, p. 1523 - 1541

[ 108-96-3 ] Synthesis Path-Downstream 1~81

1
[ 108-96-3 ]
[ 89282-03-1 ]
[ 7153-08-4 ]

Reference： [1]Archiv der Pharmazie,1956,vol. 289,p. 651,660

2
[ 108-96-3 ]
[ 25813-25-6 ]

Reference： [1]Gazzetta Chimica Italiana,1948,vol. 78,p. 873,876

3
[ 108-96-3 ]
[ 7153-08-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With N-iodo-succinimide; In acetonitrile; for 3h;Reflux;	I Oa. 3,5-Diiodo-pyridin-4-ol Into a 3 L three necked round bottom flask I ,4-dihydropyridin-4-one (50.0 g, 0.50 mol) and N-iodosuccinimide (232 g, 1.00 mmol) were suspended inacetonitrile (1 L). The reaction mixture was refluxed for 3h. The mixture was cooled down with an ice bath and then filtered and washed with acetonitrile (150 mL). The light yellow solid was dried at 60C under reduced pressure for 15 hr to obtain 165 g (95 %) of the title compound as a light yellow solid. LC/MS (Method B): Rt 1.34 mm, (M+H) 348.

Reference： [1]Patent: WO2015/144290,2015,A1 .Location in patent: Page/Page column 69
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 1078 - 1101
[3]DRP/DRBP Org.Chem.,
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 20,p. 765
[4]Journal of the Society of Chemical Industry,1943,vol. 62,p. 189
[5]Justus Liebigs Annalen der Chemie,1932,vol. 494,p. 284,300

4
[ 6974-32-9 ]
[ 108-96-3 ]
[ 18342-24-0 ]

Reference： [1]Chemische Berichte,1981,vol. 114,p. 1279 - 1286
[2]Journal of Organic Chemistry,2007,vol. 72,p. 173 - 179

5
[ 108-96-3 ]
[ 79-43-6 ]
[ 74669-37-7 ]

Reference： [1]Chemische Berichte,1980,vol. 113,p. 2086 - 2099

6
[ 108-96-3 ]
[ 103-82-2 ]
[ 74669-41-3 ]

Reference： [1]Chemische Berichte,1980,vol. 113,p. 2086 - 2099

7
[ 108-96-3 ]
[ 64-18-6 ]
[ 74885-83-9 ]

Reference： [1]Chemische Berichte,1980,vol. 113,p. 2110 - 2119

8
[ 108-96-3 ]
[ 15097-49-1 ]
[ 2456-81-7 ]

Reference： [1]Chemische Berichte,1984,vol. 117,p. 1523 - 1541

9
[ 108-96-3 ]
[ 42074-68-0 ]
[ 87839-58-5 ]

Reference： [1]Chemische Berichte,1983,vol. 116,p. 3011 - 3026

10
[ 108-96-3 ]
[ 76-83-5 ]
[ 87839-57-4 ]

Reference： [1]Chemische Berichte,1983,vol. 116,p. 3011 - 3026
[2]Journal of the Chemical Society. Perkin transactions I,1988,p. 1 - 8

11
[ 108-96-3 ]
[ 36725-28-7 ]
[ 113118-40-4 ]

Reference： [1]Journal of Organic Chemistry,1991,vol. 56,p. 1963 - 1966

12
[ 108-96-3 ]
[ 18162-48-6 ]
[ 616204-16-1 ]

Reference： [1]Journal of Organic Chemistry,1986,vol. 51,p. 1853 - 1855

13
[ 108-96-3 ]
[ 64-19-7 ]
[ 30074-98-7 ]

Reference： [1]Chemische Berichte,1980,vol. 113,p. 2086 - 2099

14
[ 108-96-3 ]
[ 802294-64-0 ]
[ 74669-29-7 ]

Reference： [1]Chemische Berichte,1980,vol. 113,p. 2086 - 2099

15
[ 108-96-3 ]
[ 621-82-9 ]
[ 74669-39-9 ]

Reference： [1]Chemische Berichte,1980,vol. 113,p. 2086 - 2099

16
[ 108-96-3 ]
[ 144863-34-3 ]
[ 155391-79-0 ]

Reference： [1]Tetrahedron,1994,vol. 50,p. 359 - 370

17
[ 108-96-3 ]
[ 624-83-9 ]
[ 83920-49-4 ]

Reference： [1]Tetrahedron Letters,1982,vol. 23,p. 3181 - 3184
[2]Synthesis,1983,p. 593 - 595
[3]Heterocycles,1984,vol. 21,p. 687

18
[ 108-96-3 ]
[ 78-95-5 ]
[ 153075-85-5 ]

Reference： [1]Journal of Antibiotics,1993,vol. 46,p. 1279 - 1288

19
[ 108-96-3 ]
[ 79-11-8 ]
[ 74669-35-5 ]

Reference： [1]Chemische Berichte,1980,vol. 113,p. 2086 - 2099

20
[ 108-96-3 ]
[ 88-95-9 ]
[ 74669-68-4 ]

Reference： [1]Chemische Berichte,1980,vol. 113,p. 2086 - 2099

21
[ 108-96-3 ]
[ 65-85-0 ]
[ 36228-61-2 ]

Reference： [1]Chemische Berichte,1980,vol. 113,p. 2086 - 2099

22
[ 108-96-3 ]
[ 74-86-2 ]
[ 27248-05-1 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1986,vol. 22,p. 2202 - 2204
Zhurnal Organicheskoi Khimii,1986,vol. 22,p. 2451 - 2454

23
[ 108-96-3 ]
[ 75-98-9 ]
[ 74669-45-7 ]

Reference： [1]Chemische Berichte,1980,vol. 113,p. 2086 - 2099

24
[ 108-96-3 ]
[ 88-65-3 ]
[ 74669-48-0 ]

Reference： [1]Chemische Berichte,1980,vol. 113,p. 2086 - 2099

25
[ 108-96-3 ]
[ 3881-38-7 ]

Reference： [1]Journal of Heterocyclic Chemistry,1984,vol. 21,p. 1277 - 1280
[2]Journal of the Chemical Society. Perkin transactions I,1988,p. 1 - 8
[3]Chemische Berichte,1930,vol. 63,p. 587,593

26
[ 108-96-3 ]
[ 28419-11-6 ]
[ 70149-39-2 ]

Reference： [1]Canadian Journal of Chemistry,1983,vol. 61,p. 2556 - 2562
[2]Canadian Journal of Chemistry,1983,vol. 61,p. 2556 - 2562

27
[ 108-96-3 ]
[ 17228-70-5 ]

Reference： [1]Journal of Organic Chemistry,1984,vol. 49,p. 4784 - 4786

28
[ 108-96-3 ]
[ 93111-35-4 ]

Reference： [1]Journal of Organic Chemistry,1984,vol. 49,p. 4784 - 4786

29
[ 5402-20-0 ]
[ 10026-13-8 ]
[ 108-96-3 ]
[ 626-61-9 ]
[ 3881-38-7 ]

Reference： [1]Journal of the Chemical Society,1939,p. 873,876

30
[ 108-96-3 ]
[ 28419-11-6 ]

Yield	Reaction Conditions	Operation in experiment
87%	With potassium hydroxide; bromine; In water; at 0℃; for 1h;	Step 1: 3,5-Dibromo-pyridin-4-one (10) To an ice-cooled solution of pyridine-4-one 9 (6.98 g, 73.4 mmol) and KOH (9.52 g, 146.8 mmol) in water (140 mL) was added bromine (7.58 mL, 147.5 mmol) dropwise over 30 min [Spivey, et al., J. Org. Chem. 65, 3154-3159 (2000)]. After an additional 30 min, the precipitate was filtered off, washed with a copious amount of water, and dried in vacuo. Yield 16.17 g (87%), yellow solid, mp 320 C. (sublimes). 1H NMR (DMSO-d6, 500 MHz): delta 12.3 (s, 1H), 8.26 (s, 2H). 13C NMR (DMSO-d6, 125 MHz): delta 167.5, 138.2, 138.2, 111.8, 111.8.
83%	With bromine; potassium hydroxide; In water; at 0℃; for 1.25h;	To a solution of 4-(1 H)-pyridone (0.95 g, 10 mmol) and potassium hydroxide (1.1 g, 20 mmol) in water (20 mL) cooled to 0 0C was added bromine (3.2 g, 20 mmol). After stirring at this temperature for 75 min, the mixture was filtered and the cake was washed with washed with cold water (3 x 50 mL) and hexane (3 x 20 mL) to furnish 3,5-dibromo-4- (1 /-/)-pyridone as a white solid (2.09 g, 83%).
35%	With hydrogen bromide; bromine; at 0 - 20℃; for 1.5h;Inert atmosphere; Schlenk technique;	A solution of pyridin-4(1H)-one (2 g, 21.03 mmols) in 48% hydrobromic acid (23 ml) was cooled to 0 C and bromine (2.37 ml, 46.27 mmols) was added. The mixture was brought to rt and stirred for 1.5 h. After addition of water (60 mL) and a further 30 min of stirring, the precipitated solid was filtered off, washed with small portions of water and then dried in in vacuo. The product (1.85 g, 7.3 mmols, 35%) was obtained as a colorless solid. Rf: 0.65 (15% MeOH/DCM). 1H-NMR (500 MHz, DMSO-d6) delta = 12.26 (s, 1H), 8.24 (s, 2H). 13C-NMR (126 MHz, DMSO-d6) delta = 167.49, 138.18, 111.80. ESI-MS: m/z = 254.14 [M+H]+. HRMS (ESI): calculated for C5H4ON 79Br2: m/z = 251.86542 [M+H]+, found: m/z = 251.86557 [M+H]+. calculated for C5H4ON 79Br 81Br: m/z = 253.86337 [M+H]+, found: m/z = 253.86284 [M+H]+. calculated for C5H4ON 81Br2: m/z = 255.86132 [M+H]+, found: m/z = 255.86030 [M+H]+.

	With potassium hydroxide; bromine; In water;	3,5-Dibromo-<strong>[108-96-3]4-pyridone</strong> (VIII, W=Br) The dibromination of <strong>[108-96-3]4-pyridone</strong> was carried out according to a modified known method (O. S. Tee et al. Can. J. Chem. 1983, 61, 2556). Thus, to an ice-cooled and mechanically stirred solution of <strong>[108-96-3]4-pyridone</strong> (34.9 g, 0.367 mol) and KOH (41.2 g, 0.736 mol) in water (700 mL) was added Br2 (37.9 mL, 0.735 mol) dropwise over 30 min. After additional 30 min, the white precipitate was filtered off, washed with a copious amount of water, and dried in vacuo to give the crude 3,5-dibromo-<strong>[108-96-3]4-pyridone</strong> (VIII, W=Br) (79.0 g, 85%) which was used in the next step without further purification.
	With bromine; potassium hydroxide; In water; at 0 - 5℃; for 2h;	To an ice-cooled solution of pyridine-4-one 9 (2 g, 21.03 mmol) and potassium hydroxide (2.35 g, 42 mmol) in water (40 mL) was added bromine (7.58 mL, 147.5 mmol) drop wise. The reaction mixture was stirred for 2 h at 0-5 C The precipitate was filtered off, washed with a copious amount of water and then hexane, dried in vacuum to obtain the title compound. MS (M+l): 253.8.

Reference： [1]Patent: US2008/20010,2008,A1 .Location in patent: Page/Page column 16
[2]Journal of Organic Chemistry,2000,vol. 65,p. 3154 - 3159
[3]Patent: WO2010/41054,2010,A1 .Location in patent: Page/Page column 38
[4]Tetrahedron,2010,vol. 66,p. 2398 - 2403
[5]Tetrahedron,2018,vol. 74,p. 4531 - 4537
[6]Patent: US2003/17942,2003,A1
[7]Journal of the American Chemical Society,2012,vol. 134,p. 9390 - 9399
[8]Patent: WO2012/148808,2012,A1 .Location in patent: Page/Page column 56; 57

31
[ 108-96-3 ]
[ 602-09-5 ]
[1,1']binaphthalenyl-2,2'-diol; compound with 1<i>H</i>-pyridin-4-one [ No CAS ]

Reference： [1]Heterocycles,2003,vol. 59,p. 735 - 744

32
[ 221163-57-1 ]
[ 108-96-3 ]
[ 221163-60-6 ]

Yield	Reaction Conditions	Operation in experiment
31%	In tetrahydrofuran; at 90 - 100℃; for 22h;	To a solution of the compound in Example 9 (180 mg, 610 mumol) in tetrahydrofuran (20 ml) was added <strong>[108-96-3]4-pyridone</strong> (290 mg, 3.05 mmol), followed by tube sealing, and the mixture was stirred for 4 hours at 100 C. and for 18 hours at 90 C. After cooling, the reaction mixture was concentrated under reduced pressure and the residue obtained was purified by means of silica gel column chromatography [chloroform:ethanol=40:1?20:1] to obtain 70.0 mg of the title compound as a pale yellow liquid. Yield 31%. 1H-NMR(CDCl3,delta):1.47(3H,t,J=7.2 Hz),4.24(3H,s),4.56(2H,q,J=7.2 Hz),6.52(2H,d,J=7.8 Hz),7.38(2H,d,J=7.8 Hz),8.22(1H,s), 8.60(1H,s).

Reference： [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 5841 - 5863
[2]Patent: US6348461,2002,B1 .Location in patent: Page column 40

33
[ 108-96-3 ]
[ 24424-99-5 ]
[ 332940-69-9 ]

Reference： [1]Organic letters,2001,vol. 3,p. 711 - 714
[2]Journal of Organic Chemistry,2009,vol. 74,p. 3843 - 3848

34
[ 77070-79-2 ]
[ 108-96-3 ]

Reference： [1]Russian Journal of Organic Chemistry,2005,vol. 41,p. 1113 - 1115

35
[ 694-54-2 ]
[ 108-96-3 ]
[ 870150-51-9 ]

Reference： [1]Synlett,2005,p. 2808 - 2810

36
[ 108-96-3 ]
[ 15590-90-6 ]
[ 19872-96-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; nitric acid
	With sulfuric acid; nitric acid at -5 - 130℃; for 96h; Inert atmosphere;

Reference： [1]Morak, Beata; Pluta, Krystian; Suwinska, Kinga; Grymel, Miroslawa; Besnard, Celine; Schiltz, Marc; Kloc, Christian; Siegrist, Theo [Heterocycles, 2005, vol. 65, # 11, p. 2619 - 2634]
[2]De Rycke, Nicolas; Berionni, Guillaume; Couty, Francois; Mayr, Herbert; Goumont, Regis; David, Olivier R. P. [Organic Letters, 2011, vol. 13, # 3, p. 530 - 533]

37
[ 108-96-3 ]
[ 14958-40-8 ]
C₂₈H₄₇OC₅H₄NO [ No CAS ]

Reference： [1]Mendeleev Communications,2007,vol. 17,p. 281 - 283

38
[ 108-96-3 ]
[ 871-84-1 ]
C₁₃H₁₅NO [ No CAS ]

Reference： [1]Chemistry - A European Journal,2007,vol. 13,p. 7443 - 7465

39
[ 108-96-3 ]
[ 871-84-1 ]
C₁₃H₁₅NO [ No CAS ]

Reference： [1]Chemistry - A European Journal,2007,vol. 13,p. 7443 - 7465

40
[ 108-96-3 ]
[ 13626-17-0 ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 3154 - 3159
[2]Journal of the American Chemical Society,2012,vol. 134,p. 9390 - 9399
[3]Patent: WO2012/148808,2012,A1

41
[ 108-96-3 ]
diethyl-[3-(3-methoxy-phenyl)-pyridin-4-yl]-amine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 3154 - 3159

42
[ 108-96-3 ]
diethyl-(3-naphthalen-1-yl-pyridin-4-yl)-amine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 3154 - 3159

43
[ 108-96-3 ]
[ 278600-42-3 ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 3154 - 3159
[2]Journal of the American Chemical Society,2012,vol. 134,p. 9390 - 9399

44
[ 108-96-3 ]
[ 278600-44-5 ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 3154 - 3159

45
[ 108-96-3 ]
[ 278600-41-2 ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 3154 - 3159
[2]Journal of the American Chemical Society,2012,vol. 134,p. 9390 - 9399

46
[ 108-96-3 ]
[ 278600-43-4 ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 3154 - 3159
[2]Journal of the American Chemical Society,2012,vol. 134,p. 9390 - 9399

47
[ 108-96-3 ]
(+)-diethyl[3-(2-phenylnaphthyl)(4-pyridyl)]amine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 3154 - 3159

48
[ 108-96-3 ]
(-)-diethyl[3-(2-phenylnaphthyl)(4-pyridyl)]amine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 3154 - 3159

49
[ 108-96-3 ]
[ 65018-90-8 ]
[ 123596-39-4 ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; ethyl acetate;	EXAMPLE 3 6-Cyano-2,2-dimethyl-4-(4(1H)-pyridon-1-yl)-2H-1-benzopyran STR11 Potassium t-butoxide (0.282 g, 2.52 mmol) was added to a stirred solution of 6-cyano-3,4-dihydro-2,2-dimethyl-3,4-epoxy-2H-1-benzopyran (0.506 g, 2.52 mmol) and <strong>[108-96-3]4-pyridone</strong> (0.239 g, 2.52 mmol) in dry dimethyl sulphoxide (5 ml) under nitrogen at ambient temperature. The reaction mixture was allowed to stir for 7 days then poured into water and the aqueous layer extracted with ethyl acetate (3) and chloroform (3). The organic layers were washed with water, combined, dried, filtered and evaporated to give a yellow oil which was chromatographed on silica. Elution with methanol: chloroform (3:97) gave an oil which was re-chromatographed on alumina. Elution with chloroform gave an oil (0.372 g) consisting of the title compound contaminated with dimethyl sulphoxide. The oil was taken up in ethyl acetate, washed with water (*3), dried, filtered and evaporated to an oil (0.080 g) which was triturated with ether and filtered to give 6-cyano-2,2-dimethyl-4-(4(1 H)-pyridon-1-yl)-2H-1-benzopyran, (0.041 g), (6%), m.p. 198-203 C. 1 H nmr (CDCl3) delta:1.58 (6H, s), 5.84 (1H,s), 6.48 (2H, d, J=7.7 Hz), 6.99 (1H, d, J=8.2 Hz), 7.13 (1H, d, J=1.9 Hz), 7.30 (2H, d, J=7.7 Hz), 7.55 (1H, dd, J=1.9 and 8.2 Hz). Anal: Found C, 72.80; H, 5.62; N, 9.80%; C17 H14 N2 O2 requires C, 73.36; H 5.07; N 10.07%.

Reference： [1]Patent: US5254557,1993,A

50
[ 108-96-3 ]
[7-(2-Chloro-ethoxy)-6-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-phenyl)-amine Hydrochloride [ No CAS ]
1-{2-[4-(3-Ethynyl-phenylamino)-6-(2-methoxy-ethoxy)-quinazolin-7-yloxy]-ethyl}-1H-pyridin-4-one hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With NaH; tetra-(n-butyl)ammonium iodide; In methanol; N,N-dimethyl-formamide; mineral oil;	EXAMPLE 50 1-{2-[4-(3-Ethynyl-phenylamino)-6-(2-methoxy-ethoxy)-quinazolin-7-yloxy]-ethyl}-1H-pyridin-4-one Hydrochloride NaH (30 mg of 60% in mineral oil, 0.77 mmol) was added to anhydrous DMF (2.0 mL) followed by pyrid-4-one (79 mg, 0.83 mmol). The mixture was stirred 40 minutes at 22 C. until all solids dissolved and the evolution of H2 ceased. The title product of Example 34 (120 mg, 0.28 mmol) and tetrabutylammonium iodide (15 mg) were added and the reaction mixture was stirred at 22 C. for 7 days under N2. Additional pyrid-4-one (79 mg) and NaH (30 mg of 60%) were dissolved in DMF (2 mL) and the solution was added to the reaction mixture. After another 4 days stirring the mixture was partitioned between CHCl3 and brine. The organic extracts were dried over Na2 SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica utilizing 10% methanol/CH2 Cl2 to afford 65 mg of the free base of the title product which was converted to the mono-hydrochloride salt according to the procedure described for Example 28 (66 mg; M.P. 240-248 C. (dec); LC-MS: 457 (MH+); anal. RP-HPLC RT: 3.23 min)
	With NaH; tetra-(n-butyl)ammonium iodide; In methanol; N,N-dimethyl-formamide; mineral oil;	EXAMPLE 50 1-{2-[4-(3-Ethynyl-phenylamino)-6-(2-methoxy-ethoxy)-quinazolin-7-yloxy]-ethyl}-1H-pyridin-4-one hydrochloride NaH (30 mg of 60% in mineral oil, 0.77 mmol) was added to anhydrous DMF (2.0 mL) followed by pyrid-4-one (79 mg, 0.83 mmol). The mixture was stirred 40 minutes at 22C until all solids dissolved and the evolution of H2ceased. The title product of Example 34 (120 mg, 0.28 mmol) and tetrabutylammonium iodide (15 mg) were added and the reaction mixture was stirred at 22C for 7 days under N2. Additional pyrid-4-one (79 mg) and NaH (30 mg of 60%) were dissolved in DMF (2 mL) and the solution was added to the reaction mixture. After another 4 days stirring the mixture was partitioned between CHCl3and brine. The organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica utilizing 10% methanol/ CH2Cl2to afford 65 mg of the free base of the title product which was converted to the mono-hydrochloride salt according to the procedure described for Exainple 28 (66 mg; M.P. 240-248C (dec); LC-MS: 457 (MH+); anal. RP-HPLC RT: 3.23 min)

Reference： [1]Patent: US5747498,1998,A
[2]Patent: EP1110953,2001,A1

51
[ 108-96-3 ]
[ 821777-58-6 ]
4-[[2-(4-pyridinyloxy)ethyl](2,2,2-trifluoroethyl)amino]-2-(trifluoromethyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 45; 4-[[2-(4-Pyridinyloxy)ethyl](2,2,2-trifluoroethyl)amino]-2- (trifluoromethyl)benzonitrile; Synthesized as described in Example 1C from 4-[(2-hydroxyethyl)(2,2,2- trifluoroethyl)amino]-2-(trifluoromethyl)benzonitrile and <strong>[108-96-3]4-pyridone</strong>, using dry DME as reaction solvent: 1H NMR (400 MHz, CDCI3) delta 8.45 (dd, J = 5.0, 1.3 Hz, 2H), 7.68 (d, J = 8.8 Hz, 1 H), 7.18 (d, J = 2.5 Hz, 1 H), 7.01 (dd, J = 8.7, 2.6 Hz, 1 H), 6.77 (dd, J = 4.9, 1.3 Hz, 2H), 4.27 (t, J = 5.2 Hz, 2H), 4.19 (q, J = 8.5 Hz, 2H), 4.04 (t, J = 5.3 Hz, 2H).

Reference： [1]Patent: WO2006/44707,2006,A1 .Location in patent: Page/Page column 66-67

52
[ 108-96-3 ]
P₂ S₅ [ No CAS ]
[ 7285-11-2 ]
[ 101234-67-7 ]
1-(1-Diphenylmethoxycarbonyl-1-ethyl)-4-thiopyridone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	In pyridine; chloroform;	REFERENCE EXAMPLE 10 1-(1-Diphenylmethoxycarbonyl-1-ethyl)-4-thiopyridone 2.31 g of <strong>[108-96-3]4-pyridone</strong> synthesised in a manner similar to that in Reference Example 8 was dissolved in 23 ml of pyridine, 1.55 g of P2 S5 was added, and reacted at 90 C. for an hour. After the reaction, the solvent was removed, chloroform was added, the pH was adjusted to 7.8 with NaHCO3, the mixture was washed with water, and dried over magnesium sulfate. The solvent was removed, and the residue was purified on silica gel column chromatography using chloroform-methanol (20:1) to obtain 1.38 g of the title compound (57%). IR (Nujor) nucm-1: 1754. NMR (DMSO-d6) delta: 1.70 (3H d J=6), 4.65 (1H q J=6), 6.85 (1H S), 7.10 (2H d J=6), 7.30 (10H S), 7.55 (2H d J=6).

Reference： [1]Patent: US4785090,1988,A

53
[ 108-96-3 ]
[ 67-56-1 ]
[ 7664-93-9 ]
[ 13556-71-3 ]

Yield	Reaction Conditions	Operation in experiment
	With p-toluenesulfonic acid monohydrate; In CH2 Cl4; benzylamine;	EXAMPLE 5 4-Benzylaminopyridine Under agitation, 0.38 g. (2 mmol) of p-toluenesulfonic acid hydrate was added to a suspension of 1.9 g. (20 mmol) of <strong>[108-96-3]4-pyridone</strong> and 4.39 g. (15 mmol) of octamethylcyclotetrasilazane in 8.75 ml. (80 mmol) of benzylamine; the solution foamed during this step. After gentle heating, the temperature of the mixture was elevated to 200 C. for 15 hours and, after cooling, the mixture was briefly boiled with 120 ml. of CH3 OH. After evaporation, the mixture was dissolved in 100 ml. of CH2 Cl4. The bases were extracted 3 times with 40 ml. of icecold 2 N H2 SO4. pH was brought to 9 by adding ice-cold, concentrated NaOH. Extraction of the turbid alkaline solution with 4 times 75 ml. of ether, drying (Na2 SO4), and carbon treatment yielded, upon evaporation, 3.9 g. of a crude product which produced from 200 ml. of hexane by cooling and concentration in three portions a total of 2.81 g. (76.35%) of 4-benzylaminopyridine, m.p. 108-110 C.

Reference： [1]Patent: US4169943,1979,A

54
[ 108-96-3 ]
[ 7285-11-2 ]
[ 101234-67-7 ]
1-(1-Diphenylmethoxycarbonyl-1-ethyl)-4-thiopyridone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With P2S5; In pyridine; chloroform;	Reference Example 10 1-(1-Diphenylmethoxycarbonyl-1-ethyl)-4-thiopyridone 2.31 g of <strong>[108-96-3]4-pyridone</strong> synthesised in a manner similar to that in Reference Example 8 was dissolved in 23 ml of pyridine, 1.55 g of P2S5 was added, and reacted at 90oC for an hour. After the reaction, the solvent was removed, chloroform was added, the pH was adjusted to 7.8 with NaHCO3, the mixture was washed with water, and dried over magnesium sulfate. The solvent was removed, and the residue was purified on silica gel column chromatography using chloroform -methanol (20:1) to obtain 1.38 g of the title compund (57%). IR (Nujor) gammacmmin1: 1754. NMR (DMSO-d6) delta: 1.70 (3H d J=6), 4.65 (1H q J=6), 6.85 (1H S), 7.10 (2H d J=6), 7.30 (10H S), 7.55 (2H d J=6).

Reference： [1]Patent: EP153709,1991,B1

55
[ 108-96-3 ]
[ 5435-54-1 ]

Yield	Reaction Conditions	Operation in experiment
	In (2S)-N-methyl-1-phenylpropan-2-amine hydrate;	a) Preparation of 4-hydroxy-3-nitropyridine 4-Hydroxy-3-nitropyridine was prepared by addition of <strong>[108-96-3]4-pyridone</strong> (50 g, 0.532M) to a mixture of fuming nitric acid and sulfuric acid. The resulting solution was heated for 1 hour at 100 C. The solution was cooled and poured into 500 mL of ice water and the desired product was obtained as a solid. (mp. 280 C.)

Reference： [1]Patent: US6218539,2001,B1

56
[ 865434-80-6 ]
[ 108-96-3 ]
[ 1025505-24-1 ]
[ 1025504-30-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 2329 - 2366
[2]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 2329 - 2366

57
[ 865434-79-3 ]
[ 108-96-3 ]
[ 1025504-29-3 ]
[ 1025504-28-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 2329 - 2366
[2]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 2329 - 2366

58
[ 108-96-3 ]
[ 541-41-3 ]
[ 57330-83-3 ]

Reference： [1]Journal of Organic Chemistry,2009,vol. 74,p. 3843 - 3848

59
[ 108-96-3 ]
[ 19872-96-9 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 1994 - 2005

60
[ 108-96-3 ]
[ 1225059-25-5 ]
[ 1225059-91-5 ]

Yield	Reaction Conditions	Operation in experiment
30%	With caesium carbonate;copper; In 1-methyl-pyrrolidin-2-one; at 150℃; for 1h;	Example 10 : l-(5-amino-6-(6-methyl-lH-benzo[dlimidazol-2-yl)pyrazin-2-yl)pyridin-4(lH)- one (Compound 1-24)SCHEME XMethod A Steps 1 -3 Compound 1-24Compound 1-24 was prepared using Method A, Steps 1-3 followed by Method J, Step 1. METHOD J : l-(5-amino-6-(6-methyl-lH-benzo[d]imidazol-2-yl)pyrazin-2-yl)pyridin- 4(lH)-one[00294] A mixture of 5-bromo-3-(6-methyl-lH-benzimidazol-2-yl)pyrazin-2-amine (80 mg, 0.263mmol), pyridin-4(lH)-one (287mg, 2.63mmol), cesium carbonate (257mg, 0.8mmol) and copper (5mg, 0.08mmol) were heated in NMP (2 mL) at 15O0C for 1 hour. The reaction mixture was diluted with EtOAc, washed with IN NaOH, and the organic layer filtered through a pad of celite and concentrated in vacuo. The resulting solid was purified by reverse phase preparative HPLC [Waters Sunfire C 18, lOuM, IOOA column, gradient 10% - 95%B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25mL/min]. The fractions were collected and freeze-dried to give the title compound (24.7mg, 30% Yield).IH NMR (400.0MHz, MeOD) d 2.5 (3H,s), 6.65 (2H,d), 7.1-7.2 (lH,m), 7.4-7.5 (lH,m), 7.5- 7.6 (lH,m), 8.45 (lH,s), 8.6 (2H,d) ppm; MS (ES+) 319

Reference： [1]Patent: WO2010/54398,2010,A1 .Location in patent: Page/Page column 107-108

61
[ 108-96-3 ]
[ 869638-44-8 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 15380 - 15389

62
[ 694-59-7 ]
[ 108-96-3 ]
[ 76520-27-9 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 1840 - 1843

63
[ 108-96-3 ]
[ 3140-73-6 ]
[ 1432754-92-1 ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 5078 - 5084

64
[ 108-96-3 ]
[ 536-74-3 ]
[ 63731-38-4 ]

Yield	Reaction Conditions	Operation in experiment
		I2 was added to an aqueous solution of pyridin-4-ol 21 (5.0 g, 52.6 mmol) and NaOH (2.7 g,67.5 mmol). The mixture was stirred at room temperature (2 h). Then, the solid was filtered and recrystalized in H2O to obtain a white solid. Then,following the Sakamoto?s procedure [7], the expected furo[3,2-c]pyridine 22 was obtained: 1H NMR(CDCl3) d 7.08 (s, H3), 7.40-7.52 (m, H4, 3 C6H5), 7.89 (d, J = 7.2 Hz, C6H5ortho), 8.44-8.54 (br s, Hpyridine), 8.87-8.99 (br s, Hpyridine); 13C NMR (CDCl3) d 99.1, 107.0, 125.3, 129.0, 129.4, 129.5, 144.0, 144.5, 156.9, 159.2.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 81,p. 181 - 191

65
[ 108-96-3 ]
3CF₃O₃S^(1-)*C₁₅H₂₁N₆P₂⁽³⁺⁾ [ No CAS ]
C₁₀H₁₁N₃*CHF₃O₃S [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2014,vol. 2014,p. 7631 - 7642

66
[ 108-96-3 ]
[ 141699-55-0 ]
1,1-dimethylethyl 3-(4'-pyridinyloxy)-1-azetidinecarboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2015,vol. 54,p. 5662 - 5665
Angew. Chem.,2015,vol. 126,p. 5754 - 5757,4
Angewandte Chemie,2015,vol. 126,p. 5754 - 5757,4

67
[ 108-96-3 ]
[ 60857-50-3 ]
1-(6-chlorohex-1-en-3-yl)pyridin-4(1H)-one [ No CAS ]