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[ CAS No. 5538-51-2 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}

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

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Chemical Structure| 5538-51-2

Chemical Structure| 5538-51-2

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Quality Control of [ 5538-51-2 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 5538-51-2 ]

Product Details of [ 5538-51-2 ]

CAS No. :	5538-51-2	MDL No. :	MFCD00000663
Formula :	C₉H₇ClO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	DSGKWFGEUBCEIE-UHFFFAOYSA-N
M.W :	198.60	Pubchem ID :	79668
Synonyms :

Calculated chemistry of [ 5538-51-2 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.11
Num. rotatable bonds :	3
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	48.12
TPSA :	43.37 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.97 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.0
Log Po/w (XLOGP3) :	2.17
Log Po/w (WLOGP) :	1.99
Log Po/w (MLOGP) :	1.86
Log Po/w (SILICOS-IT) :	2.22
Consensus Log Po/w :	2.05

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.58
Solubility :	0.52 mg/ml ; 0.00262 mol/l
Class :	Soluble
Log S (Ali) :	-2.71
Solubility :	0.384 mg/ml ; 0.00193 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.04
Solubility :	0.18 mg/ml ; 0.000906 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.64

Safety of [ 5538-51-2 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P260-P280-P303+P361+P353-P304+P340+P310-P305+P351+P338	UN#:	3261
Hazard Statements:	H314	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 5538-51-2 ]

* 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 [ 5538-51-2 ]
Downstream synthetic route of [ 5538-51-2 ]

[ 5538-51-2 ] Synthesis Path-Upstream 1~6

1
[ 5538-51-2 ]
[ 1076-38-6 ]

Reference： [1] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1981, vol. 20, # 6, p. 511

2
[ 121-66-4 ]
[ 5538-51-2 ]
[ 55981-09-4 ]

Reference： [1] European Journal of Medicinal Chemistry, 1978, vol. 13, # 6, p. 539 - 543

3
[ 5538-51-2 ]
[ 1466-82-6 ]

Reference： [1] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 9, p. 933

4
[ 50-78-2 ]
[ 5538-51-2 ]
[ 1466-82-6 ]

Reference： [1] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 9, p. 933

5
[ 69-72-7 ]
[ 5538-51-2 ]
[ 530-75-6 ]

Reference： [1] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 10, p. 1115
[2] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 9, p. 928

6
[ 5538-51-2 ]
[ 19311-91-2 ]

Reference： [1] Annali di Chimica (Rome, Italy), 1955, vol. 45, p. 205,213

[ 5538-51-2 ] Synthesis Path-Downstream 1~88

1
[ 60-27-5 ]
[ 5538-51-2 ]
<i>N</i>-(1-methyl-4-oxo-4,5-dihydro-1<i>H</i>-imidazol-2-yl)-salicylamide [ No CAS ]

Reference： [1]Patent: US2401522,1943,

2
[ 519-37-9 ]
[ 5538-51-2 ]
2-acetoxy-benzoic acid-[2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-ethyl ester] [ No CAS ]

Reference： [1]Annali di Chimica,1956,vol. 46,p. 99,102,104
[2]Annali di Chimica,1956,vol. 46,p. 99,102,104

3
[ 66-76-2 ]
[ 5538-51-2 ]
bis-[4-(2-acetoxy-benzoyloxy)-2-oxo-2<i>H</i>-chromen-3-yl]-methane [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1944,vol. 66,p. 900

4
[ 124-02-7 ]
[ 5538-51-2 ]
[ 106950-71-4 ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine In dichloromethane at 0 - 20℃;	General procedure for the synthesis of acyl diallylamines (1aa-vv). General procedure: Triethylamine (126 mg, 1.25 mmol) was added dropwise to a stirred solution of diallylamine (107 mg, 1.10 mmol) in dry dichloromethane (3.0 mL) at 0 °C. Then, the formyl chloride (1.00 mmol) was slowly added to the mixture. The solution was allowed to warm to room temperature and stirred till the end of the reaction. The reaction mixture was poured into a seperatory funnel containing water (3.0 mL). The aqueous was removed and the organic phase was subsequently washed with 1 M HCl(3.0 mL), and brine (3.0 mL), dried over Na2SO4 and filtered. The volatiles were removed in vacuo and the residue was subjected to flash column chromatography to give the acyl diallylamines.
	With 4-methyl-morpholine

Reference： [1]Chen, Weiqiang; Li, Hui-Jing; Liu, Ying; Nan, Xiang; Wu, Yan-Chao; Zhang, Yin-Lin [Synthesis, 2019, vol. 51, # 19, p. 3651 - 3666]
[2]Yale [Journal of the American Chemical Society, 1957, vol. 79, p. 4762,4763]

5
[ 69-72-7 ]
[ 5538-51-2 ]
[ 530-75-6 ]

Reference： [1]Patent: DE236196,
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 10,p. 1115

6
[ 50-78-2 ]
[ 5538-51-2 ]
[ 1466-82-6 ]

Reference： [1]Patent: DE201325,
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 9,p. 933

7
[ 5538-51-2 ]
[ 1466-82-6 ]

Reference： [1]Patent: DE201325,
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 9,p. 933

8
[ 121-66-4 ]
[ 5538-51-2 ]
[ 55981-09-4 ]

Reference： [1]European Journal of Medicinal Chemistry,1978,vol. 13,p. 539 - 543

9
[ 826-85-7 ]
[ 5538-51-2 ]
[ 79442-87-8 ]

Reference： [1]Journal of Heterocyclic Chemistry,1981,vol. 18,p. 747 - 750

10
[ 6265-73-2 ]
[ 5538-51-2 ]
[ 88354-02-3 ]
[ 88353-97-3 ]

Reference： [1]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1983,vol. 37,p. 351 - 359

11
[ 150-76-5 ]
[ 5538-51-2 ]
[ 1200-06-2 ]
[ 10268-61-8 ]
[ 83570-56-3 ]

Reference： [1]Tetrahedron,1982,vol. 38,p. 1523 - 1526

12
[ 2450-71-7 ]
[ 5538-51-2 ]
[ 128064-20-0 ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine In dichloromethane at 20℃; for 24h;	2.1.2.1.4 Method D General procedure: 0.002 mol of propargylamine (128.1 µL) and 0.003 mol of triethylamine were dissolved in 10 mL of DCM. Appropriated acyl chloride (0.003 mol) was added slowly under vigorous stirring. The reaction mixture was stirred for 24 h at room temperature. The mixture was evaporated till dryness and suspended in ethyl acetate. The insoluble portion was filtered off. The filtrate was washed successively by hydrochloric acid (0.1 M), sodium bicarbonate solution (5%) and saturated brine. The organic phase was dried using sodium sulphate and evaporated till dryness to provide pure crystals. Alternatively, the filtrate was purified using column chromatography (silica gel 60, a mixture with a ratio of toluene to ethyl acetate of 4:1 (v/v) was the mobile phase). When purifying ester 2a, the mobile phase was supplemented by 209.0 µL (0.0015 mol) of triethylamine to preserve slightly basic conditions.
72%	In dichloromethane for 0.5h;

Reference： [1]Krátký, Martin; Vu, Quynh Anh; Štěpánková, Šárka; Maruca, Annalisa; Silva, Tiago Barros; Ambrož, Martin; Pflégr, Václav; Rocca, Roberta; Svrčková, Katarína; Alcaro, Stefano; Borges, Fernanda; Vinšová, Jarmila [Bioorganic Chemistry, 2021, vol. 116]
[2]Freedman, Jules; Huber, Edward W. [Journal of Heterocyclic Chemistry, 1990, vol. 27, # 4, p. 343 - 346]

13
[ 38160-63-3 ]
[ 5538-51-2 ]
2-(2-Acetoxy-benzoylamino)-4-hydroxy-benzoic acid [ No CAS ]

Reference： [1]Tetrahedron Letters,1990,vol. 31,p. 2647 - 2648

14
[ 38160-63-3 ]
[ 5538-51-2 ]
[ 117979-57-4 ]

Reference： [1]Journal of Heterocyclic Chemistry,1988,vol. 25,p. 715 - 718

15
[ 558-42-9 ]
[ 5538-51-2 ]
2-Acetoxy-benzoic acid 2-chloro-1,1-dimethyl-ethyl ester [ No CAS ]
[ 132305-33-0 ]

Reference： [1]Acta Chemica Scandinavica,1990,vol. 44,p. 952 - 956
[2]Acta Chemica Scandinavica,1990,vol. 44,p. 952 - 956

16
[ 1135-14-4 ]
[ 5538-51-2 ]
[ 77711-75-2 ]

Reference： [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 889 - 893

17
[ 702-98-7 ]
[ 5538-51-2 ]
[ 132362-30-2 ]
2-Acetoxy-benzoic acid 2-methyl-adamantan-2-yl ester [ No CAS ]

Reference： [1]Acta Chemica Scandinavica,1990,vol. 44,p. 952 - 956
[2]Acta Chemica Scandinavica,1990,vol. 44,p. 952 - 956

18
[ 1529-17-5 ]
[ 5538-51-2 ]
[ 52602-04-7 ]
[ 134-55-4 ]

Reference： [1]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1983,vol. 37,p. 351 - 359

19
[ 15258-73-8 ]
[ 5538-51-2 ]
2-(2,6-Dichloro-benzyloxy)-2-methyl-benzo[1,3]dioxin-4-one [ No CAS ]
2-Acetoxy-benzoic acid 2,6-dichloro-benzyl ester [ No CAS ]

Reference： [1]Acta Chemica Scandinavica,1989,vol. 43,p. 793 - 798
[2]Acta Chemica Scandinavica,1989,vol. 43,p. 793 - 798

20
[ 16700-55-3 ]
[ 5538-51-2 ]
[ 127042-09-5 ]
2-Acetoxy-benzoic acid 2,6-dimethoxy-benzyl ester [ No CAS ]

Reference： [1]Acta Chemica Scandinavica,1989,vol. 43,p. 793 - 798

21
[ 16700-55-3 ]
[ 5538-51-2 ]
2-Acetoxy-benzoic acid 2,6-dimethoxy-benzyl ester [ No CAS ]

Reference： [1]Acta Chemica Scandinavica,1989,vol. 43,p. 793 - 798

22
[ 1462-03-9 ]
[ 5538-51-2 ]
2-Acetoxy-benzoic acid 1-methyl-cyclopentyl ester [ No CAS ]
[ 132362-29-9 ]

Reference： [1]Acta Chemica Scandinavica,1990,vol. 44,p. 952 - 956
[2]Acta Chemica Scandinavica,1990,vol. 44,p. 952 - 956

23
[ 446-51-5 ]
[ 5538-51-2 ]
2-(2-Fluoro-benzyloxy)-2-methyl-benzo[1,3]dioxin-4-one [ No CAS ]
2-Acetoxy-benzoic acid 2-fluoro-benzyl ester [ No CAS ]

Reference： [1]Acta Chemica Scandinavica,1989,vol. 43,p. 793 - 798
[2]Acta Chemica Scandinavica,1989,vol. 43,p. 793 - 798

24
[ 346-06-5 ]
[ 5538-51-2 ]
2-Methyl-2-(2-trifluoromethyl-benzyloxy)-benzo[1,3]dioxin-4-one [ No CAS ]
2-Acetoxy-benzoic acid 2-trifluoromethyl-benzyl ester [ No CAS ]

Reference： [1]Acta Chemica Scandinavica,1989,vol. 43,p. 793 - 798
[2]Acta Chemica Scandinavica,1989,vol. 43,p. 793 - 798

25
[ 20059-73-8 ]
[ 5538-51-2 ]
Acetic acid 2-[4-(2-dimethylamino-ethoxy)-benzylcarbamoyl]-phenyl ester [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1992,vol. 40,p. 202 - 211

26
[ 32631-29-1 ]
[ 5538-51-2 ]
[ 77711-78-5 ]

Yield	Reaction Conditions	Operation in experiment
30%	With pyridine In diethyl ether for 2h;

Reference： [1]Marcincal-Lefebvre; Gesquiere; Lemer; Dupuis [Journal of Medicinal Chemistry, 1981, vol. 24, # 7, p. 889 - 893]

27
[ 19064-18-7 ]
[ 5538-51-2 ]
2-(2,6-Difluoro-benzyloxy)-2-methyl-benzo[1,3]dioxin-4-one [ No CAS ]
2-Acetoxy-benzoic acid 2,6-difluoro-benzyl ester [ No CAS ]

Reference： [1]Acta Chemica Scandinavica,1989,vol. 43,p. 793 - 798
[2]Acta Chemica Scandinavica,1989,vol. 43,p. 793 - 798

28
[ 32854-09-4 ]
[ 5538-51-2 ]
[ 157598-35-1 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 2889 - 2895

29
[ 1405-86-3 ]
[ 5538-51-2 ]
penta-O-acetylsalicyloylglycyrrhizic acid [ No CAS ]

Reference： [1]Russian Journal of General Chemistry,1994,vol. 64,p. 1809 - 1815
Zhurnal Obshchei Khimii,1994,vol. 64,p. 2040 - 2047

30
[ 75-77-4 ]
[ 15118-60-2 ]
[ 5538-51-2 ]
C₂₂H₂₇NO₅Si [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 2571 - 2578

31
[ 15118-60-2 ]
[ 5538-51-2 ]
[ 177653-18-8 ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 2571 - 2578
[2]Synthetic Communications,1997,vol. 27,p. 883 - 895

32
[ 15118-60-2 ]
[ 5538-51-2 ]
4-[4-(2-Acetoxy-benzoylamino)-phenyl]-butyric acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 2571 - 2578

33
[ 100-83-4 ]
[ 5538-51-2 ]
[ 203065-55-8 ]

Yield	Reaction Conditions	Operation in experiment
60.1%	With triethylamine In dichloromethane at 0 - 20℃;	16.1 Step 1: Synthesis of 3-formylphenyl 2-acetoxybenzoate (CD2-L9-CHO) A solution of 3-hydroxybenzaldehyde (HO-L9-CHO, 5.0 g, 40.9 mmol) and triethylamine (12.4 g/14.4 mL, 122.8 mmol) in 50 mL of DCM was added drop-wise to a stirred solution of aspirin acid chloride (freshly prepared from 14.7 g (81.9 mmol) of aspirin by using oxalyl chloride/DMF method) in 100 mL of DCM at 0° C. and the mixture was stirred at RT for overnight when TLC analysis of the mixture indicated completion of the reaction. The mixture was diluted with 100 mL of DCM and washed with water (100 mL) and brine (100 mL), dried over anhydrous Na2SO4 and concentrated in vacuo to give a solid residue which was purified by column chromatography (silica gel 100-200 mesh, eluted with a gradient of EtOAc in petroleum ether and finally with DCM) to afford the title compound as a white solid. Yield: 7.0 g (60.1%); 1H NMR (DMSO-d6, 300 MHz): δ 2.26 (s, 3H), 7.35 (dd, J=8.1, 0.9 Hz, 1H), 7.52 (dt, J=7.8, 0.9 Hz, 1H), 7.58-7.63 (two m, 1H), 7.73 (t, J=8.1 Hz, 1H), 7.77-7.84 (m, 2H), 7.89 (distorted d, J=7.5 Hz, 1H), 8.21 (dd, J=7.8, 1.5 Hz, 1H), 10.05 (s, 1H).
	With triethylamine In diethyl ether 1) r.t., 2 h, 2) reflux, 3 h;
	With triethylamine In dichloromethane at 0 - 20℃; for 2h;

With triethylamine In dichloromethane at 0℃;

Reference： [1]Current Patent Assignee: PIRAMAL ENTERPRISES LIMITED - US2011/263526, 2011, A1 Location in patent: Page/Page column 82
[2]Bowden; Huntington; Powell [European Journal of Medicinal Chemistry, 1998, vol. 32, # 12, p. 987 - 993]
[3]Chiroli, Valerio; Benedini, Francesca; Ongini, Ennio; Del Soldato, Piero [European Journal of Medicinal Chemistry, 2003, vol. 38, # 4, p. 441 - 446]
[4]Hulsman, Niels; Medema, Jan Paul; Bos, Carina; Jongejan, Aldo; Leurs, Rob; Smit, Martine J.; De Esch, Iwan J. P.; Richel, Dick; Wijtmans, Maikel [Journal of Medicinal Chemistry, 2007, vol. 50, # 10, p. 2424 - 2431]

34
[ 5538-51-2 ]
[ 39070-14-9 ]
2-hydroxy-benzoic acid 3-methyl-2-nitro-3<i>H</i>-imidazol-4-ylmethyl ester [ No CAS ]
2-acetoxy-benzoic acid 3-methyl-2-nitro-3<i>H</i>-imidazol-4-ylmethyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 1267 - 1272

35
[ 29331-92-8 ]
[ 5538-51-2 ]
10-(2-acetoxybenzoyloxy)-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

36
[ 5538-51-2 ]
acetylsalicylate sodium [ No CAS ]
[ 1466-82-6 ]

Reference： [1]Patent: DE201325,
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 9,p. 933

37
[ 131230-76-7 ]
[ 5538-51-2 ]
[ 329349-91-9 ]

Reference： [1]Angewandte Chemie - International Edition,2001,vol. 40,p. 207 - 210
Angewandte Chemie,2001,vol. 113,p. 213 - 216

38
[ 86386-73-4 ]
[ 5538-51-2 ]
2-acetoxy-benzoic acid 1-(2,4-difluoro-phenyl)-2-[1,2,4]triazol-1-yl-1-[1,2,4]triazol-1-ylmethyl-ethyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 6255 - 6269

39
[ 5538-51-2 ]
[ 19311-91-2 ]

Reference： [1]Annali di Chimica,1955,vol. 45,p. 205,213

40
[ 122-96-3 ]
[ 5538-51-2 ]
1,4-BIS-[2-(ACETYLSALICYLOYLOXY)ETHYL] PIPERAZINE [ No CAS ]

Reference： [1]Patent: US6369260,2002,B1 .Location in patent: Example 17

41
[ 620-24-6 ]
[ 5538-51-2 ]
[ 287118-98-3 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium carbonate In acetone at 5 - 10℃; for 2h;	1c Example 1c; Preparation of 3-Hydroxymethylphenyl Ester of the 2-Acetoxybenzoic Acid (Compound I-B) in Organic Solvent Miscible With Water 3-hydroxymethylphenol (10 g, 0.08 moles) is dissolved in acetone (50 ml). In the obtained solution potassium carbonate in powder (22.2 g, 0.16 moles) is suspended. To the suspension an acetylsalicylic acid chloride solution (16 g, 0.08 moles) in acetone (50 ml) is added at a temperature of 5°-10° C. under stirring. The mixture is maintained at a temperature in the above mentioned range, under stirring, for 2 hours, then filtered and the solvent evaporated under vacuum. The residue is crystallized from isopropanol. 3-hydroxymethylphenyl ester of the 2-acetoxy-benzoic acid (21.0 g, 0.07 moles, yield 91%) is obtained. [00043] M.P.: 79°-80° C. 1H NMR(CDCl3) δ (ppm): 2.29 (s, 3H); 4.71 (s, 2H); 7.07-8.2 (m, aromatics, 8H).
80%	With sodium hydroxide In dichloromethane; water at 20℃; for 2h;	1a Example 1a; Preparation of 3-Hydroxymethylphenyl Ester of the 2-Acetoxybenzoic Acid (Compound I-B) in Admixture Water-organic Solvent 3-hydroxymethylphenol (25.25 g, 0.2 moles) is dissolved in a 5% hydroxide sodium solution (160 ml). To the so obtained solution an acetylsalicylic acid chloride solution (40.4 g, 0.2 moles) in dichloromethane (50 ml) is added at roam temperature, under stirring. The mixture is maintained at room temperature under stirring for 2 hours and then extracted with dichloromethane (2×100 ml). The organic phase is separated, anhydrified with sodium sulphate and the solvent evaporated under vacuum. The residue is crystallized from a mixture of ethyl acetate and hexane. 3-hydroxymethylphenyl ester of the 2-acetoxybenzoic acid (45.8 g, 0.16 moles, yield 80%) is obtained. [00039] M.P.: 79°-81° C. 1H NMR(CDCl3) δ (ppm): 2.29 (s, 3H); 4.71 (s, 2H); 7.07-8.2 (m, aromatics, 8H).
80%	With triethylamine In toluene at 5 - 10℃; for 2h;	1b Example 1b; Preparation of 3-Hydroxymethylphenyl Ester of the 2-Acetoxybenzoic Acid (Compound I-B) in Organic Solvent Immiscible With Water 3-hydroxymethylphenol (10 g, 0.08 moles) is dissolved in toluene (50 ml) containing triethylamine (9.8 g, 0.1 moles). To the so obtained solution an acetylsalicylic acid chloride solution (16 g, 0.08 moles) in toluene (50 ml) is added at a temperature of 5°-10° C. under stirring. The mixture is maintained at a temperature in the above mentioned range, under stirring for 2 hours, then poured in water and then extracted with dichloromethane (2×100 ml). The organic phase is separated, washed in sequence with a 25% w/v potassium carbonate solution, with water, with a 3% hydrochloric acid solution and lastly with water again, then anhydrified with sodium sulphate and the solvent evaporated under vacuum. The residue is crystallized from isopropanol. 3-hydroxymethylphenyl ester of the 2-acetoxybenzoic acid (45.8 g, 0.16 moles, yield 80%) is obtained. [00041] M.P.: 79°-80° C. 1H NMR(CDCl3) δ (pp): 2.29 (s, 3H); 4.71 (s, 2H); 7.07-8.2 (m, aromatics, 8H).

Reference： [1]Current Patent Assignee: NICOX S.A. - US6696591, 2004, B1 Location in patent: Page column 4
[2]Current Patent Assignee: NICOX S.A. - US6696591, 2004, B1 Location in patent: Page column 4
[3]Current Patent Assignee: NICOX S.A. - US6696591, 2004, B1 Location in patent: Page column 4

42
[ 64-04-0 ]
[ 5538-51-2 ]
[ 346724-83-2 ]

Yield	Reaction Conditions	Operation in experiment
54.9%	With pyridine In benzene at 20℃; for 2h;	2.1 O-Acetylsalicyloyl chloride(0.20g, 1.00mmol) was dissolved in benzene(8mL). Phenethylamine(0.12g, 1.00mmol) and pyridine(0.3mL) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into diluted hydrochloric acid and extracted with ethyl acetate. After the organic layer was washed with water and brine, dried over anhydrous sodium sulfate, the residue obtained by evaporation under reduced pressure was purified by chromatography on silica gel(n-hexane:ethyl acetate=2:1→1:1) to give the title compound(155.5mg, 54.9%) as a white crystal.1H-NMR(CDCl3): δ 2.09(3H, s), 2.92(2H, t, J=6.8Hz), 3.71(2H, q, J=6.8Hz), 6.32(1H, brs),7.07(1H, dd, J=8.4, 1.2Hz), 7.23-7.35(6H, m), 7.44(1H, ddd, J=8.0, 7.6, 1.6Hz), 7.73(1H, dd, J=7.6, 1.6Hz).
54.9%	With pyridine In benzene at 20℃; for 2h;	2.1 (1) 2-Acetoxy-N-(2-phenethyl)benzamide. O-Acetylsalicyloyl chloride(0.20g, 1.00mmol) was dissolved in benzene(8mL). Phenethylamine(0.12g, 1.00mmol) and pyridine(0.3mL) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into diluted hydrochloric acid and extracted with ethyl acetate. After the organic layer was washed with water and brine, dried over anhydrous sodium sulfate, the residue obtained by evaporation under reduced pressure was purified by chromatography on silica gel(n-hexane:ethyl acetate=2:1→1:1) to give the title compound(155.5mg, 54.9%) as a white crystal. 1H-NMR(CDCl3): δ 2.09(3H, s), 2.92(2H, t, J=6.8Hz), 3.71(2H, q, J=6.8Hz), 6.32(1H, brs),7.07(1H, dd, J=8.4, 1.2Hz), 7.23-7.35(6H, m), 7.44(1H, ddd, J=8.0, 7.6, 1.6Hz), 7.73(1H, dd, J=7.6, 1.6Hz).
54.9%	With pyridine In benzene at 20℃; for 2h;	2.1 O-Acetylsalicyloyl chloride(0.20g, 1.00mmol) was dissolved in benzene(8mL). Phenethylamine(0.12g, 1.00mmol) and pyridine(0.3mL) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into diluted hydrochloric acid and extracted with ethyl acetate. After the organic layer was washed with water and brine, dried over anhydrous sodium sulfate, the residue obtained by evaporation under reduced pressure was purified by chromatography on silica gel(n-hexane:ethyl acetate=2:1→1:1) to give the title compound(155.5mg, 54.9%) as a white crystal.1H-NMR(CDCl3): δ 2.09(3H, s), 2.92(2H, t, J=6.8Hz), 3.71(2H, q, J=6.8Hz), 6.32(1H, brs),7.07(1H, dd, J=8.4, 1.2Hz), 7.23-7.35(6H, m), 7.44(1H, ddd, J=8.0, 7.6, 1.6Hz), 7.73(1H, dd, J=7.6, 1.6Hz).

Reference： [1]Current Patent Assignee: INSTITUTE OF MEDICINAL MOLECULAR DESIGN INC - EP1510207, 2005, A1 Location in patent: Page/Page column 114 Current Patent Assignee: INSTITUTE OF MEDICINAL MOLECULAR DESIGN INC - EP1510210, 2005, A1 Location in patent: Page/Page column 114
[2]Current Patent Assignee: INSTITUTE OF MEDICINAL MOLECULAR DESIGN INC - EP1512396, 2005, A1 Location in patent: Page/Page column 112
[3]Current Patent Assignee: INSTITUTE OF MEDICINAL MOLECULAR DESIGN INC; IYAKU BUNSHI SEKKEI KENKYUSHO - EP1514544, 2005, A1 Location in patent: Page/Page column 118

43
[ 978-62-1 ]
[ 5538-51-2 ]
C₂₄H₁₄ClF₆NO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83.4%	With triethylamine; In tetrahydrofuran; at 20℃; for 3.0h;	5-Chloro-2-hydroxy-N-[3,5-bis(trifluoromethyl)phenyl]benzamide(compound of Example 1(1); 0.20g, 0.52mmol) was dissolved in tetrahydrofuran(5mL). O-Acetylsalicyloyl chloride(0.124g, 0.62mmol) and triethylamine(0.2mL, 1.43mmol) were added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into diluted hydrochloric acid and extracted with ethyl acetate. After the ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel(n-hexane:ethyl acetate=3:1), and washed with isopropyl ether/n-hexane under suspension to give the title compound(236.7mg, 83.4percent) as a white powder.1H-NMR(DMSO-d6): delta 2.13(3H, s), 7.29(1H, dd, J=8.4, 1.2Hz), 7.45(1H, td, J=7.8, 1.2Hz), 7.48(1H, d, J=8.7Hz),7.76(1H, td, J=8.4, 1.8Hz), 7.77(1H, dd, J=8.4, 2.4Hz), 7.82(1H, s), 7.94(1H, d, J=2.4Hz), 8.16(1H, dd, J=7.8, 1.5Hz), 8.29(2H, s), 11.12(1H, s).

Reference： [1]Patent: EP1512397,2005,A1 .Location in patent: Page/Page column 78

44
[ 328-74-5 ]
[ 5538-51-2 ]
[ 439144-60-2 ]

Yield	Reaction Conditions	Operation in experiment
84.2%	With pyridine In benzene at 20℃; for 1h;	1 3,5-Bis(trifluoromethyl)aniline(500mg, 2.2mmol) and pyridine(0.5mL) were added to a solution of O-acetylsalicyloyl chloride(345mg, 1.7mmol) in benzene(10mL) under argon atmosphere, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into 2N hydrochloric acid and extracted with ethyl acetate. After the ethyl acetate layer was washed successively with water and brine, dried over anhydrous sodium sulfate, the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel(n-hexane:ethyl acetate=3:1) to give the title compound(570mg, 84.2%) as a white solid. mp 124-125°C.1H-NMR(DMSO-d6): δ 2.36(3H, s), 7.19(1H, dd, J=8.0, 1.2Hz), 7.39(1H, td, J=7.6, 1.2Hz), 7.57(1H, ddd, J=8.0, 7.6, 1.6Hz), 7.65(1H, s), 7.83(1H, dd, J=8.0, 1.6Hz), 8.11(2H, s), 8.31(1H, s).
84.2%	With pyridine In benzene at 20℃; for 1h;	1 3,5-Bis(trifluoromethyl)aniline(500mg, 2.2mmol) and pyridine(0.5mL) were added to a solution of O-acetylsalicyloyl chloride(345mg, 1.7mmol) in benzene(10mL) under argon atmosphere, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into 2N hydrochloric acid and extracted with ethyl acetate. After the ethyl acetate layer was washed successively with water and brine, dried over anhydrous sodium sulfate, the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel(n-hexane:ethyl acetate=3:1) to give the title compound(570mg, 84.2%) as a white solid. mp 124-125°C.1H-NMR(DMSO-d6): δ 2.36(3H, s), 7.19(1H, dd, J=8.0, 1.2Hz), 7.39(1H, td, J=7.6, 1.2Hz), 7.57(1H, ddd, J=8.0, 7.6, 1.6Hz), 7.65(1H, s), 7.83(1H, dd, J=8.0, 1.6Hz), 8.11(2H, s), 8.31(1H, s).
84.2%	With pyridine In benzene at 20℃; for 1h;	1 3,5-Bis(trifluoromethyl)aniline(500mg, 2.2mmol) and pyridine(0.5mL) were added to a solution of O-acetylsalicyloyl chloride(345mg, 1.7mmol) in benzene(10mL) under argon atmosphere, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into 2N hydrochloric acid and extracted with ethyl acetate. After the ethyl acetate layer was washed successively with water and brine, dried over anhydrous sodium sulfate, the residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel(n-hexane:ethyl acetate=3:1) to give the title compound(570mg, 84.2%) as a white solid. mp 124-125°C.1H-NMR(DMSO-d6): δ 2.36(3H, s), 7.19(1H, dd, J=8.0, 1.2Hz), 7.39(1H, td, J=7.6, 1.2Hz), 7.57(1H, ddd, J=8.0, 7.6, 1.6Hz), 7.65(1H, s), 7.83(1H, dd, J=8.0, 1.6Hz), 8.11(2H, s), 8.31(1H, s).

Reference： [1]Current Patent Assignee: INSTITUTE OF MEDICINAL MOLECULAR DESIGN INC - EP1535609, 2005, A1 Location in patent: Page/Page column 72
[2]Current Patent Assignee: INSTITUTE OF MEDICINAL MOLECULAR DESIGN INC - EP1535610, 2005, A1 Location in patent: Page/Page column 71-72
[3]Current Patent Assignee: INSTITUTE OF MEDICINAL MOLECULAR DESIGN INC - EP1555018, 2005, A1 Location in patent: Page/Page column 71

45
[ 50-35-1 ]
[ 5538-51-2 ]
2-acetoxy-N-(2,6-dioxopiperidin-3-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With triethylamine; In chloroform; at 0 - 20℃;	More specifically, 2-acetoxy-N-(2, 6-dioxopiperidin-3-yl) benzamide (24) was prepared as follows. To an ice cold solution of acetylsalicyloylchloride (252 mg) and triethylamine (0. 58 mL) in chloroform (30 mL) was added 3-AMINOGLUTARIDE trifluoroacetate (207 mg). The reaction temperature was allowed to warm to room temperature and stirring was continued overnight. The solvent was removed and recrystallization from ethyl acetate gave compound 24 as white crystals (0.36 g, 98%) : 1H NMR (DMSO-D6) 8 11.00 (s, 1H), 8.73 (d, J = 8. 3 Hz, 1H), 7. 81 (dd, J = 1.6 Hz, J = 7.7 Hz, 1H), 7.72 (m, 1H), 7.54 (m, 1H), 7. 38 (dd, J = 0. 9 Hz, J = 8.1 Hz, 1H), 4.95-4. 82 (m, 1H), 2. 96-2.90 (m, 1H), 2.43 (s, 3H), 2. 18-2. 15 (m, 2H).

Reference： [1]Patent: WO2005/28436,2005,A2 .Location in patent: Page/Page column 42

46
[ 36322-90-4 ]
[ 5538-51-2 ]
4-(2-acetoxybenzoyloxy)-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
442 mg. (4%)	With triethylamine In dichloromethane	1 EXAMPLE 1 EXAMPLE 1 To a well-stirred solution consisting of 6.5 g. (0.019 mole) of 4-hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide (prepared as described in U.S. Pat. No. 3,591,584) dissolved in 200 ml. of methylene chloride containing 2.82 g. (0.028 mole) of triethylamine (3.87 ml.) under a dry nitrogen atmosphere, there was added in a dropwise manner a solution consisting of 5.76 g. (0.029 mole) of 2-acetoxybenzoyl chloride (the product of Preparation A) dissolved in 20 ml. of methylene chloride. The resulting mixture was stirred at room temperature (~20° C.) for a period of 18 hours. At this point, the reaction mixture was successively extracted three times with saturated aqueous sodium bicarbonate solution and one time with saturated aqueous sodium chloride. The organic layer was then dried over anhydrous magnesium sulfate, filtered and evaporated to give a red brown foam. The latter material was then placed on a silica gel column and eluted with methylene chloride/ethyl acetate (4:1 by volume) to effect the desired separation. Upon evaporation of the desired elude, there was obtained crude product material which was thereafter triturated with diethyl ether/ethyl acetate (9:1 by volume) to eventually yield a white solid product. The latter solid was filtered and recrystallized twice from ethyl acetate to finally afford 442 mg. (4%) of pure 4-(2-acetoxybenzoyloxy)-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide, m.p. 170°-173° C. The pure product was further characterized by means of thin layer chromatography and infrared absorption spectra, in addition to elemental analysis. Anal. Calcd. for C24 H19 N3 O7 S: C, 58.41; H, 3.88; N, 8.52. Found: C, 58.20; H, 4.13; N, 8.41.

Reference： [1]Current Patent Assignee: PFIZER INC - US4610982, 1986, A

47
[ 280-13-7 ]
[ 5538-51-2 ]
3-(acetylsalicyloyl)-8-oxa-3-azabicyclo(3.2.1)octane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In benzene;	EXAMPLE 29 3-(Acetylsalicyloyl)-8-Oxa-3-Azabicyclo(3.2.1)Octane SPC8 o-Acetoxybenzoyl chloride (0.1 mole, 19.85 grams) was slowly added to a mixture of 8-oxa-3-azabicyclo(3.2.1)octane (0.1 mole, 11.13 grams) and triethylamine (0.1 mole) in 60 ml of benzene at 20 C. The reaction mixture was stirred 2.5 hours at 25 C. The salt was filtered off and washed with benzene. After removal of benzene, the product was obtained as a viscous liquid which was purified by column chromatography (alumina). Impurities were eluted with ether and the product with methanol to yield the product represented by formula (IX). Analysis for C15 H17 NO4. Calculated: C, 65.44%; H, 6.23%; N, 5.09%. Found: C, 65.55%; H, 6.05%; N, 5.05%.

Reference： [1]Patent: US3953596,1976,A

48
[ 21209-51-8 ]
[ 5538-51-2 ]
[ 852055-89-1 ]

Yield	Reaction Conditions	Operation in experiment
95%	With pyridine; In dichloromethane; at 0 - 20℃; for 48h;	A mixture of N-carbobenzyloxy-L-serine benzyl ester (Z-Ser-OBzl, 23.17 g, 70.34 mmole) and pyridine (30 mL) in anhydrous dichloromethane (500 mL) was cooled in an ice bath while under a nitrogen atmosphere. Acetylsalicyloyl chloride (21.07 g, 106.1 mmole) was added and the mixture was allowed to warm to room temperature and stir over two days. After 48 hours, the mixture was poured into ice-cold 2N hydrochloric acid (400 mL). After mixing, the layers were separated and the dichloromethane fraction was washed water (500 mL), saturated sodium bicarbonate solution (500 mL), water (500 mL), brine (500 mL) and dried over sodium sulfate (25 g). After filtration, concentration under reduced pressure, and drying under high vacuum, the remaining brown solid (47.19 g) was purified by flash chromatography on silica gel (200 g, 0.035-0. 070 mm, 6 nm pore diameter), eluting with hexanes/ethyl acetate (3: 1). After concentration of the product containing fractions under reduced pressure and drying under high vacuum until the weight was constant, the experiment produced the protected acetylsalicylic-L-serine ester SPIB0010101 (32.97 g, 95% yield) as a white solid. 1H NMR (300 MHz, CDC13) : 8 = 7.74 (1H, d, J= 7. 8 Hz), 7.55 (1H, dt, J= 7. 8, 1.5 Hz), 7.33-7. 21 (11H, m), 7.08 (1H, d, J= 7. 5 Hz), 5.68 (1H, d, J= 8. 4 Hz), 5.20 (2H, s), 5.12 (2H, s), 4.77 (1H, m), 4.66 (1H, dd, J= 11.4, 3.3 Hz), 4.57 (1H, dd, J= 11.4, 3.3 Hz), 2.30 (3H, s). 3C NMR (75 MHz, CDC13) : 8 = 169.45, 169.09, 163.68, 163.35, 155.57, 150.77, 135.87, 134.75, 134.07, 131.44, 128.50, 128.43, 128.27, 128.14, 128.04, 125. 92,123. 71, 122.18, 67.83, 67.27, 64.63, 53.55, 21.03

Reference： [1]Patent: WO2005/46575,2005,A2 .Location in patent: Page/Page column 108; 111-112

49
[ 13500-53-3 ]
[ 5538-51-2 ]
[ 852055-91-5 ]

Yield	Reaction Conditions	Operation in experiment
68%	With pyridine; In dichloromethane; at 0 - 20℃; for 72h;	A mixture of N-carbobenzyloxy-L-hydroxyproline benzyl ester (Z-Ser-OBzl, 21.5 g, 60.5 mmole)1 and pyridine (25 mL) in anhydrous dichloromethane (500 mL) was cooled in an ice bath while under a nitrogen atmosphere. Acetylsalicyloyl chloride (13.2 g, 66.6 mmole) was added and the mixture was allowed to warm to room temperature and stir overnight. After 24 hours, additional acetylsalicyloyl chloride (5.0 g, 25.2 mmole) was added and the mixture was allowed to stir overnight. After 48 hours, the mixture was poured into ice-cold 1N hydrochloric acid (500 mL). After mixing, the layers were separated and the dichloromethane fraction was washed with water (500 mL), saturated sodium bicarbonate solution (500 mL), water (500 mL), brine (500 mL) and dried over sodium sulfate (25 g). After filtration, concentration under reduced pressure, and drying under high vacuum, the remaining yellow oil (40.7 g) was purified by flash chromatography on silica gel (460 g, 0. 03 5-0. 070 mm, 6 nm pore diameter), eluting with heptane/ethyl acetate (3: 1). After concentration of the product containing fractions under reduced pressure and drying under high vacuum until the weight was constant, the experiment produced the protected acetylsalicylic-L-hydroxyproline ester SPIB0010301 (21.31 g, 68% yield) as a colorless oil. SPIB0010301 'H NMR (300 MHz, CDC13) : 8 = 7.92 (1H, d, J= 7.8 Hz), 7.56 (1H, t, J= 7. 8 Hz), 7.34- 7.21 (1OH, m), 7.09 (1H, d, J= 7. 8 Hz), 5.48 (1H, s), 5.21 (2H, m), 5.03 (2H, d, J=15 Hz), 4.57 (1H, m), 3.85 (2H, m), 2.53 (1H, m), 2.28 (4H, m). 13C NMR (75 MHz, CDC13) : 8 = 171.72, 171.49, 169.25, 163.47, 163.30, 154.52, 153.93, 150.54, 136.05, 135.94, 135.21, 135.00, 134.17, 134.12, 128.43, 128.32, 128.28, 128.20, 128.05, 127.98, 127.94, 127.79, 125.89, 123.70, 122.46, 122.38, 73.24, 72.59, 67.33, 67.11, 66.97, 58.02, 57.69, 52.47, 52.15, 36.74, 35.65, 20.90

Reference： [1]Patent: WO2005/46575,2005,A2 .Location in patent: Page/Page column 108; 113-114

50
[ 84500-41-4 ]
[ 5538-51-2 ]
[ 852055-87-9 ]

Yield	Reaction Conditions	Operation in experiment
88%	With pyridine; In dichloromethane; at 0 - 20℃; for 24h;	A mixture of N-carbobenzyloxy-L-threonine benzyl ester (Z-Thr-OBzl, 21.77 g, 63.40 mmole) and pyridine (25 mL) in anhydrous dichloromethane (500 mL) was cooled in an ice bath while under a nitrogen atmosphere. Acetylsalicyloyl chloride (17.63 g, 88.76 mmole) was added and the mixture was allowed to warm to room temperature and stir overnight. After 24 hours, the mixture was poured into ice-cold 2N hydrochloric acid (400 mL). After mixing, the layers were separated and the dichloromethane fraction was washed with water (500 mL), saturated sodium bicarbonate solution (500 mL), water (500 mL), brine (500 mL) and dried over sodium sulfate (25 g). After filtration, concentration under reduced pressure, and drying under high vacuum, the remaining yellow oil (35.43 g) was purified by flash chromatography on silica gel (300 g, 0.035- 0.070 mm, 6 nm pore diameter), eluting with hexanes/ethyl acetate (3: 1). After concentration of the product containing fractions under reduced pressure and drying under high vacuum until the weight was constant, the experiment produced the protected acetylsalicylic-L-threonine ester SPIB0010201 (28.1 g, 88% yield) as a colorless oil. IH NMR (300 MHz, CDC13) : 5 = 7.74 (1H, d, J= 7. 5 Hz), 7.51 (1H, dt, J= 7. 5,1. 5 Hz), 7. 34-7. 17 (lah, m), 7.06 (1H, d, J= 7. 2 Hz), 5.62 (2H, m), 5.13 (4H, m), 4.65 (1H, dd, J= 9.6, 2.4 Hz), 2.29 (3H, s), 1. 38 (3H, d, J= 6.6 Hz). 3C NMR (75 MHz, CDC13) : 8 = 169.35, 169.22, 162.73, 156.26, 150.41, 135.79, 134.67, 133.77, 131.24, 128.35, 128.24, 128.08, 127.95, 125.78, 123.51, 122.61, 71.22, 67.72, 67.26, 57.64, 20.98, 16. 88.

Reference： [1]Patent: WO2005/46575,2005,A2 .Location in patent: Page/Page column 108-110

51
[ 99171-11-6 ]
[ 5538-51-2 ]
[ 1109286-02-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	With triethylamine; In tetrahydrofuran; at 20℃;	7.2 Synthesis of 2-(5-(methylthio)thiazol-2-ylcarbamoyl)phenyl acetate (69) Under nitrogen a solution of acetylsalicyloyl chloride (1.237 g, 6.20 mmol, 1.3 eq) in THF (40 mL) was added to a stirred solution of 5-(methylthio)thiazol-2-amine? (700.0 mg, 4.79 mmol, 1.0 eq) in dry THF (mL). This was followed by the addition of triethylamine (0.67 mL, 4.79 mmol, 1.0 eq). The reaction mixture was stirred at room temperature and monitored by TLC. After two hours, reaction was filtered through sintered funnel and solvent removed in vacuo. The crude product was dissolved in EtOAc (150 mL) and washed twice each with 1M HCl and saturated aq. sodium hydrogen carbonate solutions. The organic fraction was dried over MgSO4 followed the removal of solvent. Flash column chromatography yielded the pure product 69 (1.450 g, 98percent) as a solid. Data for 69: m.p.=145-147° C.; TLC (silica gel) Rf=0.36 (Hex:EtOAc, 1:1); 1H-NMR (DMSO-d, 400 MHz), 2.23 (3H, s, CH3), 2.47 (3H, s, CH3), 7.28 (1H, dd, J=1.0, 8.0 Hz, ArH), 7.41 (1H, td, J=1.0, 7.6 Hz, ArH), 7.56 (1H, s, CH), 7.63 (1H, td, J=1.7, 8.0 Hz, ArH), 7.78 (1H, dd, J=1.7, 7.6 Hz, ArH), 12.70 (1H, s, NH); 13C-NMR (DMSO-d, 100 MHz), 21.1, 22.0, 123.7, 124.6, 126.2, 126.9, 130.0, 133.1, 141.6, 148.9, 160.0, 164.5, 169.2; m/z (CI) 309 (MH-); HRMS, found 309.03654, C13H13N2O3S2 requires 309.03677, (-0.8 ppm).
98%	With triethylamine; In tetrahydrofuran; at 20℃; for 2.0h;Inert atmosphere;	Under nitrogen a solution of acetylsalicyloyl chloride (1.24 g, 6.20 mmol, 1.3 eq) in THF (40 mL) was added to a stirred solution of 5-(methylthio)thiazol-2-amine 514 (700.0 mg, 4.79 mmol, 1.0 eq) in dry THF (5 mL).This was followed by the addition of triethylamine (0.67 mL, 4.79 mmol, 1.0 eq).The reaction mixture was stirred at room temperature and monitored by TLC. After two hours, reaction was filtered through sintered funnel and solvent removed in vacuo.The crude product was dissolved in EtOAc (150 mL) and washed twice each with 1M HCl and saturated aq. sodium hydrogen carbonate solutions.The organic fraction was dried over MgSO4 followed the removal of solvent.Flash column chromatography yielded the pure product 518 (1.450 g, 98percent) as a solid. Data for 518: m.p.=145-147° C.; TLC (silica gel) Rf=0.36 (Hex:EtOAc, 1:1);1H-NMR (DMSO-d, 400 MHz), 2.23 (3H, s, CH3), 2.47 (3H, s, CH3), 7.28 (1H, dd, J=1.0, 8.0 Hz, ArH), 7.41 (1H, td, J=1.0, 7.6 Hz, ArH), 7.56 (1H, s, CH), 7.63 (1H, td, J=1.7, 8.0 Hz, ArH), 7.78 (1H, dd, J=1.7, 7.6 Hz, ArH), 12.70 (1H, s, NH); 13C-NMR (DMSO-d, 100 MHz), 21.1, 22.0, 123.7, 124.6, 126.2, 126.9, 130.0, 133.1, 141.6, 148.9, 160.0, 164.5, 169.2; m/z (CI) 309 (MH+); HRMS. found 309.03654, C13H13N2O3S2 requires 309.03677, (-0.8 ppm).

Reference： [1]Patent: US2009/36467,2009,A1 .Location in patent: Page/Page column 79
[2]Patent: US2012/108591,2012,A1 .Location in patent: Page/Page column 34
[3]Journal of Medicinal Chemistry,2011,vol. 54,p. 4119 - 4132

52
[ 75-07-0 ]
[ 5538-51-2 ]
[ 1144618-76-7 ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: O-acetylsalicyloyl chloride With zinc(II) chloride In dichloromethane for 0.25h; Stage #2: acetaldehyde In dichloromethane at -15 - 20℃; for 18h;	23 Example 231- [ (4-{ [3- (nitrooxy) propyl] thio}benzoyl) oxy] ethyl 2- (acetyloxy) Benzoate: compound (24)1- (chloroethyl) 2- (acetyloxy) benzoateTo a solution of 2- (chlorocarbonyl) phenyl acetate (10.0 g, 50.35 mmol) in dry CH2CI2 (100 mL) , kept under inert atmosphere, ZnCl2 (0.14 g, 1.01 mmol) was added. After 15 min the reaction mixture was cooled at -15 °C and a solution of CH3CHO (2.8 mL, 50.35 mmol) in dry CH2Cl2 (30 mL) was slowly added. Then the reaction was allowed to reach room temperature and stirred for 18 hours. The mixture was washed with H2O (100 mL) and a saturated solution of NaHCO3 (100 mL) , dried with MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (PE/EtOAc 9/1 v/v) to give the title compound (7.84 g) as a colourless oil. Yield 64 %. TLC: Rf = 0.35 PE/EtOAc 90/10 v/v 1H-NMR (CDCl3) δ 1.89 (3H, d) , 2.37 (3H, s), 6.73 (1H, q) , 7.13 (1H, d, Arom) , 7.34 (1H, t, Arom) , 7.60 (1H, t, Arom) , 8.04 (1H, d, Arom) . 13C-NMR (CDCl3) δ 21.0, 25.3, 81.1, 122.1, 124.0, 126.1, 132.0, 134.7, 151.0, 162.0, 169.5. MS (CI) m/z 242/244 (M+l)+.
64%	With zinc(II) chloride In dichloromethane at -15 - 20℃; Inert atmosphere;
23%	Stage #1: O-acetylsalicyloyl chloride With zinc(II) chloride In dichloromethane at 20℃; for 0.25h; Stage #2: acetaldehyde In dichloromethane at -15 - 20℃; for 12.4167h;	Steps 1 and 2: Synthesis of (2S)-1-chloroethyl 2-(6-methoxynaphthalen-2-yl)propanoate (D²-2a) General procedure: To a stirred solution of naproxen (D2-C(=O)OH, 5.0 g, 21.71 mmol) in dichloromethane (50 mL) at 0°C under nitrogen was added oxalyl chloride (5.51 mL, 65.14 mmol) followed by catalytic amount of dry DMF (2 drops) and the mixture was then stirred at room temperature for 2.5 h and concentrated. Intermediate naproxen acid chloride D2-1 was taken in dichloromethane (30 mL), added zinc chloride (0.06 g, 0.43 mmol) as a solid and stirred vigorously at room temperature for 15 min. Reaction flask was then cooled at -15 °C and a solution of acetaldehyde (Aa, 1.22 mL, 21.71 mmol) in dichloromethane (20 mL) was added drop wise. After 25 min of stirring, cooling bath was removed and continued stirring at room temperature for 12 h. Reaction mixture was diluted with dichloromethane (30 mL) and washed with water (50 mL), saturated NaHCO3 solution (50 mL) and brine (50 mL). Organic layer was dried over MgSO4 and concentrated. Crude compound was purified by silica gel (200-400 mesh) column chromatography using 5 % EtOAc / Pet. ether to give the corresponding chloro intermediate D2-2a (5.10 g, 80.0 %) as yellow oil.

3.00 g

With zinc(II) chloride In dichloromethane at -15 - 20℃; for 16h; Inert atmosphere;

1.2 Steps 1 and 2: Synthesis of 1-chloroethyl 2-acetoxybenzoate D1-R1-CI Steps 1 and 2: Synthesis of 1-chloroethyl 2-acetoxybenzoate D1-R1-CI To a stirred suspension of aspirin (40.00 g, 222.22 mmol) in dry DCM (250 mL) were added oxalyl chloride (22.80 mL, 266.56 mmol) and a catalytic amount of DMF (4-5 drops) at RT under nitrogen. The resulting mixture was stirred at RT for 3 hours and concentrated to afford aspirin acid chloride (quantitative) as pale yellow oil. To a stirred solution of the acid chloride (11.00 g, 55.55 mmol) in dry DCM (100 mL) was added a catalytic amount of zinc chloride (0.15 g, 1.11 mmol) followed by drop wise addition of acetaldehyde (3.10 mL, 55.55 mmol) at -15 °C under nitrogen. The reaction mixture was stirred at RT for 16 hours and concentrated. The residue was dissolved in ethyl acetate (100 mL), washed successively with water (3 x 100 mL), saturated sodium bicarbonate solution (3 x 100 mL) and brine (2 x 100 mL), dried over sodium sulfate and concentrated. The crude compound was purified by silica gel (200-400 mesh) column chromatography using a gradient of 5 to 15 % ethyl acetate in petroleum ether as eluent to afford the desired compound D1-R1-CI (3.00 g, 23.0 %) as colorless oil. 1H NMR (CDCI3, 300 MHz): δ 1.91 (d, J = 5.7 Hz, 3H), 2.39 (s, 3H), 6.75 (q, J = 5.7, 11.7 Hz, 1 H), 7.36 (t, J = 7.8 Hz, 1 H), 7.60 - 7.64 (m, 1 H), 8.00 (dd, J = 1.2, 7.8 Hz, 1 H)

Reference： [1]Current Patent Assignee: NICOX S.A. - WO2009/49961, 2009, A2 Location in patent: Page/Page column 57-58
[2]Location in patent: experimental part Lazzarato, Loretta; Donnola, Monica; Rolando, Barbara; Chegaev, Konstantin; Marini, Elisabetta; Cena, Clara; Di Stilo, Antonella; Fruttero, Roberta; Biondi, Stefano; Ongini, Ennio; Gasco, Alberto [Journal of Medicinal Chemistry, 2009, vol. 52, # 16, p. 5058 - 5068]
[3]Gund, Machhindra; Gaikwad, Parikshit; Borhade, Namdev; Burhan, Aslam; Desai, Dattatraya C.; Sharma, Ankur; Dhiman, Mini; Patil, Mohan; Sheikh, Javed; Thakre, Gajanan; Tipparam, Santhosh G.; Sharma, Somesh; Nemmani, Kumar V.S.; Satyam, Apparao [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 24, p. 5587 - 5592]
[4]Current Patent Assignee: SATYAM, Apparao - WO2014/111957, 2014, A1 Location in patent: Page/Page column 74

53
[ 108-01-0 ]
[ 64-19-7 ]
[ 5538-51-2 ]
dimethylaminoethyl salicylate acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: 2-(N,N-dimethylamino)ethanol; O-acetylsalicyloyl chloride With triethylamine In chloroform at 0 - 20℃; for 3h; Stage #2: acetic acid In chloroform	2 2. Synthesis of Dimethylaminoethyl Salicylate Acetate 19.9 g (0.1 mol) of acetylsalicyl chloride was dissolved in 100 ml of chloroform. The mixture was cooled to 0 ° C. To the reaction mixture was added 15 ml of triethylamine and 8.9 g (0.1 mol) of dimethylaminoethanol. The mixture was stirred at room temperature for 3 hours. The solvent is evaporated. The residue was dissolved in 300 ml of methanol and 200 ml of a 5% aqueous solution of sodium bicarbonate was added to the reaction mixture. The mixture was refluxed for 2 hours. Dry the mixture. The residue was stirred with 300 ml of methanol. The solid was removed by filtration and washed with methanol. The solution was evaporated to dryness and the residue was dissolved in 200 ml of chloroform. The reaction mixture was stirred with 6 g of acetic acid. The solid was removed by filtration. The reaction mixture was stirred and 6 g of acetic acid was added. The organic phase is evaporated. After drying, 23 g of a hygroscopic product was obtained in a yield of 88%.
88%	Stage #1: 2-(N,N-dimethylamino)ethanol; O-acetylsalicyloyl chloride With triethylamine In chloroform at 0 - 20℃; for 3h; Stage #2: With methanol; water; sodium hydrogencarbonate for 2h; Heating / reflux; Stage #3: acetic acid In chloroform	2 2. Preparation of dimethylaminoethyl salicylate.AcOH[41] 19.9 g (0.1 mol) of acetylsalicyl chloride was dissolved in 100 ml of chloroform.The mixture was cooled to 0°C. 15 ml of triethylamine and 8.9 g (0.1 mol) of dimethylaminoethanol were added into the reaction mixture. The mixture is stirred for 3 hours at RT. The solvents are evaporated off. The residue is dissolved in methanol (300ml), 5% sodium bicarbonate (200 ml) is added into the reaction mixture. The mixture is refluxed for 2 hr. The mixture is evaporated to dryness. Methanol (300 ml) is added into the residue with stirring. Solid is removed by filtration and washed with methanol. The solution is evaporated to dryness and the residue is dissolved in chloroform (200 ml). 6 g of acetic acid is added into the reaction mixture with stirring. Some solid is removed by filtration. Another 6 g of acetic acid is added into the reaction mixture with stirring. The organic solution was evaporated off. After drying, it yielded 23 g of the desired product (88%). Hygroscopic product; Solubility in water: 350 mg/ml; Elementary analysis: C 3H 9NO5; MW: 269.29. Calculated % C: 57.98; H: 7.11; N: 5.20; O: 29.71; Found % C: 57.96; H: 7.13; N: 5.17; O: 29.74. 1H-NMR (400 MHz, CDCl3): δ: 2.21 (s, 3H), 2.90 (s, 6H), 3.70(m, 2H), 4.69 (t, 2H), 4.9 (b, IH), 6.74 (b, IH), 6.84 (m, IH), 6.93 (b, IH), 6.98 (b, 1H),7.3O (b, IH).

Reference： [1]Current Patent Assignee: TECHFIELDS BIOCHEM CO. LTD - CN105439877, 2016, A Location in patent: Paragraph 0067; 0068
[2]Current Patent Assignee: TECHFIELDS BIOCHEM CO. LTD - WO2008/12603, 2008, A1 Location in patent: Page/Page column 15-16

54
[ 169260-97-3 ]
[ 5538-51-2 ]
[ 1215310-13-6 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane;	Examples of the invention, compounds (1) and (2), may be synthesized by the method described in the following reaction scheme. 2-Amino-5-trifluoromethyl-thiazole was prepared by a modification of the procedure of Laduron et al. J. Fluorine Chem. 1995, 73, 83-86. Coupling of o-acetylsalicyloyl choride and <strong>[169260-97-3]2-Amino-5-trifluoromethylthiazole</strong> in the presence of a suitable base, including tertiary amines like triethylamine, in a suitable inert solvent like dichloromethane, at about 0 0C to about ambient room temperature, affords compound (1). Hydrolysis of the acetyl moiety of compound (1) with dilute hydrochoric acid at room temperature to about 50 0C yields compound (2).

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 4119 - 4132
[2]Patent: WO2010/132404,2010,A1 .Location in patent: Page/Page column 129-130

55
[ 349-49-5 ]
[ 5538-51-2 ]
[ 1254956-24-5 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane;	Further examples of the invention, compounds (3) and (4), may be synthesized via the synthetic pathway outlined in the scheme below, using commercially available 2-amino- 4-trifluoromethylthiazole as a starting material.

Reference： [1]Patent: WO2010/132404,2010,A1 .Location in patent: Page/Page column 131

56
[ 101080-15-3 ]
[ 5538-51-2 ]
[ 1309612-60-9 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 4119 - 4132

57
[ 5538-51-2 ]
[ 73040-66-1 ]
C₁₈H₁₃ClN₂O₃S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 4119 - 4132

58
[ 1892-29-1 ]
[ 5538-51-2 ]
2-((2-hydroxyethyl)disulfanyl)ethyl 2-acetoxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46.6%	With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;	2.1 Step 1: Synthesis of 2-((2-hydroxyethyl)disulfanyl)ethyl 2-acetoxybenzoate (CD2-L1-OH) A solution of aspirin acid chloride (CD2-CI, 7.0 g, 35.3 mmol, freshly prepared from aspirin by using oxalyl chloride/DMF/DCM method) in 20 mL of DCM was added drop-wise to a stirred solution of 2-hydroxyethyl disulfide (HO-L1-OH, 10.9 g, 70.5 mmol) and Triethylamine (7.35 mL, 52.89 mmol) in 50 mL of DCM at 0° C. under nitrogen atmosphere and the mixture was stirred at RT for overnight, when TLC analysis of the mixture indicated completion of the reaction. The mixture was diluted with 25 mL of water and 100 mL of DCM. The organic layer was separated and washed with aqueous sodium bicarbonate (2100 mL) and brine (1100 mL), dried over Na2SO4 and concentrated in vacuo to give 10.0 g of crude oil which was purified by column chromatography (225.0 g of silica gel, 150-300 mesh, eluted with 5-30% ethyl acetate in petroleum ether) to afford the title compound (CD2-L1-OH) as yellow oil. Yield: 5.2 g (46.6%); 1H NMR (CDCl3, 300 MHz): δ 2.26 (bt, J=4.2 Hz, 1H), 2.38 (s, 3H), 2.90 (t, J=6.0 Hz, 2H), 3.05 (t, J=6.6 Hz, 2H), 3.69 (distorted q or m, 2H), 4.57 (t, J=6.6 Hz, 2H), 7.13 (dd, J=8.1, 0.9 Hz, 1H), 7.34 (dt, J=7.8 Hz, 1H), 7.60 (dt, J=7.8, 1.5 Hz, 1H), 8.06 (dd, J=7.8, 1.5 Hz); MS m/z: 339.0 [M+Na]+.

Reference： [1]Current Patent Assignee: PIRAMAL ENTERPRISES LIMITED - US2011/263526, 2011, A1 Location in patent: Page/Page column 77

59
[ 626-18-6 ]
[ 5538-51-2 ]
[ 1345092-35-4 ]

Yield	Reaction Conditions	Operation in experiment
38.2%	With triethylamine; In dichloromethane; at 0 - 20℃; for 8h;	Step 1: Synthesis of 3-(hydroxymethyl)benzyl 2-acetoxybenzoate (CD2-L10-OH) A solution of aspirin acid chloride (3.0 g, 16.7 mmol, freshly prepared from aspirin using oxalyl chloride/DMF method) in dichloromethane (15 mL) was added to a stirred solution of 1,3-benzenedimethanol (HO-L10-OH, 2.3 g, 16.6 mmol) and triethylamine (6.96 mL, 49.9 mmol) in dichloromethane (12 mL) at 0 C. The mixture was stirred at RT for 8 h when TLC analysis of the mixture indicated completion of the reaction. The mixture was concentrated and the residue was partitioned between ethyl acetate (100 mL) and water (50 mL). The organic layer was separated, washed with brine (1*50 mL), dried over anhydrous Na2SO4 and concentrated in vacuo to give the crude oily residue which was purified by column chromatography (silica gel, 150.0 g, 200-400 mesh, 30% EtOAc in hexane) to afford the title compound as colorless oil. Yield: 1.9 g (38.2%); 1H NMR (CDCl3, 300 MHz): delta 1.99 (t, J=5.7 Hz, 1H), 2.14 (s, 3H), 4.73 (d, J=5.4 Hz, 2H), 5.33 (s, 2H), 7.10 (d, J=8.1 Hz, 1H), 7.30-7.43 (m, 5H), 7.58 (dt, J=7.8, 1.5 Hz, 1H), 8.08 (dd, J=7.8, 1.5 Hz, 1H); MS m/z: 301.1 [M+H]+, 323.1 [M+Na]+.

Reference： [1]Patent: US2011/263526,2011,A1 .Location in patent: Page/Page column 83

60
[ 1147350-75-1 ]
[ 5538-51-2 ]
[ 1312440-98-4 ]

Yield	Reaction Conditions	Operation in experiment
56%	Stage #1: 2-Oxoclopidogrel With triethylamine In tetrahydrofuran for 0.166667h; Stage #2: O-acetylsalicyloyl chloride In tetrahydrofuran at 0 - 25℃; for 4h;
56%	With triethylamine In tetrahydrofuran at 20℃; for 24h;	9 Example 9 (S)-methyl 2-(2-(2-acetoxybenzoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate (I-5) [Show Image] 338 mg of (2S)-methyl 2-(2-chlorophenyl)-2-(2-oxo-7,7a-dihydrothieno[3.2-c]pyridin-5(2H, 4H, 6H)-yl)-acetate (IV-1) was dissolved in 15 ml of tetrahydrofuran, 0.83 ml of triethylamine was added dropwise and stirred for 10 minutes, and then 600 mg of acetylsalicylic chloride was added and stirred at room temperature for 24 hrs. The reaction solution was poured into saturated aqueous NaHCO3 solution (20 ml), extracted with ethyl acetate (50 ml x 3), concentrated, evaporated, and subjected to flash column chromatography (petroleum ether:ethyl acetate=5:1), to obtain (S)-methyl 2-(2-(2-acetoxybenzoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate (1-5) (280 mg). Yield: 56%, ee = 96.1% (chiral HPLC analysis conditions: Chiralpak IC 4.6 mm x 250 mm; column temperature: 25°C; mobile phase: 85% n-hexane/15% tetrahydrofuran/0.1% diethylamine; flow rate: 0.5 ml/min; and detection wavelength: UV 254 nm), [α]D20 = + 14.00°(c 0.50, CHCl3); 1H-NMR (300 MHz, CDCl3) δ 2.34 (s, 3 H), 2.79-2.81 (m, 2 H), 2.90-2.93 (m, 2 H), 3.54-3.66 (m, 2 H), 3.72 (s, 3 H), 4.93 (s, 1 H), 6.37 (s, 1 H), 7.14-7.36 (m, 4 H), 7.39-8.15 (m, 4 H); 13C-NMR (75 MHz, CDCl3) δ 20.93, 24.93, 48.04, 50.12, 52.12, 67.65, 112.61, 117.34, 118.97, 121.66, 124.09, 126.14, 127.12, 129.35, 129.45, 129.79, 129.92, 130.71, 132.12, 133.54, 134.71, 135.73, 149.32, 151.12, 161.32, 169.47, 171.17; ESI-MS m/z 500 [M+H]+, 522 [M+Na]+; HRMS Calcd for C25H23NO6SCl [M+H]+ m/z 500.0931, found 500.0935.
56%	Stage #1: 2-Oxoclopidogrel With triethylamine In tetrahydrofuran for 0.166667h; Stage #2: O-acetylsalicyloyl chloride In tetrahydrofuran at 20℃; for 24h;	9 (S)-methyl 2-(2-(2-acetoxybenzoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate (I-5) Example 9 (S)-methyl 2-(2-(2-acetoxybenzoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate (I-5) 338 mg of (2S)-methyl 2-(2-chlorophenyl)-2-(2-oxo-7,7a-dihydrothieno[3,2-c]pyridin-5(2H,4H,6H)-yl)-acetate (IV-1) was dissolved in 15 ml of tetrahydrofuran, 0.83 ml of triethylamine was added dropwise and stirred for 10 minutes, and then 600 mg of acetylsalicylic chloride was added and stirred at room temperature for 24 hrs. The reaction solution was poured into saturated aqueous NaHCO3 solution (20 ml), extracted with ethyl acetate (50 ml3), concentrated, evaporated, and subjected to flash column chromatography (petroleum ether:ethyl acetate=5:1), to obtain (S)-methyl 2-(2-(2-acetoxybenzoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate (I-5) (280 mg). Yield: 56%, ee=96.1% (chiral HPLC analysis conditions: Chiralpak IC 4.6 mm250 mm; column temperature: 25° C.; mobile phase: 85% n-hexane/15% tetrahydrofuran/0.1% diethylamine; flow rate: 0.5 ml/min; and detection wavelength: UV 254 nm), [α]D20=+14.00° (c 0.50, CHCl3); 1H-NMR (300 MHz, CDCl3) δ 2.34 (s, 3H), 2.79-2.81 (m, 2H), 2.90-2.93 (m, 2H), 3.54-3.66 (m, 2H), 3.72 (s, 3H), 4.93 (s, 1H), 6.37 (s, 1H), 7.14-7.36 (m, 4H), 7.39-8.15 (m, 4H); 13C-NMR (75 MHz, CDCl3) δ 20.93, 24.93, 48.04, 50.12, 52.12, 67.65, 112.61, 117.34, 118.97, 121.66, 124.09, 126.14, 127.12, 129.35, 129.45, 129.79, 129.92, 130.71, 132.12, 133.54, 134.71, 135.73, 149.32, 151.12, 161.32, 169.47, 171.17; ESI-MS m/z 500 [M+H]+, 522 [M+Na]+; HRMS Calcd for C25H23NO6SCl [M+H]+ m/z 500.0931, found 500.0935.

Reference： [1]Location in patent: experimental part Shan, Jiaqi; Zhang, Boyu; Zhu, Yaoqiu; Jiao, Bo; Zheng, Weiyi; Qi, Xiaowei; Gong, Yanchun; Yuan, Fang; Lv, Fusheng; Sun, Hongbin [Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3342 - 3352]
[2]Current Patent Assignee: JILIN YATAI (GROUP) CO., LTD. - EP2532668, 2012, A1 Location in patent: Page/Page column 10
[3]Current Patent Assignee: JILIN YATAI (GROUP) CO., LTD. - US2013/165476, 2013, A1 Location in patent: Paragraph 0103; 0104

61
[ 124-20-9 ]
[ 76-05-1 ]
[ 5538-51-2 ]
C₂₁H₂₇N₃O₄*C₂HF₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: N-(3-aminopropyl)-1,4-diaminobutane; O-acetylsalicyloyl chloride With triethylamine In dichloromethane at -20 - 20℃; for 5h; Inert atmosphere; Stage #2: trifluoroacetic acid	A stirred solution of2-acetylsalicylic acid (1.00 g, 5.55 mmol) in dry CH2Cl2 (400mL) at 0 °C under nitrogen was treated, dropwise, with oxalyl chloride (554µL, 6.38 mmol) followed by DMF (100 µL, cat.). After 1 h the reaction waswarmed to room temperature and stirred for 18 h and then reaction mixture wasconcentrated in vacuo to afford2-acetylsalicyloyl chloride as a cream solid which was used in the followingprocedure without purification. A magnetically stirred solution of spermidine(100 mg, 0.69 mmol) and anhydrous triethylamine (575 µL, 4.10 mmol) in CH2Cl2(5 mL) under nitrogen at - 20 °C was treated, dropwise, with a solution of2-acetylsalicyloyl chloride (287 mg, 1.45 mmol) in CH2Cl2(5 mL). The ensuing mixture was stirred for 1 h at - 20 °C and a further 4 h at room temperature before being treated with NaHCO3 (5mL of a saturated aqueous solution) then extracted with CH2Cl2 (3 × 15 mL). The combined organic extracts weredried (Na2SO4), filtered and concentrated under reducedpressure and the crude residue was purified by semi-preparative reversed phaseC18 HPLC using the isolation conditions described above to givecompound 17 (22.0 mg, 8% yield) as a colourless oil.

Reference： [1]Choomuenwai, Vanida; Schwartz, Brett D.; Beattie, Karren D.; Andrews, Katherine T.; Khokhar, Shahan; Davis, Rohan A. [Tetrahedron Letters, 2013, vol. 54, # 38, p. 5188 - 5191]

62
[ 537-42-8 ]
[ 5538-51-2 ]
[ 1511857-25-2 ]

Yield	Reaction Conditions	Operation in experiment
96%	With triethylamine; In dichloromethane; at 0 - 20℃; for 2h;	Di-methylated resveratrol (<strong>[537-42-8]pterostilbene</strong>; Pt) was reacted with 1.2 equivalents of acetylsalicyloyl chloride under basic conditions to generate <strong>[537-42-8]pterostilbene</strong> aspirinate (PAS; yield: 96%). The structure of PAS was determined by 1H, 13C, and 2D (HMQC and HMBC) NMR and MS analysis. PAS: white solid; 1H NMR (700 MHz, CDCl3) delta 6.66 (2H, t, J=2.0 Hz, H-2/6), 6.39 (1H, t, J=2.0 Hz, H-4), 6.99 (1H, d, J=16.1 Hz, H-7), 7.07 (1H, d, J=16.1 Hz, H-8), 7.53 (2H, d, J=8.4 Hz, H-10/14), 7.16 (2H, d, J=8.4 Hz, H-11/13), 7.17 (1H, d, J=8.0 Hz, H-4?), 7.62 (1H, dt, J=8.0, 1.4 Hz, H-5?), 7.37 (1H, t, J=8.0 Hz, H-6?), 8.21 (1H, dd, J=8.0, 1.4 Hz, H-7?), 2.30 (3H, s, CH3C?O), and 3.81 (6H, s, OMe-3/5); 13C NMR (175 MHz, CDCl3) delta 139.2 (s, C-1), 104.6 (d, C-2/6), 161.0 (s, C-3/5), 100.1 (d, C-4), 129.1 (d, C-7), 128.1 (d, C-8), 135.3 (s, C-9), 127.7 (d, C-10/14), 121.9 (d, C-11/13), 150.0 (s, C-12), 163.0 (s, C-1?), 122.5 (s, C-2?), 151.2 (s, C-3?), 124.1 (d, C-4?), 134.7 (d, C-5?), 126.3 (d, C-6?), 132.3 (d, C-7?), 169.8 (s, CH3CC?O), 21.1 (q, CH3C?O), and 55.4 (q, OMe-3/5); positive APCIMS, m/z 419 [M+H]+.

Reference： [1]Patent: US2013/338120,2013,A1 .Location in patent: Paragraph 0180; 0181; 0182
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 6494 - 6506

63
[ 19798-77-7 ]
[ 5538-51-2 ]
N-(3-chloropyridin-4-yl)-2-hydroxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of substituted acetylsalicyloyl chlorides (0.022 mol) in anhydrous chloroform (100 mL) was added triethylamine (0.023 mol) at 4 C. After the mixture was stirred for 5-15 min and then substituted 4-amino pyridinewas added portion wise in the ice bath. After warmed to room temperature, the solution was stirred for 24-48 h and then quenched by 1 mL of 1 M hydrochloric acid. The reaction mixture was extracted with 10 % hydrochloric acid (50, 30and 30 mL) and the combined aqueous was basified to pH 7-9 with cooled saturated sodium bicarbonate solution. The yellow precipitation was filtered producing the crude products. After recrystallized in ethanol, the products were isolated as pure form in more than 85 % yields.

Reference： [1]Asian Journal of Chemistry,2014,vol. 26,p. 7269 - 7275

64
[ 1990-90-5 ]
[ 5538-51-2 ]
N-(3-methylpyridin-4-yl)-2-hydroxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of substituted acetylsalicyloyl chlorides (0.022 mol) in anhydrous chloroform (100 mL) was added triethylamine (0.023 mol) at 4 C. After the mixture was stirred for 5-15 min and then substituted 4-amino pyridinewas added portion wise in the ice bath. After warmed to room temperature, the solution was stirred for 24-48 h and then quenched by 1 mL of 1 M hydrochloric acid. The reaction mixture was extracted with 10 % hydrochloric acid (50, 30and 30 mL) and the combined aqueous was basified to pH 7-9 with cooled saturated sodium bicarbonate solution. The yellow precipitation was filtered producing the crude products. After recrystallized in ethanol, the products were isolated as pure form in more than 85 % yields.

Reference： [1]Asian Journal of Chemistry,2014,vol. 26,p. 7269 - 7275

65
[ 104594-70-9 ]
[ 5538-51-2 ]
3-[3,4-bis[2-(acetyloxy)benzoyloxy]phenyl]-(2E)-2-propenoic acid 2-phenylethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 22℃; for 4h;Inert atmosphere;	Fig. 2 shows the synthesis of VP939. A solution of CAPE (500mg, 1.76mmol) and N,N-diisopropylethylamine (0.67ml, 3.87mmol) in 7ml of anhydrous tetrahydrofurane (THF) was added drop-wise to a solution of 2-(acetyloxy)benzoyl chloride (Sigma Aldrich, Italy; 769mg, 3.87mmol) in anhydrous THF (2ml) and the mixture was stirred under nitrogen for 4h at 22C. After removing the THF, the mixture was dissolved in ethyl acetate. The obtained organic phase was washed with water (2×75ml) followed by saturated sodium chloride solution, dried over sodium sulfate, filtered, and evaporated. The isolated crude material was purified by column chromatography (silica gel 60, 230-400mesh, Merck) using ethyl acetate/cyclohexane (3:7) as eluant. The title compound was obtained as a colorless sticky oil (861mg, 81%): IR (KBr) cm-1 3055, 2987, 1752, 1717, 1607, 1265, 1243, 1193, 1112, 1037, and 739; 1H NMR (DMSO-d6) delta 8.07-7.90 (m, 3H, aromatic), 7.83-7.64 (m, 3H+1H, aromatic+CH=CHCOO), 7.53-7.45 (m, 1H, aromatic), 7.42-7.18 (m, 9H, aromatic), 6.71 (d, J=16.0, 1H, CH=CHCOO), 4.38 (t, J=6.8Hz, 2H, OCH2CH2Ph), 2.98 (t, J=6.8Hz, 2H, OCH2CH2Ph), 2.21 (s, 3H, OCOCH3), 2.20 (s, 3H, OCOCH3). Anal. (C35H28O10) C, H.

Reference： [1]European Journal of Pharmacology,2015,vol. 752,p. 78 - 83

66
C₁₃H₂₆O₄ [ No CAS ]
[ 5538-51-2 ]
C₃₁H₃₈O₁₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With pyridine; dmap In dichloromethane at 20℃; for 24h; Inert atmosphere;
87%	With pyridine; dmap In dichloromethane at 20℃; Inert atmosphere;	Synthesis and Characterization of Oc-[G1]-(Asp)2 (6): Compound 4 (0.5 g, 0.00204 mol), DMAP (7.5 mg, 0.0006 mol), and pyridine (1.3 g, 0.016 mol, 0.98 g/mL) were dissolved in 50 mL of CH2Cl2. Compound 5 (1.6 g, 0.008 mol) was added drop-wise. The reaction mixture was stirred overnight at room temperature under N2 flow. The following day, 3 mL of nanopure water was added, followed by the addition of 40 mL of CH2Cl2. The solution was then washed three times with 50 mL of 1 M NaHCO3, three times with 50 mL of 10% NaHSO4, and three times with 50 mL of brine. The final solution was dried over MgSO4 to remove any remaining water. The solvent was then evaporated to yield an oil. The crude product was then purified using silica flash column chromatography (silica packed with hexanes) using ethylacetate:hexane (10:90) and then ethylacetate:hexane (15:85), and the product was isolated as a pale yellow oil. Yield: 947 mg, 87%. 1H NMR (CDCl3, 400 MHz): δ 7.92 [d, 2H], 7.56 [t, 2H], 7.28 [t, 2H], 7.11 [d, 2H], 4.49 [s, 3H], 4.13 [t, 2H], 2.32 [s, 5H], 1.58 [q, 1H], 1.37 [s, 2H], 1.18 [m, 10H], 0.85 [t, 3H] ppm. 13C NMR (CDCl3, 100 MHz): δ 1172.61, 69.62, 163.51, 151.01, 134.09, 131.45, 126.01, 123.90, 122.55, 66.15, 65.57, 46.60, 31.74, 29.11, 29.05, 28.5

Reference： [1]Kalathil, Akil A.; Kumar, Anil; Banik, Bhabatosh; Ruiter, Timothy A.; Pathak, Rakesh K.; Dhar, Shanta [Chemical Communications, 2016, vol. 52, # 1, p. 140 - 143]
[2]Current Patent Assignee: UNIVERSITY SYSTEM OF GEORGIA - US2017/87167, 2017, A1 Location in patent: Paragraph 0150; 0151; 0152

67
C₂₃H₄₂O₁₀ [ No CAS ]
[ 5538-51-2 ]
C₅₉H₆₆O₂₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With pyridine; dmap In dichloromethane at 20℃; for 24h; Inert atmosphere;
87%	With pyridine; dmap In dichloromethane at 20℃; Inert atmosphere;	Synthesis and Characterization of Oc-[G2]-(Asp)4 (9): Compound 8 (1 g, 0.002 mol), DMAP (153 mg, 0.0013 mol), and pyridine (2.7 g, 0.034 mol, 0.98 g/mL) were dissolved in 80 mL of CH2Cl2 and stirred at room temperature. Compound 5 (2.4 g, 0.011 mol) was then added drop-wise to the stirring solution. The reaction mixture was stirred overnight under N2 flow. The next day, 10 mL of CH2Cl2 was added. 10 min later, 3 mL ofnanopure water was added, and the resulting solution was washed three times with 50 mL of 1 M NaHCO3, three times with 50 mL of 10% NaHSO4 and three times with 50 mL of brine. The solution was then dried over MgSO4, and the solvent was evaporated to yield a dark brown oil. The crude product was then purified using silica flash column chromatography (silica packed with hexanes) using ethylacetate:hexane (5:95) followed by ethylacetate:hexane (10:90), ethylacetate:hexane (15:85), ethylacetate:hexane (20:80), ethylacetate:hexane (25:75) and finally ethylacetate:hexane (30:70). The separate fractions were concentrated and the purity of the concentrated product was checked by thin layer chromatography (TLC). The product showed two spots on TLC. This crude product was then purified using silica flash column (packed with CH2Cl2) initially with methanol:dichloromethane (0.5:99.5) and then methanol:dichloromethane (1:99). The solvent was evaporated to yield a pale yellow oil. Yield 1.2 g, 87%. 1H NMR (CDCl3, 400 MHz): δ 7.90 [d, 4H], 7.54 [t, 4H], 7.27 [t, 4H], 7.09 [d, 4H], 4.44 [m, 8H], 4.26 [m, 4H], 3.67 [t, 2H], 2.30 [s, 12H], 1.51 [q, 2H], 1.30 [s, 6H], 1.22 [m, 10H], 1.15 [m, 3H], 0.85 [t, 3H] ppm. 13C NMR (CDCl3, 400 MHz): δ 172.07, 171.82, 169.57, 163.40, 150.97, 134.13, 131.44, 126.06, 123.88, 122.46, 70.55, 65.79, 53.42, 46.66, 46.51, 31.74, 29.12, 28.41, 25.73, 22.60, 20.97, 17.84, 17.47, 14.08 ppm HRMS-ESI (m/z): [M+Na] calc. for C59H66NaO22 1149.3943. found 1149.3945.

Reference： [1]Kalathil, Akil A.; Kumar, Anil; Banik, Bhabatosh; Ruiter, Timothy A.; Pathak, Rakesh K.; Dhar, Shanta [Chemical Communications, 2016, vol. 52, # 1, p. 140 - 143]
[2]Current Patent Assignee: UNIVERSITY SYSTEM OF GEORGIA - US2017/87167, 2017, A1 Location in patent: Paragraph 0159; 0160

68
[ 5538-51-2 ]
[ 154-23-4 ]
(2R,3S)-3,3',4',5,7-penta-O-(2-O-acetylsalicyl)-2-(3',4'-dihydroxyphenyl)chroman-3,5,7-triol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.7%	With pyridine; In 1,4-dioxane; at 25℃; for 6h;	o-Acetylsalicyl chloride (1.9 g) and 0.9 g of pyridine were added onvigorous stirring to a solution of 0.5 g of catechol (I) in15 mL of dioxane. Next, the reaction mixture was vigorously stirred at 25C for 6 h and allowed to standovernight. After reaction completion, the resulting precipitate was separated by filtration, the filtrate wasconcentrated in a vacuum to a syrup, applied on achromatographic column filled with silica gel 60(Merck Millipore Corporation), and eluted with system A.Yield 1.53 g (80.7%). Tm = 91-93C. Rf = 0.70 (A).13C NMR (CDCl3, delta, ppm): 20.9 (C8''), 24.8 (C4),68.9 (C3), 77.3 (C2), 106.4 (C8), 108.1 (C6), 109.0(C4a), 116.4 (C6'), 117.7 (C5'), 121.6 (C2'), 123.8 (C1''),124.3 (C3''), 126.2 (C5''), 129.3 (C6"), 134.1 (C4"), 134.5(1'), 142.8 (C4'), 145.8 (C3'), 149.5 (C7), 150.2 (C5),150.5 (C2"), 161.7 (C8a), 168.7 (C7"), 169.6 (C9").For C60H44O21 anal. calcd. (%): C, 65.45; H, 4.00.Found (%): C, 65.48; H, 4.09.

Reference： [1]Doklady Chemistry,2016,vol. 468,p. 148 - 151
Dokl. Akad. Nauk,2016,vol. 468,p. 44 - 47,4

69
[ 29745-44-6 ]
[ 76918-64-4 ]
[ 5538-51-2 ]
ethyl 3-(2-hydroxybenzamido)-4-(picolinamido)benzoate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2016,vol. 138,p. 5483 - 5486

70
[ 24994-04-5 ]
[ 5538-51-2 ]
[ 112237-04-4 ]

Yield	Reaction Conditions	Operation in experiment
27.3%	Stage #1: 5-(p-tolyl)-1H-tetrazole; O-acetylsalicyloyl chloride With pyridine for 2h; Reflux; Inert atmosphere; Stage #2: With sodium hydroxide In ethanol; water for 1h; Reflux; Inert atmosphere;

Reference： [1]Deng, Ruiping; Li, Leijiao; Song, Mingxing; Zhao, Shuna; Zhou, Liang; Yao, Shuang [CrystEngComm, 2016, vol. 18, # 23, p. 4382 - 4387]

71
[ 24994-04-5 ]
[ 5538-51-2 ]
C₂₇H₂₁BN₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: pyridine / 2 h / Reflux; Inert atmosphere 1.2: 1 h / Reflux; Inert atmosphere 2.1: tetrahydrofuran / 8 h / Inert atmosphere; Reflux

Reference： [1]Deng, Ruiping; Li, Leijiao; Song, Mingxing; Zhao, Shuna; Zhou, Liang; Yao, Shuang [CrystEngComm, 2016, vol. 18, # 23, p. 4382 - 4387]

72
[ 5538-51-2 ]
[ 118-58-1 ]

Reference： [1]Molecules,2016,vol. 21

73
[ 1531595-91-1 ]
[ 5538-51-2 ]
2-(((trifluoromethyl)selanyl)carbonyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With iron In 1,4-dioxane at 20℃; for 1.5h; Inert atmosphere;	4.2. General procedure for trifluoromethylselenolation of acid chlorides 2 with [(bpy)Cu(SeCF₃)]₂ (1) General procedure: [(bpy)Cu(SeCF3)]2 (1) (166 mg, 0.225 mmol, 0.75 equiv), acid chlorides 2 (0.30 mmol, 1 equiv), Fe powder (1.7 mg, 0.030 mmol, 10 mol%), and dioxane (2.5 mL) were added to an oven dried 5 mL test tube with Teflon screw cap. The mixture was then stirred at r.t. for 1.5 h. Then the reaction mixture was filtered through a layer of Celite, eluted with diethyl ether. The resulting mixture was extracted by ethyl ether (10 mL x 3), and the combined organic layers was washed with water (10 mL x 3), and then dried over magnesium sulfate. The solvent was removed by rotary evaporation in ice bath and the resulting product was purified by column chromatography on silica gel with pentane/Et2O.

Reference： [1]Wang, Junwen; Zhang, Mengjia; Weng, Zhiqiang [Journal of Fluorine Chemistry, 2017, vol. 193, p. 24 - 32]

74
[ 108-01-0 ]
[ 64-19-7 ]
[ 5538-51-2 ]
2-(dimethylamino)ethyl acetylsalicylate acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: 2-(N,N-dimethylamino)ethanol; O-acetylsalicyloyl chloride With triethylamine In chloroform at 0 - 20℃; for 3h; Stage #2: acetic acid In chloroform	19.9 g (0.1 mol) of o-acetoxybenzoyl chloride was dissolved in 100 ml of chloroform. The mixture was cooled to 0 ° C. 15 ml of triethylamine and 8.9 g of dimethylaminoethanol were added to the reaction mixture. The mixture is stirred at room temperature for 3 hours. 6 g of acetic acid are added to the reaction mixture with stirring. The solid byproduct was removed by filtration and washed with chloroform (3 × 30 ml). The organic solution was evaporated. After drying, 29 g (93%) of the desired product was obtained. Hygroscopic product, solubility in water: 350 mg / ml, elementary analysis: C 15 H 21 NO 6, molecular weight: 311.33, calculated% C: 57.87, H: 6.80, N: 4.50, O: 30.83, measured% C: 57.82, H: 2.81 (s, 3 H), 2.90 (s, 6 H), 3.71 (m, 2 H), 4.69 (s, 3 H), 1 H-NMR (400 MHz, CDCL 3): delta: 2.09 (M, 2 H), 6.9 (b, 1 H), 7.18 (m, 1 H), 7.20 (m, 1 H), 7.47 (m, 1 H), 7.93 (m, 1 H).
93%	Stage #1: 2-(N,N-dimethylamino)ethanol; O-acetylsalicyloyl chloride With triethylamine In chloroform at 0 - 20℃; for 3h; Stage #2: acetic acid In chloroform	Preparation of dimethylaminoethylacetylsalicylate acetate O-acetoxybenzoyl chloride 19.9 g (0.1 mol) Was dissolved in 100 ml of chloroform. The mixture was cooled to 0 ° C. Triethylamine 15 ml And 8.9 g of dimethylaminoethanol were added to the reaction mixture. The mixture is stirred at room temperature for 3 hours. 6 g of acetic acid are added to the reaction mixture with stirring. The solid by-product was removed by filtration and washed with chloroform (3 × 30 ml). The organic solution was evaporated. After drying, 29 g (93%) of the desired product was obtained
93%	Stage #1: 2-(N,N-dimethylamino)ethanol; O-acetylsalicyloyl chloride With triethylamine In chloroform at 20℃; for 3h; Stage #2: acetic acid In chloroform at 20℃;	Preparation of dimethylaminoethylacetylsalicylate acetate 19.9 g (0.1 mol) of o-acetoxybenzoyl chloride was dissolved in 100 ml of chloroform. The mixture was cooled to 0 ° C. 15 ml of triethylamine and 8.9 g of dimethylaminoethanol were added to the reaction mixture. The mixture is stirred at room temperature for 3 hours. 6 g of acetic acid are added to the reaction mixture with stirring. The solid by-product was removed by filtration and washed with chloroform (3 × 30 ml). The organic solution was evaporated. After drying, 29 g (93%) of the desired product was obtained. Hygroscopic product, solubility in water: 350 mg / ml,

Reference： [1]Current Patent Assignee: TECHFIELDS BIOCHEM CO. LTD - JP2016/47841, 2016, A Location in patent: Paragraph 0024
[2]Current Patent Assignee: TECHFIELDS BIOCHEM CO. LTD - JP2017/119704, 2017, A Location in patent: Paragraph 0024
[3]Current Patent Assignee: TECHFIELDS BIOCHEM CO. LTD - JP2018/58899, 2018, A Location in patent: Paragraph 0024

75
[ 108-02-1 ]
[ 64-19-7 ]
[ 5538-51-2 ]
2-(2-(dimethylamino)ethyl)acetylthiosalicylate acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: captamine; O-acetylsalicyloyl chloride With triethylamine In chloroform at 0 - 20℃; for 3h; Stage #2: acetic acid In chloroform	19.9 g (0.1 mol) of o-acetoxybenzoyl chloride was dissolved in 100 ml of chloroform. The mixture was cooled to 0 ° C. 15 ml of triethylamine and 9.3 g of dimethylaminoethyl mercaptan were added to the reaction mixture. The mixture was stirred at room temperature for 3 h. 6 g of acetic acid was added to the reaction mixture with stirring. The solid byproduct was removed by filtration and washed with chloroform (3 × 30 ml). The organic solution was evaporated. After drying, 28 g (87%) of the desired product was obtained. Hygroscopic product, Calculation% C: 55.03, H: 6.47, N: 4.28, O: 24.43, S: 9.79, measured% C: Solubility in water: 320 mg / ml, elemental analysis: C15 H21 NO5 S, molecular weight: 327.4, 1 H-NMR (400 MHz, CDCL 3): delta: 2.09 (s, 3 H), 2.21 (s, 3 H), 2.90 (s, 6 H), 1 H-NMR (55 Hz, (M, IH), 7.55 (m, IH), 7.94 (m, IH), 3.91 (m, 2H), 6.9 (b, IH), 7.26 (m, IH), 7.58 (m, IH)
87%	Stage #1: captamine; O-acetylsalicyloyl chloride With triethylamine In chloroform at 0 - 20℃; for 3h; Stage #2: acetic acid In chloroform	19.9 g (0.1 mol) of o-acetoxybenzoyl chloride, Was dissolved in 100 ml of chloroform. The mixture was cooled to 0 ° C. Triethylamine 15 ml And 9.3 g of dimethylaminoethyl mercaptan were added to the reaction mixture. The mixture was stirred at room temperature for 3 h. 6 g of acetic acid was added to the reaction mixture with stirring. The solid by-product was removed by filtration, And washed with chloroform (3 × 30 ml). The organic solution was evaporated. After drying, 28 g (87%) of the desired product was obtained.
87%	Stage #1: captamine; O-acetylsalicyloyl chloride With triethylamine In chloroform at 20℃; for 3h; Stage #2: acetic acid In chloroform at 20℃;	Preparation of S-dimethylaminoethylacetylthiosalicylate acetate 19.9 g (0.1 mol) of o-acetoxybenzoyl chloride was dissolved in 100 ml of chloroform.The mixture was cooled to 0 ° C.15 ml of triethylamine and 9.3 g of dimethylaminoethyl mercaptan were added to the reaction mixture.The mixture was stirred at room temperature for 3 h. 6 g of acetic acid was added to the reaction mixture with stirring.The solid by-product was removed by filtration,And washed with chloroform (3 × 30 ml).The organic solution was evaporated.After drying,28 g (87%) of the desired product was obtained

Reference： [1]Current Patent Assignee: TECHFIELDS BIOCHEM CO. LTD - JP2016/47841, 2016, A Location in patent: Paragraph 0025
[2]Current Patent Assignee: TECHFIELDS BIOCHEM CO. LTD - JP2017/119704, 2017, A Location in patent: Paragraph 0025
[3]Current Patent Assignee: TECHFIELDS BIOCHEM CO. LTD - JP2018/58899, 2018, A Location in patent: Paragraph 0025

76
[ 64-19-7 ]
[ 108-00-9 ]
[ 5538-51-2 ]
2-(2-(dimethylamino)ethyl)acetylsalicylamide acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90.2%	Stage #1: N,N-dimethylethylenediamine; O-acetylsalicyloyl chloride With triethylamine In chloroform at 0 - 20℃; Stage #2: acetic acid In chloroform	19.9 g (0.1 mol) of o-acetoxybenzoyl chloride was dissolved in 100 ml of chloroform. The mixture was cooled to 0 ° C. 15 ml of triethylamine and 8.9 g of dimethylaminoethylamine were added to the reaction mixture. The mixture was stirred at room temperature for 3 h. 6 g of acetic acid was added to the reaction mixture with stirring. The solid byproduct was removed by filtration and washed with chloroform (3 × 30 ml). The organic solution was evaporated. After drying, 28 g (90.2%) of the desired product was obtained. Hygroscopic product, solubility in water: 350 mg / ml, Calculation% C: 58.05, H: 7.15, N: 9.03, O: 25.78, measured% C: 58.02, H: hygroscopic product, water solubility: 350 mg / ml, elemental analysis: C 15 H 22 N 2 O 5, 3.2), 2.21 (s, 3 H), 2.90 (s, 6 H), 3.54 (m, 2 H), 3.64 (m, 2 H), 1 H-NMR (400 MHz, CDCL 3): delta: 2.09(s,3H)2.21(s,3H)2.90(s,6H)3.54(m,2H)3.64(t,2H)6.9(b,1H)7.8(b,1H)7.25(m,1H)7.26(m,1H) 7.48(m,1H)7.92(m,1H)
90.2%	Stage #1: N,N-dimethylethylenediamine; O-acetylsalicyloyl chloride With triethylamine In chloroform at 0 - 20℃; for 3h; Stage #2: acetic acid In chloroform	Preparation of N-dimethylaminoethyl acetylsalicylamide acetic acid 19.9 g (0.1 mol) of o-acetoxybenzoyl chloride, Was dissolved in 100 ml of chloroform. The mixture was cooled to 0 ° C. Triethylamine 15 ml And 8.9 g of dimethylaminoethylamine Was added to the reaction mixture. The mixture was stirred at room temperature for 3 h. 6 g of acetic acid was added to the reaction mixture with stirring. The solid by-product was removed by filtration, And washed with chloroform (3 × 30 ml). The organic solution was evaporated. After drying, 28 g (90.2%) of the desired product was obtained
28 g	Stage #1: N,N-dimethylethylenediamine; O-acetylsalicyloyl chloride With triethylamine In chloroform at 20℃; for 3h; Stage #2: acetic acid In chloroform at 20℃;	Preparation of N-dimethylaminoethylacetylsalicylamide acetic acid 19.9 g (0.1 mol) of o-acetoxybenzoyl chloride was dissolved in 100 ml of chloroform. The mixture was cooled to 0 ° C. 15 ml of triethylamine and 8.9 g of dimethylaminoethylamine were added to the reaction mixture. The mixture was stirred at room temperature for 3 h. 6 g of acetic acid was added to the reaction mixture with stirring. The solid by-product was removed by filtration and washed with chloroform (3 × 30 ml). The organic solution was evaporated. After drying, 28 g (902%) of the desired product was obtained

Reference： [1]Current Patent Assignee: TECHFIELDS BIOCHEM CO. LTD - JP2016/47841, 2016, A Location in patent: Paragraph 0026
[2]Current Patent Assignee: TECHFIELDS BIOCHEM CO. LTD - JP2017/119704, 2017, A Location in patent: Paragraph 0026
[3]Current Patent Assignee: TECHFIELDS BIOCHEM CO. LTD - JP2018/58899, 2018, A Location in patent: Paragraph 0026

77
[ 436-77-1 ]
[ 5538-51-2 ]
7-O-(2-acetoxylbenzoyl)-fangchinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%		General procedure: Fangchinoline (100 mg, 0.16 mmol) was dissolved in 8 mL of CH2Cl2. The mixture was cooled to 0 C under N2. Pyridine (25 mg, 0.32 mmol) was added to the mixture. The solution was stirred for 1 h and various types of acyl chlorides (0.24 mmol, in 2 mL of CH2Cl2) were added dropwise over 10 min. The mixture was stirred for 1 h at 0 C and was stirred another hour at room temperature. The mixture was washed with water, dried over anhydrous Na2SO4 and filtered. After being concentrated under vacuum, the residue was purified by flash chromatography on silica gel using CH2Cl2/CH3OH as eluant to afford the desired products 6a-6p.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 533 - 536

78
[ 3425-46-5 ]
[ 98-32-8 ]
[ 5538-51-2 ]
2-(((2-hydroxy-5-sulfamoylphenyl)carbamoselenoyl)carbamoyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%		General procedure: Potassium selenocyanate (0.14 g, 1.0 mmol) dissolved inacetone (5.0 mL) was treated with the appropriate acyl chloride1a?i (1.0 mmol). The reaction mixture was stirred at r.t. for15 min, followed by addition of appropriate aminobenzensulfonamide(2?6) (1.0 mmol) and stirred for 40 min at the same temperature.After this time the mixture was quenched with H2O and theformed precipitate was filtered-off and dried on air. The obtainedproducts 7?22 were used as they are.

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 3567 - 3573

79
[ 5538-51-2 ]
[ 36791-04-5 ]
C₁₇H₁₈N₄O₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81.3%	With potassium hydrogencarbonate; In tetrahydrofuran; at 60℃; for 2h;	24.4 g of <strong>[36791-04-5]ribavirin</strong> was dissolved in 500 ml of tetrahydrofuran, 19 g of potassium bicarbonate and 21.1 g of o-acetylbenzoyl chloride were added, heated to 60 C. for 2 hours, cooled to room temperature, washed with water, and the organic phase was dried over anhydrous magnesium sulfate overnight. The solvent was removed under pressure, column chromatography and ethyl acetate-methanol were used as eluents. The corresponding fractions were collected, the solvent was removed under reduced pressure, and the residue was dried to obtain 33.0 g of a solid with a yield of 81.3%.

Reference： [1]Patent: CN107513055,2017,A .Location in patent: Paragraph 0025-0031

80
[ 446292-10-0 ]
[ 5538-51-2 ]
C₂₃H₂₃N₃O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃;	Under anhydrous and anaerobic conditions,(S)-2-((2-Oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-ylmethyl)isoindole -The 1,3-diketone (V, 1 mmol) was dissolved in dichloromethane and N,N-diisopropylethylamine (2.0 eq) was added.2-Acetoxy-benzoyl chloride (IV, 1.5 eq) was reacted overnight at room temperature.The reaction was monitored by TLC, and the reaction was completed, washed twice with water, extracted with dichloromethane, and purified by column chromatography.The compound of formula (I) was obtained in a yield of 73% as calculated by (V).

Reference： [1]Patent: CN107827882,2018,A .Location in patent: Paragraph 0027; 0028; 0029

81
[ 33332-29-5 ]
[ 5538-51-2 ]
2-((5-chloropyrazin-2-yl)carbamoyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%		General procedure: Method B is a modification of Method A and was performed under nitrogen atmosphere andwith extended work-up. Substituted benzoyl chloride (1.5 mmol, 1.2 equiv) was placed into the askunder nitrogen, diluted with dry DCM (5 mL) and dry pyridine (400 mg, 5 mmol, 4 equiv) was added.The mixture was mixed for 5 min under nitrogen. Then, <strong>[33332-29-5]5-chloropyrazin-2-amine</strong> (162 mg, 1.25 mmol,1 equiv) dissolved in DCM (10 mL) was added dropwise over 10 min under nitrogen ow. The askwas closed by septum and stirred for additional 6 h. After reaction, the mixture was diluted with DCMto the final volume of 40 mL and washed with water (1 30 mL), 5% (m/m) aqueous NaHCO3 solution(1 30 mL), and brine (1 30 mL). The organic layer was dried over anhydrous Na2SO4 and adsorbedon silica (4 g) by evaporating the solvents under reduced pressure. Automated flash chromatographywas run using same conditions as described in Method A. If needed, the products were recrystallizedfrom hot EtOH (crystallization initiated by cooling and dropwise addition of cold water).

Reference： [1]Molecules,2018,vol. 23

82
[ 69-72-7 ]
[ 5538-51-2 ]
[ 552-94-3 ]

Reference： [1]Patent: DE220941,
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 9,p. 928

83
[ 5538-51-2 ]
[ 32865-61-5 ]

Yield	Reaction Conditions	Operation in experiment
78%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In o-xylene at 150℃; for 12h;

Reference： [1]Lee, Yong Ho; Morandi, Bill [Nature Chemistry, 2018, vol. 10, # 10, p. 1016 - 1022]

84
[ 13500-53-3 ]
[ 5538-51-2 ]
[ 852055-92-6 ]

Reference： [1]Patent: WO2005/46575,2005,A2

85
[ 98-96-4 ]
[ 5538-51-2 ]
C₁₄H₁₁N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.4832 g		1) Weigh 1.0g of acetylsalicylic acid,Add it together with 10 mL of dichloromethaneInto a 100mL single-mouth bottle,Stir at room temperature for 30 min.After the acetylsalicylic acid is fully dissolved,Add 5 ml of thionyl chloride and stir at room temperature for 30 min.Then add 1 drop of DMF,After stirring, it is found that gas is slowly generated.The temperature was raised to 40 C and refluxed for 3 hours.Finally, distillation under reduced pressure gave crude acetylsalicylic acid chloride.2) 0.6g <strong>[98-96-4]pyrazinamide</strong> and 40mLChloroform is placed in a three-neck bottle.Warm up to 40 C to fully dissolve it,Add 1 mL of triethylamine,A <strong>[98-96-4]pyrazinamide</strong> reaction solution was obtained.3) Add the crude acetyl salicyl chloride obtained in step 1Dilute in 2 ml of dichloromethane,A reaction solution of acetylsalicylic acid chloride was obtained.Then slowly add the acetylsalicylic acid chloride reaction solution to step 2In the <strong>[98-96-4]pyrazinamide</strong> reaction solution,The dropping process is completed within 10 minutes.The temperature was then raised to 35-45 C to reflux the reaction.acetylsalicylic acid 4) After 1 hour, the sampling board is monitored.Found that new substances are produced,After the reaction for 12 hours, some of the starting <strong>[98-96-4]pyrazinamide</strong> remained unreacted.Stop the reaction.5) Take out the reaction solution for post-treatment,Purification by column chromatography gave 0.4832 g of the acetylsalicylic acid-pyrazine amide hybrid product.The purity of the product was determined by HPLC to be 95.4%.The calculated yield was 35%.

Reference： [1]Patent: CN109053602,2018,A .Location in patent: Paragraph 0030; 0033-0036; 0039-0048; 0051-0054; 0057-0060

86
[ 100-37-8 ]
[ 5538-51-2 ]
2C₁₅H₂₁NO₄*H₂O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78.01%		Acetyl salicyl chloride (19.86 g, 0.1 mol, 1.0 eq) was placed in a 250 ml three-necked flask, and 100 mL of dichloromethane was added thereto to stir and dissolve. The mixture was cooled to 1-2 C in an ice water bath, and diethylamino ethanol (12.89 g, 0.11 mol, 1.1 eq), was added A small amount of white smoke was formed by the addition of triethylamine (15.18 g, 0.15 mol, 1.5 eq).Slowly rise to room temperature, After stirring for 4 hours at room temperature, stop the reaction. Add 60 mL of saturated sodium carbonate solution to the system. Adjust the pH to 9-10;Liquid separation,The organic phase is washed with 60 mL of a saturated saline solution.The organic layer was dried over anhydrous sodium sulfate, and the solid was filtered, and the solvent was evaporated. The liquid was dissolved in 60 mL of n-hexane, and concentrated sulfuric acid (4.35 g, 0.5 eq) was added under cooling in an ice water bath to precipitate a white solid. The crude product was recrystallized from 100 ml of dichloromethane.25.6 g of a white solid were obtained in a yield of 78.01%.

Reference： [1]Patent: CN104276962,2019,B .Location in patent: Paragraph 0052-0054

87
[ 2518-24-3 ]
[ 5538-51-2 ]
2-((1,3-dioxoisoindolin-4-yl)carbamoyl)phenyl acetate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019

88
[ 82-45-1 ]
[ 5538-51-2 ]
C₂₃H₁₅NO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With triethylamine In dichloromethane at 0 - 60℃; for 15.5h;	2.1.2. Synthesis of Asp-X3 The synthesis scheme for Asp-X3 is shown in Fig. 1. First, 6.51 g 1-amino-anthraquinone and 6 ml triethylamine were dispersed in 20 mlCH2Cl2 inside a 100-ml three-neck flask, and the reaction mixture wascooled to 0 °C in an ice bath followed by the dropwise addition of acetylsalicylrylchloride (obtained above) over a 15-min interval whilestirring. After that, the mixture was continuously stirred for another 30min, and then incubated at 60 °C for 15 h while stirring. Next, the reactionwas allowed to cool to 40 °C and then filtered through a Buchnerfunnel, and the filtrate was collected, and the excess solvent wasremoved by rotary evaporation. The residue was dissolved in 5 mlCH2Cl2 and washed three times with 5% NaHCO3 saturated aqueoussolution in a separating funnel. The bottom (organic) phase wascollected and anhydrous MgSO4 was added to absorb the extra waterand then removed by filtration. CH2Cl2 in the filtrate was removed byrotary evaporation. The residue was redissolved in 5 ml CH2Cl2 andsubjected to column chromatography (silica gel, CH2Cl2/MeOH = 200:1to 40:1), followed by recrystallization in Methylene Chloride-PetroleumEther.

Reference： [1]Lin, Shan; Zhang, Yue; Wang, Zeyu; Zhang, Shuang; Li, Yingjie; Fan, Yuhua; Li, Dan; Li, Sen; Bai, Yuhua [European Journal of Pharmacology, 2021, vol. 900]

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Ghs Precautionary Statements

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
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P243	Take precautionary measures against static discharge.
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P260	Do not breathe dust/fume/gas/mist/vapours/spray.
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P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
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P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Ghs Hazard Statements

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere