[ CAS No. 4394-00-7 ]

Name: 4394-00-7|2-((3-(Trifluoromethyl)phenyl)amino)nicotinic acid|98%
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{[proInfo.proName]} (Synonyms:Niflumic acid) ,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

Structure of 4394-00-7 * Storage: {[proInfo.prStorage]}

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Quality Control of [ 4394-00-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 4394-00-7 ]

SDS Specification

Alternatived Products of [ 4394-00-7 ]

Product Details of [ 4394-00-7 ]

CAS No. :	4394-00-7	MDL No. :
Formula :	-	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JZFPYUNJRRFVQU-UHFFFAOYSA-N
M.W :	-	Pubchem ID :	4488
Synonyms :	Niflumic acid

Calculated chemistry of [ 4394-00-7 ]

Physicochemical Properties

Num. heavy atoms :	20
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.08
Num. rotatable bonds :	4
Num. H-bond acceptors :	6.0
Num. H-bond donors :	2.0
Molar Refractivity :	65.74
TPSA :	62.22 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) :	-4.88 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.66
Log Po/w (XLOGP3) :	4.43
Log Po/w (WLOGP) :	4.69
Log Po/w (MLOGP) :	1.52
Log Po/w (SILICOS-IT) :	2.6
Consensus Log Po/w :	2.98

Druglikeness

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

Water Solubility

Log S (ESOL) :	-4.56
Solubility :	0.00776 mg/ml ; 0.0000275 mol/l
Class :	Moderately soluble
Log S (Ali) :	-5.45
Solubility :	0.00099 mg/ml ; 0.00000351 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-4.85
Solubility :	0.00399 mg/ml ; 0.0000141 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.2

Safety of [ 4394-00-7 ]

Signal Word:		Class:
Precautionary Statements:		UN#:
Hazard Statements:		Packing Group:

Application In Synthesis of [ 4394-00-7 ]

* 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 [ 4394-00-7 ]
Downstream synthetic route of [ 4394-00-7 ]

[ 4394-00-7 ] Synthesis Path-Upstream 1~14

1
[ 929257-58-9 ]
[ 5835-79-0 ]
[ 4394-00-7 ]

Reference： [1] Arzneimittel-Forschung/Drug Research, 2006, vol. 56, # 11, p. 744 - 752

2
[ 2942-59-8 ]
[ 98-16-8 ]
[ 4394-00-7 ]

Reference： [1] Journal of Medicinal Chemistry, 1990, vol. 33, # 10, p. 2697 - 2706
[2] Medicinal Chemistry Research, 2013, vol. 22, # 5, p. 2411 - 2420

3
[ 137488-50-7 ]
[ 4394-00-7 ]

Reference： [1] Archiv der Pharmazie, 1991, vol. 324, # 11, p. 887 - 890

4
[ 137488-34-7 ]
[ 4394-00-7 ]

Reference： [1] Archiv der Pharmazie, 1991, vol. 324, # 11, p. 887 - 890

5
[ 137488-47-2 ]
[ 4394-00-7 ]

Reference： [1] Archiv der Pharmazie, 1991, vol. 324, # 11, p. 887 - 890

6
[ 137488-49-4 ]
[ 4394-00-7 ]

Reference： [1] Archiv der Pharmazie, 1991, vol. 324, # 11, p. 887 - 890

7
[ 137488-48-3 ]
[ 4394-00-7 ]

Reference： [1] Archiv der Pharmazie, 1991, vol. 324, # 11, p. 887 - 890

8
[ 137138-26-2 ]
[ 4394-00-7 ]

Reference： [1] Archiv der Pharmazie, 1991, vol. 324, # 9, p. 547 - 550

9
[ 735318-84-0 ]
[ 107-10-8 ]
[ 4394-00-7 ]
[ 104749-83-9 ]

Reference： [1] Arzneimittel-Forschung/Drug Research, 2006, vol. 56, # 9, p. 631 - 639

10
[ 533925-39-2 ]
[ 39096-01-0 ]
[ 4394-00-7 ]
[ 109-89-7 ]

Reference： [1] Arzneimittel-Forschung/Drug Research, 2006, vol. 56, # 9, p. 631 - 639

11
[ 533925-45-0 ]
[ 110-91-8 ]
[ 51068-78-1 ]
[ 4394-00-7 ]

Reference： [1] Arzneimittel-Forschung/Drug Research, 2006, vol. 56, # 9, p. 631 - 639

12
[ 929257-58-9 ]
[ 5835-79-0 ]
[ 4394-00-7 ]

Reference： [1] Arzneimittel-Forschung/Drug Research, 2006, vol. 56, # 11, p. 744 - 752

13
[ 929257-57-8 ]
[ 4344-62-1 ]
[ 4394-00-7 ]

Reference： [1] Arzneimittel-Forschung/Drug Research, 2006, vol. 56, # 11, p. 744 - 752

14
[ 533925-45-0 ]
[ 110-91-8 ]
[ 51068-78-1 ]
[ 4394-00-7 ]

Reference： [1] Arzneimittel-Forschung/Drug Research, 2006, vol. 56, # 9, p. 631 - 639

[ 4394-00-7 ] Synthesis Path-Downstream 1~69

1
[ 2942-59-8 ]
[ 98-16-8 ]
[ 4394-00-7 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2697 - 2706
[2]Medicinal Chemistry Research,2013,vol. 22,p. 2411 - 2420

2
[ 6940-49-4 ]
[ 4394-00-7 ]
[ 66898-62-2 ]

Yield	Reaction Conditions	Operation in experiment
52% (20.5 g)	With triethylamine; In water; acetone;	EXAMPLE II Triethylamine (20 ml) and 3-bromophthalide (21.3 g) were added to a suspension of 2(3'-trifluormethylanilino)-nicotinic acid (28,2 g in 500 ml of acetone). The mixture was refluxed during 4 hours. The obtained greenish yellow suspension was poured into 6000 ml of water, which was previously heated at 50 C. The stirred reaction mixture was cooled to 5 C., and the formed precipitate was filtered and washed with cool water. Yield: 52% (20.5 g) of phthalidyl 2-(3'-trifluormethylanilino)-pyridin-3-carboxylate, m.p: 162-164 C. Applying thin layer chromatography, only one spot appeared in the chromatogram (silicagel; benzene-ethanol/100:2/). IR spectrum was equivalent to IR spectrum of the compound obtained following the example I.

Reference： [1]Farmaco, Edizione Pratica,1981,vol. 36,p. 372 - 385
[2]Patent: US4168313,1979,A

3
[ 50-00-0 ]
[ 4394-00-7 ]
[ 137488-34-7 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 821 - 825

4
[ 18997-19-8 ]
[ 4394-00-7 ]
[ 66898-68-8 ]

Reference： [1]Farmaco, Edizione Pratica,1981,vol. 36,p. 372 - 385

5
[ 534-15-6 ]
[ 4394-00-7 ]
[ 137488-50-7 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 821 - 825

6
[ 97-97-2 ]
[ 4394-00-7 ]
[ 137488-49-4 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 821 - 825

7
[ 134674-20-7 ]
[ 4394-00-7 ]
[ 134674-32-1 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 307 - 311

8
[ 134674-19-4 ]
[ 4394-00-7 ]
[ 134674-25-2 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 307 - 311

9
[ 132063-56-0 ]
[ 4394-00-7 ]
[ 134674-39-8 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 307 - 311

10
[ 4394-00-7 ]
[ 78-95-5 ]
[ 137138-26-2 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 547 - 550

11
[ 4394-00-7 ]
[ 122-51-0 ]
[ 137488-48-3 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 821 - 825

12
[ 4394-00-7 ]
[ 62-53-3 ]
[ 31991-16-9 ]

Reference： [1]Synthesis,1980,p. 547 - 551

13
[ 4394-00-7 ]
[ 95-53-4 ]
[ 31991-24-9 ]

Reference： [1]Synthesis,1980,p. 547 - 551

14
[ 4394-00-7 ]
[ 149-73-5 ]
[ 137488-47-2 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 821 - 825

15
[ 4394-00-7 ]
[ 59272-27-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium sulfate; In tetrahydrofuran; diethyl ether; ethyl acetate;	EXAMPLE 1 2-(3-Trifluoromethylphenyl)amino-3-hydroxymethylpyridine Formula (V): X=Z2 =H, Z1 =3--CF3 A solution of 200 g of 2-(3-trifluoromethylphenyl)aminonicotinic acid in 500 ml of anhydrous tetrahydrofuran is added dropwise to a suspension of 52 g of lithium aluminum hydride in 1000 ml of anhydrous ethyl ether. When the addition is complete, the reaction mixture is refluxed for 3 h. After cooling, the excess hydride is destroyed by the addition of ethyl acetate followed by a saturated aqueous solution of sodium sulfate. The precipitate formed is filtered off and washed with ether. The combined filtrates are evaporated under vacuum and 185.2 g of 2-(3-trifluoromethylphenyl)amino-3-hydroxymethylpyridine are recovered in the form of crystals melting at 103-105 C.
	With sodium sulfate; In tetrahydrofuran; diethyl ether; ethyl acetate;	EXAMPLE 1 2-(3-Trifluoromethylphenyl)amino-3-hydroxy-methylpyridine Formula (V): X=H; R2 =3--CF3 -phenyl A solution of 200 g of 2-(3-trifluoromethyl-phenyl)aminonicotinic acid in 500 ml of anhydrous tetrahydrofuran is added dropwise to a suspension of 52 g of lithium aluminum hydride in 1000 ml of anhydrous ethyl ether. When the addition is complete, the reaction mixture is refluxed for 3 h. After cooling, the excess hydride is destroyed by the addition of ethyl acetate followed by a saturated aqueous solution of sodium sulfate. The precipitate formed is filtered off and washed with ether. The combined filtrates are evaporated under vacuum and 185.2 g of 2-(3-trifluoromethylphenyl)amino-3-hydroxymethylpyridine are recovered in the form of crystals melting at 103-105 C. The following derivatives of formula (V) are prepared by this method:

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2697 - 2706
[2]Molecular Pharmacology,2006,vol. 69,p. 165 - 173
[3]Patent: US5364860,1994,A
[4]Patent: US5663181,1997,A

16
[ 137488-50-7 ]
[ 4394-00-7 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 887 - 890

17
[ 137488-34-7 ]
[ 4394-00-7 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 887 - 890

18
[ 137488-47-2 ]
[ 4394-00-7 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 887 - 890

19
[ 137488-49-4 ]
[ 4394-00-7 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 887 - 890

20
[ 137488-48-3 ]
[ 4394-00-7 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 887 - 890

21
[ 137138-26-2 ]
[ 4394-00-7 ]

Reference： [1]Archiv der Pharmazie,1991,vol. 324,p. 547 - 550

22
[ 4344-62-1 ]
[ 4394-00-7 ]
[ 929257-57-8 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 744 - 752

23
[ 929257-57-8 ]
[ 4344-62-1 ]
[ 4394-00-7 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 744 - 752

24
[ 4394-00-7 ]
[ 64-19-7 ]
2-diethylaminoethyl 2-[[3-(trifluoromethyl)phenyl]amino]-3-pyridinecarboxylate acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86.1%		Preparation of diethylaminoethyl 2-[[3-(trifluoromethyl)phenyl]amino] -3-pyridinecarboxylate.AcOH; [36] 28.2 g (0.1 mol) of 2-[[3-(trifluoromethyl)phenyl]amino]-3-pyridinecarboxylic acid was dissolved in 200 ml of 10% NaHCO . 100 ml of acetone and 43 g (0.15mol) of diethylaminoethyl bromide.HBr was added into the mixture and the mixture was stirred for 5 hours at RT. The mixture is extracted with ethyl acetate (2 x 300 ml). The ethyl acetate solution is dried over anhydrous sodium sulfate. 6 g of acetic acid is added into the solution. The solution was concentrated in vacuo to 100 ml. Then 300 ml of hexane was added into the solution. The solid product was collected by filtration and washed with hexane (3 x 100 ml). After drying, it yielded 38 g of the desired product (86.1%). Hygroscopic product; Solubility in water: 400 mg/ml; Elementary analysis: C H F N21 26 3 3O4; MW: 441.44. Calculated % C: 57.14; H: 5.94; F: 12.91, N: 9.52; O: 14.50; Found % C: 57.11; H: 5.97; F: 12.92; N: 9.50; O: 14.50. 1H-NMR (400 MHz, D O): delta: 1.44 (t, 6H), 2.11 (s, 3H), 3.23 (m, 4H), 3.70 (m, 2H), 4.60 (m, 2H), 6.46 (m, IH), 6.65 (s, IH), 6.77 (m, IH), 6.83 (m, IH), 6.90 (m, IH), 8.00 (m, IH), 8.38 (m, 1 H)

Reference： [1]Patent: WO2008/29199,2008,A1 .Location in patent: Page/Page column 15

26
[ 735318-84-0 ]
[ 107-10-8 ]
[ 4394-00-7 ]
[ 104749-83-9 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 631 - 639

27
[ 13916-39-7 ]
[ 4394-00-7 ]
[ 735318-84-0 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 631 - 639

28
[ 533925-39-2 ]
[ 39096-01-0 ]
[ 4394-00-7 ]
[ 109-89-7 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 631 - 639

29
[ 1709-06-4 ]
[ 4394-00-7 ]
2-(3-trifluoromethyl-phenylamino)nicotinic acid [bis(2-hydroxyethyl)carbamoyl]-methyl ester [ No CAS ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 631 - 639

30
[ 533925-45-0 ]
[ 110-91-8 ]
[ 51068-78-1 ]
[ 4394-00-7 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 631 - 639

31
[ 4593-18-4 ]
[ 4394-00-7 ]
2-(3-trifluoromethyl-phenylamino)nicotinic acid 2-(2-methyl-piperidin-1-yl)-2-oxo-ethyl ester [ No CAS ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 631 - 639

32
[ 4593-19-5 ]
[ 4394-00-7 ]
2-(3-trifluoromethyl-phenylamino)nicotinic acid 2-(3-methyl-piperidin-1-yl)-2-oxo-ethyl ester [ No CAS ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 631 - 639

33
[ 4593-20-8 ]
[ 4394-00-7 ]
2-(3-trifluoromethyl-phenylamino)nicotinic acid 2-(4-methyl-piperidin-1-yl)-2-oxo-ethyl ester [ No CAS ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 631 - 639

34
[ 137860-92-5 ]
[ 4394-00-7 ]
2-(3-trifluoromethyl-phenylamino)nicotinic acid 2-oxo-2-thiomorpholin-4-yl-ethyl ester [ No CAS ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 631 - 639

35
[ 4394-00-7 ]
[ 77580-36-0 ]
2-(3-trifluoromethyl-phenylamino)-nicotinic acid 2-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-2-oxo-ethyl ester [ No CAS ]

Reference： [1]Arzneimittel-Forschung/Drug Research,2006,vol. 56,p. 631 - 639

36
[ 4394-00-7 ]
[ 37102-09-3 ]

Reference： [1]Journal of Pharmacy and Pharmacology,2002,vol. 54,p. 283 - 288

37
[ 4394-00-7 ]
3-Methyl-1-(3-trifluoromethyl-phenyl)-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2697 - 2706

38
[ 4394-00-7 ]
[ 127555-31-1 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2697 - 2706

39
[ 4394-00-7 ]
[ 128271-40-9 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2697 - 2706

40
[ 4394-00-7 ]
[ 127555-40-2 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2697 - 2706

41
[ 4394-00-7 ]
3-Methyl-3-phenylsulfanyl-1-(3-trifluoromethyl-phenyl)-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2697 - 2706

42
[ 4394-00-7 ]
(3-Chloromethyl-pyridin-2-yl)-(3-trifluoromethyl-phenyl)-amine; hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2697 - 2706

43
[ 32315-10-9 ]
[ 4394-00-7 ]
C₁₄H₇F₃N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine;	The preparation of this class of mucin synthesis inhibitors was accomplished by the following scheme: e 0 TphosHem. dclryde x o RI R O p 0 Fomacncid % I XR,"'"""" X h x x w x'ai X-CorN Z-NH The preparation of this class of mucin synthesis inhibitors was accomplished by the following general scheme. Differing primarily in the preparation of the P-KETO phosphonate. For the analogues containing diaryl amine, the cyclic anhydride was prepared. Attempts to prepare the phosphonate directly from the methyl ester gave relatively poor results. The yields were variable and poor. The preparation of the phosphonate from the isatoic anhydride gave improved results. For other diarylether and thioether analogues the methyl ester yielded satisfactory results.

Reference： [1]Patent: WO2004/113286,2004,A2 .Location in patent: Page 26-27

44
[ 100-02-7 ]
[ 4394-00-7 ]
[ 503437-41-0 ]

Yield	Reaction Conditions	Operation in experiment
31%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 40℃; for 16h;	4-Nitrophenyl 2-[3-(trifluoromethyl)phenyl]amino}nicotinate To a warmed (40 C.) suspension of niflumic acid (10.0 g, 35.4 mmol) and 4-nitrophenol (4.9 g, 35.4 mmol) in CH2Cl2 (80 mL) was added a suspension of EDCI (6.8 g, 35.4 mmol) in CH2Cl2 (20 mL). The reaction was stirred for 16 h, and then cooled to room temperature. The solution was quenched with water (50 mL), and the aqueous layer was extracted with CH2Cl2. The combined organic extracts were washed with water and dried over Na2SO4. The solvent was removed in vacuo, and the residue was purified by trituration with Hex:CH2Cl2 to afford 4-Nitrophenyl 2-[3-(trifluoromethyl)phenyl]amino}nicotinate (4.5 g, 31%): LCMS RT: 4.03 min, MH+: 404.1.

Reference： [1]Patent: US6677352,2004,B1 .Location in patent: Page/Page column 62

45
hydride of aluminium [ No CAS ]
[ 4394-00-7 ]
[3-(trifluoromethyl)phenyl]2-amino hydroxy 3-methyl pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With lithium; sodium sulfate; In tetrahydrofuran; diethyl ether; ethyl acetate;	EXAMPLE 1 [3-(trifluoromethyl)phenyl]2-amino hydroxy 3-methyl pyridine Formula III: R1 =Y=H; X=m-CF3 To a suspension of 52 g of double hydride of aluminium and lithium in 1000 ml of anhydrous ethyl ether, there is added drop by drop a solution of 200 g of 2-(3-trifluoromethyl phenyl amino)nicotinic acid in 500 ml of anhydrous tetrahydrofuran. At the end of the addition, the reaction mixture is heated under reflux for 3 hours. After cooling, the excess double hydride is destroyed by addition of ethyl acetate, then of a saturated aqueous solution of sodium sulfate. The precipitate formed is drained and washed with ether. The collected filtrates are evaporated in vacuo and 185.2 g of [3-(trifluoromethyl)phenyl]2-amino hydroxy 3-methyl pyridine are recovered, in the form of crystals, melting point: 103-105 C.

Reference： [1]Patent: US4622328,1986,A

46
[ 103-90-2 ]
[ 4394-00-7 ]
[ 1210908-43-2 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 2286 - 2298

47
[ 1334486-39-3 ]
[ 4394-00-7 ]
[ 1334486-56-4 ]

Yield	Reaction Conditions	Operation in experiment
37.8%		Niflumic acid (3.346g, 1 1.8 mmol) was dissolved in DMSO (30 mL). Triethylamine (1.66 mL, 1 1.8 mmol) was then added and the reaction mixture was stirred for 50 min at room temperature. A solution of O -(chloromethyl)-l -(N- isopropylamino)diazen-l -ium-l ,2-diolate in DMSO (25 mL) was added drop wise to the reaction mixture. The reaction mixture was stirred for 15 h and after completion of the reaction; the mixture was quenched with ethyl acetate (80mL). The organic layer was washed with dil. HC1 (5 x 60 mL), dried over sodium sulfate and evaporated to obtain the crude product. Purification was performed by column chromatography, first using 22% ethyl acetate: hexane and then 1 % ethyl acetate: dichloromethane to obtain IPA/NO-niflumic (1.10 g, 2.6 mmol, 37.8%) as a light yellow solid. NMR (CDC13): delta 1.168 [d, J=6.5 Hz, 6H, (CH3)2], 3.985 [s, J=6.5 Hz, IH, CH), 5.995 (s, 2H, OCH20), 6.785 [dd, Jl= 5Hz, J2=8Hz, IH arom] 7.287-7.444 [m, 2H arom], 7.81 [d, J=8Hz, IH arom], 8.048 [s, IH arom] 8.284- 8.304 [dd, Jl=2Hz, J2= 8Hz, IH, arom] 8.417-8.431 [dd, Jl=5Hz Hz, J2=2Hz, IH, arom], 10.173 [s, IotaEta, NuEta]. 13C NMR (CDC13): 5 20.37, 49.24, 87.56, 106.18, 1 14.1 1, 1 17.34, 1 19.33, 123.72, 129.20, 139.98, 140.61 , 153.91, 156.02, 165.98 Elemental analysis(C13H17N306): C=50.16; H-5.50; N=13.50 (theoretical), C=49.92; H=5.42; N=13.42 (experimental), MS (LCQ, ESI ionization method): 334.1 (MNa+ peak), UV: epsilon (lambda24omicronetaeta = 7.87mM~ 1

Reference： [1]Patent: WO2011/116336,2011,A1 .Location in patent: Page/Page column 53-54

48
[ 952492-09-0 ]
[ 4394-00-7 ]
[ 1334486-50-8 ]

Yield	Reaction Conditions	Operation in experiment
66.2%		Niflumic acid (6.2 l g, 22mmol) was dissolved in DMSO (150 mL). Triethylamine (3.07 mL, 22 mmol) was then added and the reaction mixture was stirred for 30 min at room temperature. A solution of ( 2-(Chloromethyl)-l -(N,7V- Diethylamino)diazen-l -ium-l ,2-diolate (4.0g, 22mmol) in DMSO (50 mL) was added drop wise to the reaction mixture. The reaction mixture was stirred for 24hr and after completion of the reaction; it was quenched with ethyl acetate (150mL). The organic layer was washed with saturated NaHC03 solution (5 x 100 mL), dried over sodium sulfate and then evaporated to obtain the crude product. Further purification was performed by gradient columnchromatography (30% ethyl acetate-hexane) to obtain 6.2g (66.2%) of pure product. NMR (CDCI3): delta 1.07 [t, J=3.5 Hz, 6H, (CH3)2], 3.18 [q, J=3.5 Hz, 4H, CH2), 6.04 (s, 2H, OCH20), 6.75 [dd, Jl= 5Hz, J2=8Hz, 1H arom] 7.25-7.41 [m, 2H arom], 7.80 [d, J=8Hz, 1H arom], 8.07 [s, 1H arom] 8.24-8.26[dd, Jl=2Hz, J2= 8Hz, 1H, arom] 8.39-8.40 [dd, Jl=4.5 Hz, J2=2Hz, 1H, arom], 10.16 [s, 1H, NH] .3C NMR (CDC13): delta 1 1.45, 47.98 87.73, 106.20, 1 14.07, 117.32, 1 19.28, 123.70, 129.160, 140.01, 140.47, 153.84, 156.01, 165.8 Elemental analysis (Ci3H17N306): C=50.59; H=4.72; N=16.39 (theoretical), C=50.82; H=4.55; N=16.16 (experimental), MS (LCQ, ESI): 450.1 (MNa+ peak).

Reference： [1]Patent: WO2011/116336,2011,A1 .Location in patent: Page/Page column 52-53

49
[ 98-92-0 ]
[ 4394-00-7 ]
[ 1313599-96-0 ]

Reference： [1]Crystal Growth and Design,2011,vol. 11,p. 3522 - 3528

50
[ 67-56-1 ]
manganese(II) chloride tetrahydrate [ No CAS ]
[ 4394-00-7 ]
[ 1428525-44-3 ]

Reference： [1]Polyhedron,2013,vol. 53,p. 215 - 222

51
[ 4394-00-7 ]
[ 204928-98-3 ]