[ CAS No. 34133-58-9 ] {[proInfo.proName]}

Name: 34133-58-9|4-Hydroxyisophthalonitrile|98%
Brand: Ambeed
SKU: A114177
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Quality Control of [ 34133-58-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 34133-58-9 ]

Product Details of [ 34133-58-9 ]

CAS No. :	34133-58-9	MDL No. :	MFCD11870755
Formula :	C₈H₄N₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QESYLFCJDFCRIT-UHFFFAOYSA-N
M.W :	144.13	Pubchem ID :	12325963
Synonyms :

Calculated chemistry of [ 34133-58-9 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	37.89
TPSA :	67.81 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-6.23 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.15
Log Po/w (XLOGP3) :	1.33
Log Po/w (WLOGP) :	1.14
Log Po/w (MLOGP) :	0.15
Log Po/w (SILICOS-IT) :	1.29
Consensus Log Po/w :	1.01

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.98
Solubility :	1.53 mg/ml ; 0.0106 mol/l
Class :	Very soluble
Log S (Ali) :	-2.36
Solubility :	0.636 mg/ml ; 0.00441 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.97
Solubility :	1.54 mg/ml ; 0.0107 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.37

Safety of [ 34133-58-9 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 34133-58-9 ]

* 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 [ 34133-58-9 ]
Downstream synthetic route of [ 34133-58-9 ]

[ 34133-58-9 ] Synthesis Path-Upstream 1~22

1
[ 615-58-7 ]
[ 34133-58-9 ]

Reference： [1] Patent: WO2011/141933, 2011, A2, . Location in patent: Page/Page column 43-44

2
[ 22433-92-7 ]
[ 34133-58-9 ]

Reference： [1] Patent: WO2006/135316, 2006, A1, . Location in patent: Page/Page column 62

3
[ 619-72-7 ]
[ 34133-58-9 ]

Reference： [1] Patent: WO2011/130383, 2011, A1, . Location in patent: Page/Page column 95

4
[ 615-58-7 ]
[ 34133-58-9 ]

Reference： [1] Patent: WO2011/141933, 2011, A2, . Location in patent: Page/Page column 43

5
[ 4387-30-8 ]
[ 34133-58-9 ]
[ 143057-10-7 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1992, # 7, p. 1831 - 1851

6
[ 151-50-8 ]
[ 619-72-7 ]
[ 13520-07-5 ]
[ 34133-58-9 ]
[ 134165-33-6 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1991, # 4, p. 738 - 762

7
[ 619-72-7 ]
[ 34133-58-9 ]
[ 636-46-4 ]

Reference： [1] Patent: US3933807, 1976, A,

8
[ 52054-41-8 ]
[ 34133-58-9 ]
[ 4387-30-8 ]
[ 143057-10-7 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1992, # 7, p. 1831 - 1851
[2] Journal of Chemical Research, Miniprint, 1992, # 7, p. 1831 - 1851

9
[ 94353-39-6 ]
[ 34133-58-9 ]

Reference： [1] Helvetica Chimica Acta, 1984, vol. 67, p. 1580 - 1587

10
[ 151-50-8 ]
[ 619-72-7 ]
[ 34133-58-9 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1991, # 4, p. 738 - 762

11
[ 52054-41-8 ]
[ 62-53-3 ]
[ 34133-58-9 ]
[ 118412-92-3 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1990, # 7, p. 1662 - 1681

12
[ 151-50-8 ]
[ 619-72-7 ]
[ 34133-58-9 ]
[ 19619-22-8 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1991, # 4, p. 738 - 762
[2] Journal of Chemical Research, Miniprint, 1991, # 4, p. 738 - 762

13
[ 615-58-7 ]
[ 34133-58-9 ]

Reference： [1] Helvetica Chimica Acta, 1984, vol. 67, p. 1580 - 1587

14
[ 36914-79-1 ]
[ 34133-58-9 ]

Reference： [1] Helvetica Chimica Acta, 1984, vol. 67, p. 1580 - 1587

15
[ 2976-30-9 ]
[ 151-50-8 ]
[ 34133-58-9 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1991, # 4, p. 738 - 762

16
[ 52054-41-8 ]
[ 34133-58-9 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1992, # 7, p. 1831 - 1851

17
[ 67-56-1 ]
[ 151-50-8 ]
[ 619-72-7 ]
[ 34133-58-9 ]
[ 22433-92-7 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1991, # 4, p. 738 - 762

18
[ 52054-41-8 ]
[ 34133-58-9 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1990, # 7, p. 1662 - 1681

19
[ 52054-41-8 ]
[ 1885-29-6 ]
[ 34133-58-9 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1990, # 7, p. 1662 - 1681

20
[ 52054-41-8 ]
[ 34133-58-9 ]
[ 143057-10-7 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1992, # 7, p. 1831 - 1851

21
[ 52054-41-8 ]
[ 34133-58-9 ]
[ 34633-31-3 ]
[ 143057-10-7 ]

Reference： [1] Journal of Chemical Research, Miniprint, 1992, # 7, p. 1831 - 1851

22
[ 615-58-7 ]
[ 544-92-3 ]
[ 34133-58-9 ]

Reference： [1] Molecular crystals and liquid crystals, 1983, vol. 82, # 10, p. 331 - 338

[ 34133-58-9 ] Synthesis Path-Downstream 1~88

1
[ 615-58-7 ]
[ 544-92-3 ]
[ 34133-58-9 ]

Reference： [1]Molecular Crystals and Liquid Crystals (1969-1991),1983,vol. 82,p. 331 - 338

2
[ 2976-30-9 ]
[ 151-50-8 ]
[ 34133-58-9 ]
2-Hydroxy-5-methanesulfonyl-benzonitrile [ No CAS ]

Reference： [1]Journal of Chemical Research, Miniprint,1991,p. 738 - 762

3
[ 34133-58-9 ]
[ 73152-73-5 ]
4-Pentyl-bicyclo[2.2.2]octane-1-carboxylic acid 2,4-dicyano-phenyl ester [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1984,vol. 67,p. 1580 - 1587

4
[ 34133-58-9 ]
[ 34633-30-2 ]

Reference： [1]Journal of Chemical Research, Miniprint,1992,p. 1831 - 1851

5
[ 34133-58-9 ]
[ 34633-31-3 ]

Reference： [1]Journal of Chemical Research, Miniprint,1992,p. 1831 - 1851

6
[ 4387-30-8 ]
[ 34133-58-9 ]
[ 143057-10-7 ]

Reference： [1]Journal of Chemical Research, Miniprint,1992,p. 1831 - 1851

7
[ 52054-41-8 ]
[ 34133-58-9 ]
[ 34633-31-3 ]
[ 143057-10-7 ]

Reference： [1]Journal of Chemical Research, Miniprint,1992,p. 1831 - 1851

8
[ 52054-41-8 ]
[ 34133-58-9 ]
[ 4387-30-8 ]
[ 143057-10-7 ]

Reference： [1]Journal of Chemical Research, Miniprint,1992,p. 1831 - 1851
[2]Journal of Chemical Research, Miniprint,1992,p. 1831 - 1851

9
[ 52054-41-8 ]
[ 34133-58-9 ]
4-(2-Cyano-phenylamino)-isophthalonitrile [ No CAS ]
5-(2-Cyano-phenylamino)-2-nitro-isophthalonitrile [ No CAS ]

Reference： [1]Journal of Chemical Research, Miniprint,1990,p. 1662 - 1681

10
[ 52054-41-8 ]
[ 34133-58-9 ]
[ 143057-10-7 ]

Reference： [1]Journal of Chemical Research, Miniprint,1992,p. 1831 - 1851

11
[ 52054-41-8 ]
[ 62-53-3 ]
[ 34133-58-9 ]
[ 118412-92-3 ]

Reference： [1]Journal of Chemical Research, Miniprint,1990,p. 1662 - 1681

12
[ 94353-39-6 ]
[ 34133-58-9 ]

Reference： [1]Helvetica Chimica Acta,1984,vol. 67,p. 1580 - 1587

13
[ 52054-41-8 ]
[ 1885-29-6 ]
[ 34133-58-9 ]
4-(2-Cyano-phenylamino)-isophthalonitrile [ No CAS ]
5-(2-Cyano-phenylamino)-2-nitro-isophthalonitrile [ No CAS ]

Reference： [1]Journal of Chemical Research, Miniprint,1990,p. 1662 - 1681

14
[ 67-56-1 ]
[ 151-50-8 ]
[ 619-72-7 ]
[ 34133-58-9 ]
[ 22433-92-7 ]

Reference： [1]Journal of Chemical Research, Miniprint,1991,p. 738 - 762

15
[ 151-50-8 ]
[ 619-72-7 ]
[ 13520-07-5 ]
[ 34133-58-9 ]
[ 134165-33-6 ]

Reference： [1]Journal of Chemical Research, Miniprint,1991,p. 738 - 762

16
[ 151-50-8 ]
[ 619-72-7 ]
[ 34133-58-9 ]

Reference： [1]Journal of Chemical Research, Miniprint,1991,p. 738 - 762

17
[ 151-50-8 ]
[ 619-72-7 ]
[ 34133-58-9 ]
[ 19619-22-8 ]

Reference： [1]Journal of Chemical Research, Miniprint,1991,p. 738 - 762
[2]Journal of Chemical Research, Miniprint,1991,p. 738 - 762

18
[ 615-58-7 ]
[ 34133-58-9 ]

Reference： [1]Helvetica Chimica Acta,1984,vol. 67,p. 1580 - 1587

19
[ 36914-79-1 ]
[ 34133-58-9 ]

Reference： [1]Helvetica Chimica Acta,1984,vol. 67,p. 1580 - 1587

20
[ 52054-41-8 ]
[ 34133-58-9 ]

Reference： [1]Journal of Chemical Research, Miniprint,1992,p. 1831 - 1851

21
[ 34133-58-9 ]
4-(2-bromoethoxy)isophthalonitrile [ No CAS ]
[ 37142-39-5 ]

Yield	Reaction Conditions	Operation in experiment
64%		(i) 4-(2-Bromoethoxy)isophthalonitrile The sub-title compound was prepared in 64% yield according to the procedure described in Preparation K(i) above, using <strong>[34133-58-9]4-hydroxy-isophthalonitrile</strong> in place of 4-cyanophenol.
64%		(i) 4-(2-Bromoethoxy)isophthalonitrile The sub-title compound was prepared in 64% yield according to the procedure described in Preparation D(i) above, using <strong>[34133-58-9]4-hydroxy-isophthalonitrile</strong> in place of 4-cyanophenol.

Reference： [1]Patent: US2002/137766,2002,A1
[2]Patent: US6559143,2003,B1

22
[ 619-72-7 ]
[ 34133-58-9 ]
[ 636-46-4 ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide;	a. p-Nitrobenzonitrile (14.8g.) was heated at 100C. in dimethylsulphoxide (70 ml.) with dry powdered potassium cyanide (20g.) for 2 hours. The mixture was poured into water and an insoluble precipitate removed. Acidification of the filtrate and extraction with ether gave 2,4-dicyanophenol (did not melt but changed form at 240C.); on hydrolysis with concentrated hydrochloric acid this compound gave 4-hydroxyisophthalic acid, m.p. 310C.

Reference： [1]Patent: US3933807,1976,A

23
[ 34133-58-9 ]
[ 109-64-8 ]
[ 917226-68-7 ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 15h;	(iv) 4-(3-Bromopropoxy)isophthalonitrile4-Hydroxyisophthalonitrile (4.4 g, 0.03 mol; see step (iii) above) was dissolved in dry DMF (100 mL). 1,3-Dibromoprorhoane (36 g, 0.12 mol) and K2CO3 (8.2 g, 0.06 mol) were added. Then the reaction mixture was then stirred at 60C for 15 h before being cooled to RT and filtered through a Celite bed. The filtrate was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography EPO <DP n="64"/>over silica gel, using 2% ethyl acetate in petroleum ether as eluent, to yield the title compound (5.1 g, 63%) as pale yellow solid.

Reference： [1]Patent: WO2006/135316,2006,A1 .Location in patent: Page/Page column 62-63

24
[ 22433-92-7 ]
[ 34133-58-9 ]

Yield	Reaction Conditions	Operation in experiment
		(iii) 4-Hydroxyisophthalonitrile 4-Methoxyisophthalonitrile (2 g, 0.12 mol; see step (ii) above) was dissolved in quinoline (20 mL) and TMSI (2.7 mL, 0.018 mol) was added. The reaction mixture was stirred at 12O0C for 14 h, before being cooled to RT, acidified with cone. HCl and extracted with ethyl acetate. The organic layer was washed with 10% aqueous NaOH and the aqueous layer was acidified with 1 N HCl. The product was extracted with ethyl acetate, washed with water and brine and dried over Na2SO4. Solvent evaporation under reduced pressure afforded the sub-title compound (1.1 g, 61%) as pale brown solid. This was employed directly in the next step without further purification.

Reference： [1]Patent: WO2006/135316,2006,A1 .Location in patent: Page/Page column 62

25
[ 67-56-1 ]
[ 34133-58-9 ]
C₉H₈N₂O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 184 - 187

26
[ 34133-58-9 ]
[ 105-36-2 ]
[ 51282-86-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 2516 - 2519

27
potassium cyanide [ No CAS ]
[ 619-72-7 ]
[ 34133-58-9 ]

Yield	Reaction Conditions	Operation in experiment
		[0321] To a mixture of about 5 g (33.8 mmol) of 4-nitrobenzonitrile in 15 mL of DMSO was added 6.6 g (101.4 mmol) of KCN (ground). More DMSO (5 mL) was added, the mixture was stirred at 100 C for 2 h. The mixture was poured into H20, and the mixture was filtered through a Buchner funnel with H20. Concentrated HC1 was added to pH = 1-2, and EtOAc was added. The layers were separated, and the aqueous layer was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2S04, filtered, and concentrated. The dinitrile was used in the next reaction without further purification.

Reference： [1]Patent: WO2011/130383,2011,A1 .Location in patent: Page/Page column 95

28
[ 34133-58-9 ]
[ 54176-51-1 ]

Reference： [1]Patent: WO2011/130383,2011,A1

29
[ 34133-58-9 ]
[ 1342299-81-3 ]

Reference： [1]Patent: WO2011/130383,2011,A1

30
[ 34133-58-9 ]
[ 95088-64-5 ]

Reference： [1]Patent: WO2011/130383,2011,A1

31
[ 34133-58-9 ]
[ 1342299-76-6 ]

Reference： [1]Patent: WO2011/130383,2011,A1

32
[ 34133-58-9 ]
[ 1342299-77-7 ]

Reference： [1]Patent: WO2011/130383,2011,A1

33
[ 34133-58-9 ]
[ 1342299-78-8 ]

Reference： [1]Patent: WO2011/130383,2011,A1

34
[ 34133-58-9 ]
[ 1342299-79-9 ]

Reference： [1]Patent: WO2011/130383,2011,A1

35
[ 34133-58-9 ]
[ 1342299-80-2 ]

Reference： [1]Patent: WO2011/130383,2011,A1

36
[ 34133-58-9 ]
[ 1342299-85-7 ]

Reference： [1]Patent: WO2011/130383,2011,A1

37
[ 34133-58-9 ]
[ 1342299-86-8 ]

Reference： [1]Patent: WO2011/130383,2011,A1

38
[ 34133-58-9 ]
[ 5383-97-1 ]

Reference： [1]Patent: WO2011/130383,2011,A1

39
[ 34133-58-9 ]
[ 13253-23-1 ]

Reference： [1]Patent: WO2011/130383,2011,A1

40
[ 34133-58-9 ]
[ 1342299-87-9 ]

Reference： [1]Patent: WO2011/130383,2011,A1

41
[ 34133-58-9 ]
[ 1342299-88-0 ]

Reference： [1]Patent: WO2011/130383,2011,A1

42
[ 67-56-1 ]
[ 34133-58-9 ]
[ 5985-24-0 ]

Yield	Reaction Conditions	Operation in experiment
30%		[0322] A solution of dinitrile in 38 mL of H2S04 and 22 mL of H20 was stirred at 135 °C for 13 h. The temperature was decreased to 95 °C and 75 mL of MeOH was added. After 1.5 h the solution was poured into another flask and cooled to 0 °C to -5 °C. A NaOH solution (29.0 g (725mmol) of NaOH in 75 mL of water) was added dropwise with stirring to pH=l. Solid NaHC03 and H20 were added to pH = 5-7. The aqueous layer (mixture) was extracted with EtOAc and layers were separated. The mixture was roughly filtered through a cotton plug, EtOAc was added to the aqueous layer, and the layers were separated. The combined extracts were dried over Na2S04, filtered, and concentrated. Some of the crude product was loaded onto a loading cartridge, and the rest of the mixture was filtered through Celite with CH2C12, concentrated, and loaded onto a loading cartridge. Purification by flash silica gel chromatography (CombiFlash) (20percent EtOAc/hexanes) provided 2.15 g of the dimethyl 4- hydroxyisophathalate as a pale yellow solid in about 30percent yield.

Reference： [1]Patent: WO2011/130383,2011,A1 .Location in patent: Page/Page column 95-96

43
[ 78-77-3 ]
[ 34133-58-9 ]
[ 161718-81-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; potassium iodide; In dimethyl sulfoxide; at 70 - 75℃; for 16h;Product distribution / selectivity;	A mixture of 2,4-dibromo phenol (25 g), dimethylsulfoxide (125 ml), cuprous cyanide (26.6 g) and palladium acetate (1.25 g) was heated to 40-45C and then stirred for 4 hours. After completion of the reaction, potassium carbonate (30.11 g) followed by potassium iodide (6.58 g) were added to the reaction mixture and then heated to 70-75C. A solution of 1 -bromo-2-methylpropane (29.9 g) in dimethylsulfoxide (25 ml) was added to the reaction mixture and then stirred for 16 hours at 70-75C. After completion of the reaction, the reaction mixture was cooled to 25-30C and quenched it with water. The reaction mixture was extracted with ethylacetate, washed with water and distilled off the solvent completely under reduced pressure. Isopropyl alcohol was added to the obtained residue and distilled off the solvent at a temperature of below 60C. Isopropyl alcohol (50 ml) was added to the obtained residue and stirred for 30 minutes at 50-55C. Cooled the reaction mixture to 0-5C and stirred for 60 minutes at 0-5C. Filtered the solid, washed with isopropyl alcohol and then dried to get the title compound. Yield: 20 grams.

Reference： [1]Patent: WO2011/141933,2011,A2 .Location in patent: Page/Page column 43

44
[ 615-58-7 ]
copper(l) cyanide [ No CAS ]
[ 34133-58-9 ]

Yield	Reaction Conditions	Operation in experiment
	palladium diacetate; In dimethyl sulfoxide; at 40 - 45℃; for 4h;	A mixture of 2,4-dibromo phenol (25 g), dimethylsulfoxide (125 ml), cuprous cyanide (26.6 g) and palladium acetate (1.25 g) was heated to 40-45C and then stirred for 4 hours. After completion of the reaction, potassium carbonate (30.11 g) followed by potassium iodide (6.58 g) were added to the reaction mixture and then heated to 70-75C. A solution of 1 -bromo-2-methylpropane (29.9 g) in dimethylsulfoxide (25 ml) was added to the reaction mixture and then stirred for 16 hours at 70-75C. After completion of the reaction, the reaction mixture was cooled to 25-30C and quenched it with water. The reaction mixture was extracted with ethylacetate, washed with water and distilled off the solvent completely under reduced pressure. Isopropyl alcohol was added to the obtained residue and distilled off the solvent at a temperature of below 60C. Isopropyl alcohol (50 ml) was added to the obtained residue and stirred for 30 minutes at 50-55C. Cooled the reaction mixture to 0-5C and stirred for 60 minutes at 0-5C. Filtered the solid, washed with isopropyl alcohol and then dried to get the title compound. Yield: 20 grams.

Reference： [1]Patent: WO2011/141933,2011,A2 .Location in patent: Page/Page column 43

45
[ 615-58-7 ]
potassium ferrocyanide [ No CAS ]
[ 34133-58-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;palladium diacetate; In N,N-dimethyl-formamide; at 140 - 145℃; for 18h;	A mixture of 2,4-dibromophenol (25 g), potassium ferrocyanide (8.3 g), sodium carbonate (10.5 g), palladium acetate (0.2 g) in dimethyl formamide (125 ml) was heated to 140-145C and then stirred for 18 hours. After completion of the reaction, potassium carbonate (30.11 g) followed by potassium iodide (6.58 g) were added to the reaction mixture and then heated to 70-75C. A solution of l-bromo-2-methylpropane (29.9 g) in dimethyl formamide (25 ml) was added to the reaction mixture and then stirred for 16 hours at 70-75C. After completion of the reaction, the reaction mixture was cooled to 25-30C and quenched it with water. The reaction mixture was extracted with ethylacetate, washed with water and distilled off the solvent completely under reduced pressure. Isopropyl alcohol was added to the obtained residue and distilled off the solvent at a temperature of below 60C. Isopropyl alcohol (50 ml) was added to the obtained residue and stirred for 30 minutes at 50-55C. Cooled the reaction mixture to 0-5C and stirred for 60 minutes at 0-5 C. Filtered the solid, washed with isopropyl alcohol and then dried to get the title compound. Yield: 21 grams

Reference： [1]Patent: WO2011/141933,2011,A2 .Location in patent: Page/Page column 43-44

46
[ 34133-58-9 ]
febuxostat [ No CAS ]

Reference： [1]Patent: WO2011/141933,2011,A2
[2]Patent: WO2011/141933,2011,A2

47
[ 34133-58-9 ]
[ 163597-57-7 ]

Reference： [1]Patent: WO2011/141933,2011,A2

48
[ 34133-58-9 ]
[ 1350352-71-4 ]

Reference： [1]Patent: WO2011/141933,2011,A2
[2]Patent: WO2011/141933,2011,A2

49
[ 34133-58-9 ]
[ 1350352-72-5 ]

Reference： [1]Patent: WO2011/141933,2011,A2
[2]Patent: WO2011/141933,2011,A2

50
[ 683-57-8 ]
[ 34133-58-9 ]
[ 1380495-87-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 3732 - 3738

51
[ 34133-58-9 ]
[ 1380495-97-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 3732 - 3738

52
[ 34133-58-9 ]
[ 1169549-97-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 3732 - 3738

53
[ 90-02-8 ]
[ 34133-58-9 ]

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 181
[2]Patent: CN110156698,2019,A

54
[ 3328-70-9 ]
[ 34133-58-9 ]

Yield	Reaction Conditions	Operation in experiment
54.5%	With formic acid; hydroxylamine hydrochloride; sodium formate; In 1-methyl-pyrrolidin-2-one; for 6h;Reflux;	A solution of 11 (66g,0.44mol), hydroxylamine hydrochloride (91.7g, 1.32mol), HCOONa (110.7g, 1.63mol), NMP (30ml) in HCOOH (400ml) was refluxed for 6h. The reaction mixture was cooled at room temperature and stirred at 10C for 30min. Then the precipitate was filtered and recrystallized from 50% ethanol to give 12 (34.5g, 54.5%) as a gray white solid. mp: degraded at 190C. 1H NMR (600MHz, DMSO-d6) delta 12.42 (s, 1H), 8.27 (s, 1H), 7.93 (d, J=8.8Hz, 1H), 7.15 (d, J=8.8Hz, 1H). ESI-MS: m/z 142.8 [M-H] -.
3.4 g	With hydroxylamine hydrochloride; sodium formate; In 1-methyl-pyrrolidin-2-one; formic acid; for 6h;Reflux;	M-2 (66 g, 0.44 mol), hydroxylamine hydrochloride (91.7 g, 1.32 mol), sodium formate (110.7 g, 1.63 mol), NMP (30 ml) were placed in a reaction flask.Anhydrous formic acid (400 ml), refluxing for 6 h, a large amount of solid precipitated during the reaction.The reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature, stirred at 10 C for 30 min, suction filtered, and the filter cake was washed with water and dried. The obtained crude product was recrystallized from 50% ethanol to give 3.4 g of white solid, yield: 54.5 %

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 181
[2]Patent: CN110156698,2019,A .Location in patent: Paragraph 0059; 0074-0075

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[ 34133-58-9 ]
3-cyano-4-isopropoxybenzimidamide hydrochloride [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 181
[2]Patent: CN110156698,2019,A

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[ 34133-58-9 ]
3-cyano-4-isobutoxybenzimidamide hydrochloride [ No CAS ]