[ CAS No. 2491-38-5 ] {[proInfo.proName]}

Name: 2491-38-5|2-Bromo-1-(4-hydroxyphenyl)ethanone|98%
Brand: Ambeed
SKU: A172579
Price: 5.0 USD
Availability: InStock
Rating: 98 (25 reviews)

,{[proInfo.pro_purity]}

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

HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

DV 2D 3D

3d Animation Molecule Structure of 2491-38-5

Structure of 2491-38-5 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 2491-38-5 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 2491-38-5 ]

SDS Specification

Alternatived Products of [ 2491-38-5 ]

Product Details of [ 2491-38-5 ]

CAS No. :	2491-38-5	MDL No. :	MFCD00072424
Formula :	C₈H₇BrO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	LJYOFQHKEWTQRH-UHFFFAOYSA-N
M.W :	215.04	Pubchem ID :	4964
Synonyms :	PTP Inhibitor I;4-Hydroxyphenacyl bromide;Protein Tyrosine Phosphatase Inhibitor I;SHP-1 Inhibitor II;α-Bromo-4-hydroxyacetophenone	Chemical Name :	2-Bromo-1-(4-hydroxyphenyl)ethanone

Calculated chemistry of [ 2491-38-5 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	46.53
TPSA :	37.3 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) :	-6.31 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.39
Log Po/w (XLOGP3) :	1.83
Log Po/w (WLOGP) :	1.97
Log Po/w (MLOGP) :	1.59
Log Po/w (SILICOS-IT) :	2.21
Consensus Log Po/w :	1.8

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.6
Solubility :	0.543 mg/ml ; 0.00252 mol/l
Class :	Soluble
Log S (Ali) :	-2.23
Solubility :	1.26 mg/ml ; 0.00584 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.04
Solubility :	0.198 mg/ml ; 0.000923 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.4

Safety of [ 2491-38-5 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P501-P260-P270-P234-P264-P280-P390-P303+P361+P353-P301+P330+P331-P363-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P406-P405	UN#:	3261
Hazard Statements:	H302-H314-H290	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 2491-38-5 ]

* 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 [ 2491-38-5 ]
Downstream synthetic route of [ 2491-38-5 ]

[ 2491-38-5 ] Synthesis Path-Upstream 1~9

1
[ 100-66-3 ]
[ 598-21-0 ]
[ 2491-38-5 ]
[ 2491-36-3 ]

Reference： [1] Patent: US2838570, 1955, ,
[2] Patent: US2838570, 1955, ,
[3] Patent: US2838570, 1955, ,

2
[ 99-93-4 ]
[ 2491-38-5 ]
[ 1836-06-2 ]

Reference： [1] Bulletin of the Chemical Society of Japan, 1992, vol. 65, # 1, p. 295 - 297

3
[ 2491-38-5 ]
[ 100-39-0 ]
[ 4254-67-5 ]

Yield	Reaction Conditions	Operation in experiment
43%	With silver carbonate In tetrahydrofuran at 0 - 20℃; for 16 h;	Step 1: Preparation of l-(4-(benzyloxy)phenyl)-2-bromoethanone [00170] To a solution of 2-bromo- 1 -(4-hydroxyphenyl)ethanone (2 g, 9.3 mmol) in tetrahydrofuran (70 mL) was added silver carbonate (5.128 g, 18.6 mmol) and the reaction mixture was cooled to 0 °C. Benzyl bromide (1.32 m L, 11.16 mmol) was added drop wise and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was filtered through celite, the filtrate was diluted with ethyl acetate (200 mL) and washed with water (60 mL x 2). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude was purified by column chromatography using 6percent ethyl acetate in hexane to afford title l-(4-(benzyloxy)phenyl)-2-bromoethanone (1.22 g, 43percent yield) as a white solid. Calculated M+H: 306.17; Found M+H: 306.

Reference： [1] Patent: WO2016/49165, 2016, A1, . Location in patent: Paragraph 00170

4
[ 2491-38-5 ]
[ 4254-67-5 ]

Reference： [1] Journal of Organic Chemistry, 2015, vol. 80, # 19, p. 9713 - 9721
[2] Journal of Organic Chemistry, 2015, vol. 80, # 19, p. 9713 - 9721

5
[ 2491-38-5 ]
[ 17194-82-0 ]

Reference： [1] Synthetic Communications, 1997, vol. 27, # 7, p. 1133 - 1141

6
[ 2491-38-5 ]
[ 124-41-4 ]
[ 32136-81-5 ]

Reference： [1] Journal of Medicinal Chemistry, 1988, vol. 31, # 1, p. 55 - 59
[2] Chemical Communications, 2015, vol. 51, # 34, p. 7349 - 7351
[3] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 1, p. 191 - 194
[4] Patent: WO2004/52816, 2004, A1, . Location in patent: Page 38
[5] Patent: WO2004/113273, 2004, A1, . Location in patent: Page 37

7
[ 2491-38-5 ]
[ 32136-81-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium hydroxide In methanol	EXAMPLE 3 Preparation of alpha-methoxy-4-hydroxyacetophenone 2 g of alpha-bromo-4-hydroxyacetophenone are dissolved in 11 g of methanol. 30 g of a saturated solution of sodium hydroxide in methanol (1 g NaOH/ 4.2 ml methanol) is added dropwise to the alpha-bromo-4-hydroxyacetophenone solution. After the addition is complete, the solution is added to 30 g of ice and acidified to pH 6. Alpha-methoxy-4-hydroxyacetophenone precipitates out and is filtered and dried to a greenish yellow product in about 85percent yield; the product is determined by 1-H-NMR to be substantially pure.

Reference： [1] Patent: US5107034, 1992, A,

8
[ 2491-38-5 ]
[ 7440-44-0 ]
[ 32136-81-5 ]

Reference： [1] Patent: US5107034, 1992, A,

9
[ 2491-38-5 ]
[ 19745-72-3 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 5, p. 2550 - 2557
[2] Chemical and Pharmaceutical Bulletin, 2015, vol. 63, # 8, p. 628 - 635

[ 2491-38-5 ] Synthesis Path-Downstream 1~88

1
[ 2491-38-5 ]
[ 75-16-1 ]
[ 770-39-8 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1985,p. 1373 - 1380

2
[ 2491-38-5 ]
[ 75-16-1 ]
[ 770-39-8 ]
[ 98815-43-1 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1985,p. 1373 - 1380

3
[ 2491-38-5 ]
[ 75-16-1 ]
[ 770-39-8 ]
[ 98815-43-1 ]
4-(2-Bromo-1-hydroxy-1-methyl-ethyl)-phenol [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1985,p. 1373 - 1380

4
[ 2491-38-5 ]
[ 124-41-4 ]
[ 32136-81-5 ]

Yield	Reaction Conditions	Operation in experiment
		P10.1 1.8 g of 2-BROMO-1- (4-HYDROXY-PHENYL)-ETHANONE in 10 ml of methanol are added dropwise to 16 ml of 5.4M sodium methoxide in methanol and 50 ml of methanol, and stirring is carried out for 30 minutes at 60C. The reaction mixture is concentrated and the residue is taken up in water and adjusted to pH 1 with concentrated hydrochloric acid. Extraction with ethyl acetate is then carried out, the organic phase is concentrated and the crude product is purified over silica gel. 1- (4-HYDROXY-PHENYL)-2-METHOXY-ETHANONE is OBTAINED.'H-NMR (CDCI3) 300MHZ : 3.50 (s, 3H), 4.68 (s, 2H), 6.23 (s, 1 H), 6.91 (d, 2H), 7.90 (d, 2H).
	In methanol; at 60.0℃; for 0.916667h;	3.0 g OF 2-BROMO-1- (4-HYDROXY-PHENYL)-ETHANONE in 25 ML of methanol are added dropwise in the course of 10 minutes to a solution of 7.5 g of sodium METHANOLATE in 80 ml of methanol. Stirring is then carried out at 60C for 45 minutes. The reaction mixture is cooled, poured into dilute hydrochloric acid and extracted with ethyl acetate. After concentration of the organic phases and crystallisation from diethyl ether, 1- (4-HYDROXY-PHENYL)-2-METHOXY- ethanone is OBTAINED. 1H-NMR (CDCI3) 300MHZ : 3.50 (s, 3H), 4.70 (s, 2H), 6.62 (s, 1H), 6.91 (d, 2H), 7.89 (d, 2H)

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 55 - 59
[2]Chemical Communications,2015,vol. 51,p. 7349 - 7351
[3]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 191 - 194
[4]Patent: WO2004/52816,2004,A1 .Location in patent: Page 38
[5]Patent: WO2004/113273,2004,A1 .Location in patent: Page 37

5
[ 2491-38-5 ]
[ 99-93-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With diethyl ether In lithium hydroxide monohydrate at 20℃; for 3h; Schlenk technique; Irradiation;	3. General procedure for the reaction of reductive dehalogenation General procedure: To a 10 mL schlenk tube, 1 (0.2 mmol), H2O (1.6 mmol) and Et2O (4 mL) were added in sequence. The reaction mixture was stirred and irradiated by 40 W Kessil purple LED (390 nm) at room temperature . After the reaction was completed, the reaction mixture was purified by flash column chromatography using PE/EtOAc as the eluent to give the desired product.
93%	With DMBI In tetrahydrofuran for 3h; Heating;
85%	With sodium hydrogen telluride In ethyl acetate for 1h; Ambient temperature;

	Multi-step reaction with 3 steps 1.1: potassium carbonate / methanol / 20 °C 1.2: 1 h 2.1: hydrogenchloride / methanol; lithium hydroxide monohydrate; isopropanol / 4 h 3.1: aq. phosphate buffer / pH 5.6 / Irradiation
	Multi-step reaction with 2 steps 1: N,N,N-tributyl-1-butanaminium iodide; potassium carbonate / dichloromethane; lithium hydroxide monohydrate / 20 °C 2: bis[(2,2,2-trifluoroacetyl)oxy]palladium; 5,5'-bis[di(3,5-di-t-butyl-4-methoxyphenyl)phosphino]-4,4'-bi-1,3-benzodioxole; hydrogen / propan-2-one / 24 h / 20 °C / 22502.3 Torr / Glovebox; Autoclave

Reference： [1]Chen, Jiajia; Chen, Jianhui; Luo, Yanshu; Xia, Yuanzhi; Zhang, Jinrong [Tetrahedron Letters, 2022]
[2]Chikashita, Hidenori; Ide, Hisao; Itoh, Kazuyoshi [Journal of Organic Chemistry, 1986, vol. 51, # 26, p. 5400 - 5405]
[3]Osuka, Atsuhiro; Suzuki, Hitomi [Chemistry Letters, 1983, p. 119 - 120]
[4]Bownik, Iwona; Šebej, Peter; Literák, Jaromír; Heger, Dominik; Šimek, Zdeněk; Givens, Richard S.; Klán, Petr [Journal of Organic Chemistry, 2015, vol. 80, # 19, p. 9713 - 9721]
[5]Chen, Jianzhong; Zhang, Zhenfeng; Liu, Delong; Zhang, Wanbin [Angewandte Chemie - International Edition, 2016, vol. 55, # 29, p. 8444 - 8447][Angew. Chem., 2016, vol. 128, # 29, p. 8584 - 8587]

6
[ 99-93-4 ]
[ 2491-38-5 ]
[ 1836-06-2 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1992,vol. 65,p. 295 - 297

7
[ 13031-43-1 ]
[ 2491-38-5 ]

Reference： [1]Russian Journal of Organic Chemistry,1994,vol. 30,p. 881 - 887
Zhurnal Organicheskoi Khimii,1994,vol. 30,p. 827 - 832
[2]Nippon Kagaku Zasshi,1959,vol. 80,p. 212
Chem.Abstr.,1961,p. 4406
[3]Letters in Organic Chemistry,2016,vol. 13,p. 672 - 677

8
[ 2491-38-5 ]
[ 27317-69-7 ]
[ 270090-90-9 ]

Reference： [1]Journal of the American Chemical Society,2000,vol. 122,p. 2687 - 2697
[2]Journal of the American Chemical Society,1997,vol. 119,p. 8369 - 8370

9
[ 2491-38-5 ]
[ 5052-95-9 ]
[ 184716-27-6 ]

Yield	Reaction Conditions	Operation in experiment
	In butanone;	EXAMPLE 5 (R,S)-8-{2-hydroxy-2-[4-(quinol-2-ylmethoxy)phenyl]ethyl}-<strong>[5052-95-9]3,8-diaza-1-oxa-2-oxospiro[4,5]decane</strong> STR39 Step A 43.5 g (0.2 mol) of 4-bromoacetylphenol, 62.4 g (0.4 mol) of <strong>[5052-95-9]3,8-diaza-1-oxa-2-oxospiro[4,5]decane</strong> and 1500 ml of methyl ethyl ketone are introduced into a flask. The mixture is heated at reflux for 14 hours. The mixture is cooled and the crystals are suction-filtered and washed with a 10% sodium carbonate solution and then with water. Drying is carried out at 50 C. under 67 Pa. There are obtained 34.8 g of 8-{2-(4-hydroxyphenyl)-2-oxoethyl}-<strong>[5052-95-9]3,8-diaza-1-oxa-2-oxospiro[4,5]decane</strong>, m.p.(cap): 250 C.

Reference： [1]Patent: US5698567,1997,A

10
[ 2491-38-5 ]
[ 169315-44-0 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium azide In methanol; water at 0 - 20℃;	General procedure for α-azidoacetophenone synthesis General procedure: To a stirred solution of NaN3 (0.29 g, 4.4 mmol) in H2O (4 mL) was added α-bromoacetophenone (4.0 mmol) in MeOH (8 mL) dropwise at 0 C. The reaction mixture was warmed to room temperature and stirred for 2.5-3.5 h. After completion of the reaction, MeOH was removed under reduced pressure. The crude residue diluted with H2O (10 mL) and extracted with EtOAc (2 x 40 mL). The combined organic layer was washed with H2O (2 x 15 mL) and brine (15 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The crude was purified by column chromatography (EtOAc/hexane=1/5-1/3) to afford the pure α-azidoacetophenone as white solid.
92%	With sodium azide In water; acetone at 20℃;
47%	With sodium azide In N,N-dimethyl-formamide at 20℃; for 2h;

	With sodium azide; Aliquat 336 In toluene at 55℃;
	With sodium azide In ethanol; water at 20℃;
	With sodium azide
	With sodium azide In water; acetone for 24h;
	With sodium azide In acetone at 40℃; for 2h;	1 The resulting α-bromo-4-hydroxyacetophenone (1.075 g, 5.0 mmol) was dissolved in acetone (20 mL), Sodium azide (0.39 g, 6.0 mmol) was then added to the solution. Stir for 2 hours at 40°C. After cooling to room temperature, Pour 50 mL of water into the solution. Extract with ethyl acetate (3 x 50 mL) Liquid separation, The organic phase is dried over anhydrous sodium sulfate. Suction filtration The residue obtained after removal of the solvent under reduced pressure was separated by column chromatography (eluent: ethyl acetate/petroleum ether = 1:15, v/v). Alpha-azido-4-hydroxyacetophenone is obtained.
	With sodium azide In acetone at 20℃;	General Procedure for 2-Azido-Ketone Synthesis of phenacyl azides (2)2: General procedure: NaN3 (2.0 mmol) was added to a solution of the α-bromo-ketone (1.0 mmol) in acetone15 mL at room temperature. The reaction was stirred for 1-3 h. After addition of water theproduct was extracted with EtOAc, dried over NaSO4 and concentrated in vacuo. The crudeproduct was purified by column chromatography on silica gel (100-200 mesh) using an ethylacetate/hexane (9:1) to yield desired phenacyl azide.

Reference： [1]Damodar, Kongara; Shin, Sooyong; Jeon, Sung Ho; Lee, Jeong Tae [Tetrahedron Letters, 2021, vol. 85]
[2]Madea; Slanina; Klán [Chemical Communications, 2016, vol. 52, # 87, p. 12901 - 12904]
[3]Edegger, Klaus; Gruber, Christian C.; Poessl, Tina M.; Wallner, Sabine R.; Lavandera, Ivan; Faber, Kurt; Niehaus, Frank; Eck, Juergen; Oehrlein, Reinhold; Hafner, Andreas; Kroutil, Wolfgang [Chemical Communications, 2006, # 22, p. 2402 - 2404]
[4]Widler, Leo; Green, Jonathan; Missbach, Martin; Susa, Mira; Altmann, Eva [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 6, p. 849 - 852]
[5]Cuetos, Aníbal; Bisogno, Fabricio R.; Lavandera, Iván; Gotor, Vicente [Chemical Communications, 2013, vol. 49, # 26, p. 2625 - 2627]
[6]Lu, Xiao-Feng; Yang, Zheng; Huang, Nian-Yu; He, Hai-Bo; Deng, Wei-Qiao; Zou, Kun [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 17, p. 3726 - 3729]
[7]Salahi, Farbod; Purohit, Vatsal; Ferraudi, Guillermo; Stauffacher, Cynthia; Wiest, Olaf; Helquist, Paul [Organic Letters, 2018, vol. 20, # 9, p. 2547 - 2550]
[8]Current Patent Assignee: CHINA THREE GORGES UNIVERSITY - CN104788436, 2018, B Location in patent: Paragraph 0079; 0083
[9]Gour, Jitendra; Gatadi, Srikanth; Pooladanda, Venkatesh; Ghouse, Shaik Mahammad; Malasala, Satyaveni; Madhavi; Godugu, Chandraiah; Nanduri, Srinivas [Bioorganic Chemistry, 2019, vol. 93]

11
[ 2491-38-5 ]
[ 5029-61-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With nitric acid In methanol at 0 - 20℃; for 3h; Large scale;	S1 S1: 2.13kg of raw material 2-bromo-4'-hydroxyacetophenone (1 equivalent), its structural formula is:Dissolve in 10L (5 volumes) methanol, and cool the resulting solution A to 0 ° C,And add 0.63kg of nitric acid dropwise to solution A,After the dropwise addition is completed, the resulting reaction system is reacted at room temperature for 3 hours,After the reaction is completed, the material is discharged under ice water conditions.Centrifuge the product obtained from the discharge, use the centrifugal force generated by the centrifuge to separate the liquid and solid particles in the product obtained from the discharge, and dry the solid particles2.59 kg of intermediate I was obtained. Intermediate I was a nitro compound with the structural formula:In this step, intermediate I is obtained by dissolving 2-bromo-4'-hydroxyacetophenone as a raw material in concentrated sulfuric acid and adding nitric acid, and the reaction yield is 100%.
93%	With trifluoromethylsulfonic anhydride; tetramethylammonium nitrate In dichloromethane for 27h;

Reference： [1]Current Patent Assignee: SUZHOU KAIRUI MEDICINE SCIENCE TECH - CN111018902, 2020, A Location in patent: Paragraph 0014
[2]Shackelford, Scott A.; Anderson, Mark B.; Christie, Lance C.; Goetzen, Thomas; Guzman, Mark C.; Hananel, Martha A.; Kornreich, Wayne D.; Li, Haitao; Pathak, Ved P.; Rabinovich, Alex K.; Rajapakse, Ranjan J.; Truesdale, Larry K.; Tsank, Stella M.; Vazir, Haresh N. [Journal of Organic Chemistry, 2003, vol. 68, # 2, p. 267 - 275]

12
[ 1193-62-0 ]
[ 2491-38-5 ]
methyl 1-[2-(4-hydroxyphenyl)-2-oxoethyl]pyrrole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%		Step 1: To a chilled solution of methyl 1 H-pyrrole-2-carboxylate (1.0 g, 8.0 mmol) in dry DMF (20 ml.) was added sodium hydride (60% in mineral oil, 320 mg, 8.0 mmol)portionwise. The mixture was stirred at 0 C for 1 hour before a solution of 2-bromo-1-(4- hydroxyphenyl)ethanone (780 mg, 3.6 mmol) in DMF (5 ml.) was added. The resulting yellow solution was allowed to warm to room temperature. After 2.5 hours the reaction was complete (monitored by LCMS). A saturated aqueous solution of NH4CI (40 ml.) was added and the mixture was extracted with EtOAc (1 x 20 ml_). The organic layer was concentrated in vacuo to yield a residue that was purified by flash chromatography using the (Biotage SP4, 40 g cartridge, 0 to 100% EtOAc gradient in hexane) to give methyl 1-[2-(4- hydroxyphenyl)-2-oxoethyl]-1 H-pyrrole-2-carboxylate as a white solid (810 mg, yield 87%). 1H-NMR (400 MHz, d6-acetone): delta 3.66 (s, 3H), 5.86 (s, 2H), 6.16 (dd, 1 H, J 3.9, 2.6 Hz), 6.92 (dd, 1 H, J 4.0, 1 .8 Hz), 6.96-7.00 (m, 2H), 7.04-7.06 (m, 1 H), 7.95-8.00 (m, 2H, 9.23 (br s, 1 H).

Reference： [1]Patent: WO2011/94823,2011,A1 .Location in patent: Page/Page column 113
[2]Molecules,2004,vol. 9,p. 574 - 582

13
[ 2491-38-5 ]
[ 56718-71-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 191 - 194

14
[ 2491-38-5 ]
[ 40516-65-2 ]
[ 776312-17-5 ]

Yield	Reaction Conditions	Operation in experiment
84.1%	With sodium hydrogencarbonate In N,N-dimethyl acetamide at 20℃; for 2h;	3-1.1 Example 3-1;5-(4-{4-[4-(1-Propylbutyl)benzyloxy]phenyl}thiazol-2-ylmethoxy)nicotinic acid ; (1) (4-(4-Hydroxyphenyl)thiazol-2-yl)methyl benzoate; [] To a solution of 2-(benzoyloxy)ethanethioamide (4 g, 20.488 mmol) and sodium hydrogen carbonate (1.72 g, 20.488 mmol) in N,N-dimethylacetamide (4 ml) was added dropwise a solution of 2-bromo-4'-hydroxyacetophenone (5 g, purity 88%, 20.488 mmol) in N,N-dimethylacetamide (8 ml) at room temperature, and the mixture was stirred at the same temperature for 2 hr. After the completion of the reaction, ethanol and water were added and the precipitates were collected by filtration and washed with 50% ethanol. The obtained solid was dried under reduced pressure to give the title compound (5.336 g, 84.1%).(2) (4-(4-(4-(1-Propylbutyl)benzyloxy)phenyl)thiazol-2-yl)methyl benzoate

Reference： [1]Current Patent Assignee: JAPAN TOBACCO INC - EP1553091, 2005, A1 Location in patent: Page/Page column 153-154

15
[ 2491-38-5 ]
[ 14140-15-9 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen;palladium 10% on activated carbon; In methanol; for 10h;	To a round bottom flask charged with 4-bromoacetylphenol (4.6 mmol) is added 15 mL methanol. 10 wt % Pd/C (10 wt %, 0.10 g) is then added to it and the mixture is hydrogenated using a balloon filled with hydrogen. The reaction allowed to sit for 10 hours at which time it's filtered through a pad of diatomaceous earth (Celite). The filtrate is then concentrated in vacuo to obtain 4-(2-bromoethyl)phenol as the purified product.

Reference： [1]Patent: US2006/83681,2006,A1 .Location in patent: Page/Page column 11

16
[ 2491-38-5 ]
[ 124-63-0 ]
[ 30095-52-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	With triethylamine In tetrahydrofuran at 0 - 20℃; for 0.5h;	7 Methanesulfonyl chloride (50 g, 436 mmol) was added to a solution of 2-bromo-l-(4-hydroxyphenyl)-ethan-l-one (85 g, 395 mmol) and triethylamine (48g, 474 mmol in tetrahydrofuran (1000 ml) at 0 °C and the mixture was stirred for 30 minutes at room temperature. The mixture was partitioned between water and ethyl acetate, and the organic layer was washed with brine, dried over magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was washed with diisopropyl ether to afford 4-(2_bromoacetyl)phenyl methanesulfonate (96 g, 83%) as white crystals.iH-NMR(CDCl3) 5 : 3.22 (3H, s), 4.41 (2H, s), 7.41 (2H, d, J=7.2 Hz), 8.06 (2H, d, J=7.2 Hz)
83%	With triethylamine In tetrahydrofuran at 0 - 20℃; for 0.5h;	8 Methane sulfonyl chloride (50 g, 436 mmol) was added to a solution of 2-bromo-l'(4-hydroxyphenyl)-ethan-l-one (85 g, 395 mmol) and triethylamine (48g, 474 mmol) in tetrahydrofuran (1000 ml) at 0 0C and the mixture was stirred for 30 minutes at room temperature. The mixture was partitioned between water and ethyl acetate, and the organic layer was washed with brine, dried over magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was washed with diisopropyl ether to afford 4-(2-bromoacetyl)phenyl methanesulfonate (96 g, 83%) as white crystals.IH-NMR(GDCl3) δ 3.22 (3H, s), 4.41 (2H, s), 7.41 (2H, d, J=7.2 Hz), 8.06 (2H, d, J=7.2 Hz)

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION; SANOFI - WO2006/28290, 2006, A1 Location in patent: Page/Page column 77
[2]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION; SANOFI - WO2006/36015, 2006, A2 Location in patent: Page/Page column 135

17
[ 631-58-3 ]
[ 108-20-3 ]
[ 2491-38-5 ]
4-(2-ethyl-4-thiazolyl)-phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.3 parts (40.2%)	In ethanol; water;	EXAMPLE 9 A mixture of 3.6 parts of <strong>[631-58-3]propanethioamide</strong>, 8.6 parts of 2-bromo-1-(4-hydroxyphenyl)ethanone and 79 parts of ethanol was stirred for 7 hours at reflux temperature. The reaction mixture was concentrated to 1/4 of its volume and 2,2'-oxybispropane was added to the residue. The precipitate was filtered off and taken up in water. After basifying with NH4 OH, the product was extracted with dichloromethane. The extract was dried, filtered and evaporated, yielding 3.3 parts (40.2%) of 4-(2-ethyl-4-thiazolyl)-phenol (interm. 17).

Reference： [1]Patent: US5100893,1992,A

18
[ 2491-38-5 ]
[ 7440-44-0 ]
[ 32136-81-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium methylate; In methanol; nitrogen; water; ethyl acetate;	EXAMPLE 4 Preparation of alpha-methoxy-4-hydroxyacetophenone In a nitrogen purged glove bag, 35.06 g (95%; 155 mmol) alpha-bromo-4-hydroxyacetophenone, dissolved in 350 ml methanol, are slowly added to a stirred solution of 69.9 g (91.29 mol) sodium methoxide in 660 ml methanol. About 40 minutes after the addition is complete, a solid (NaBr) precipitates out. After 2 hrs, the dark orange mixture is stripped of solvent. The yellow-orange residue is dissolved in 750 ml water. Once the pH is adjusted to 6, the aqueous solution is extracted by 3*250 ml ethyl acetate; the organic phase is dried over MgSO4 and the solvent is removed by roto-evaporation. The solid is then recrystallized from 180 ml boiling toluene (1.4 g carbon added) to give a light yellow material identified as alpha-methoxy-4-hydroxyacetophenone by GC, 1 H and 13 C NMR.

Reference： [1]Patent: US5107034,1992,A

19
[ 2491-38-5 ]
[ 32136-81-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium hydroxide; In methanol;	EXAMPLE 3 Preparation of alpha-methoxy-4-hydroxyacetophenone 2 g of alpha-bromo-4-hydroxyacetophenone are dissolved in 11 g of methanol. 30 g of a saturated solution of sodium hydroxide in methanol (1 g NaOH/ 4.2 ml methanol) is added dropwise to the alpha-bromo-4-hydroxyacetophenone solution. After the addition is complete, the solution is added to 30 g of ice and acidified to pH 6. Alpha-methoxy-4-hydroxyacetophenone precipitates out and is filtered and dried to a greenish yellow product in about 85% yield; the product is determined by 1-H-NMR to be substantially pure.

Reference： [1]Patent: US5107034,1992,A

20
[ 54326-16-8 ]
2N-hydrochloric acid [ No CAS ]
[ 2491-38-5 ]
5-chloro-1-(4-hydroxyphenacyl)pyrimidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; triethylamine;	EXAMPLE 20 5-Chloro-1-(4-hydroxyphenacyl)pyrimidin-2-one A suspension of <strong>[54326-16-8]5-chloropyrimidin-2-one</strong> (405 mg) and 2-bromo-4'-hydroxyacetophenone (646 mg) in triethylamine (1 ml) and ethanol (20 ml) was stirred at ambient temperature, giving a clear solution. A precipitate had formed after an hour. After 231/2 hours, 2N-hydrochloric acid (5 ml) was added to the suspension and the solid was collected. This was washed with ethanol to give the title pyrimidinone (679 mg,); m.p. 260 with decomposition; lambdamaxEtOH 224 nm (epsilon 17300), 282.5 nm (epsilon 15660), 353 nm (epsilon 4900).

Reference： [1]Patent: US4636509,1987,A

21
[ 2491-38-5 ]
[ 19745-72-3 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 2-bromo-4-hydroxyacetophenone 11 (20.0 mmol) in tetrahydrofuran (THF) (50 mL), hexamethylenetetramine(20.0 mmol) was added and stirred for 3 h at room temperature, and then the precipitated hexamethylenetetramine adduct 12 was filtered out. The adduct 12 was then heated with ethanol (80 mL) and concentrated HCl (8 mL) for 1 h at 45 C. After cooling, the inorganics were filtered out, the mixture was washed with ethanol (20 mL), and the solvent was distilled out completely under reduced pressure to obtain the desired compound 13. Then 14a-d (2.0 mmol), triethylamine (4.0 mmol), and EDCI·HCl (4.0 mmol), followed by HOBT (4.0 mmol), were added to a stirred solution of 13 (2.0 mmol) in CH2Cl2 (10 mL) and the mixture was stirred for 12 h at room temperature. Saturated Na2CO3 was added, the mixture was extracted with ethyl acetate, and the extracts were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by chromatography to give target compounds 15a-d.

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 2550 - 2557
[2]Chemical and Pharmaceutical Bulletin,2015,vol. 63,p. 628 - 635

22
[ 1445-39-2 ]
[ 2491-38-5 ]
[ 956499-77-7 ]

Yield	Reaction Conditions	Operation in experiment
		646 mg (corresponding to 3.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 668 mg (corresponding to 3.0 mmol) of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110C for 8 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 15 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 737 mg (corresponding to 2.19 mmol) of 2-(4'-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyrimidine (Fig. 1-8, Step 2).
		646 mg (corresponding to 3.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 668 mg (corresponding to 3.0 mmol) of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110C for 8 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 15 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 737 mg (corresponding to 2.19 mmol) of 2-(4'-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyrimidine (Fig. 4, Step 2). The NMR measurement results of the resulting 2-(4'-hydroxyphanyl)-6-iodoimidazo[1,2-a]pyrimidine (internal standard: dimethylformamide) are shown below. NMR apparatus employed: JNM-ECP-500 (manufactured by Japan Electron Optics Laboratory Co., Ltd. (JEOL)) 1H-NMR (solvent: dimethylformamide-d7, resonance frequency: 500 MHz): delta 9.80 (br. s, 1H), 9.35 (d, J = 2.3 Hz, 1H), 8.60 (d, J = 2.3 Hz, 1H), 8.23 (s, 1H), 7.94-7.90 (m, 2H), 6.98-6.94 (m, 2H). 13C-NMR (solvent: dimethylformamide-d7, resonance frequency: 125 MHz): delta 158.87, 154.00, 147.18, 146.77, 139.07, 127.68, 124.50, 115.85, 106.10, 73.46.
	With sodium hydrogencarbonate; In methanol; water; acetonitrile;	, Step 1). 646 mg (corresponding to 3.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 668 mg (corresponding to 3.0 mmol) of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110C for 8 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 15 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 737 mg (corresponding to 2.19 mmol) of 2-(4'-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyrimidine (

With sodium hydrogencarbonate; In methanol; water; acetonitrile;

, Step 1). 646 mg (corresponding to 3.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 668 mg (corresponding to 3.0 mmol) of <strong>[1445-39-2]2-amino-5-iodopyrimidine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110C for 8 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 15 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 737 mg (corresponding to 2.19 mmol) of 2-(4'-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyrimidine (

Reference： [1]Patent: EP2019103,2009,A1 .Location in patent: Page/Page column 17
[2]Patent: EP2022792,2009,A1 .Location in patent: Page/Page column 10; 28
[3]Patent: EP2216051,2010,A1
[4]Patent: EP2218463,2010,A1

23
[ 4214-76-0 ]
[ 2491-38-5 ]
[ 956499-89-1 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 5-nitro-pyridin-2-ylamine; 2-bromo-1-(4'-hydroxyphenyl)-1-ethanone In acetonitrile at 110℃; for 6h; Heating / reflux; Stage #2: With sodium hydrogencarbonate In methanol; water for 0.05h; Sonication;	I-10; 8.2 432 mg (corresponding to 2.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 279 mg (corresponding to 2.0 mmol) of 2-amino-5-nitropyridine were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110°C for 6 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 8 mL of water and 8 mL of methanol. Then, about 8 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 148 mg (corresponding to 0.580 mmol) of 2-(4'-hydroxyphenyl)-6-nitroimidazo[1,2-a]pyridine (Fig. 8, Step 2). The NMR measurement results of the resulting 2-(4'-hydroxyphenyl)-6-nitroimidazo[1,2-a]pyridine (internal standard: dimethylsulfoxide) are shown below. NMR apparatus employed: JNM-ECP-500 (manufactured by Japan Electron Optics Laboratory Co., Ltd. (JEOL)) 1H-NMR (solvent: dimethylsulfoxide-d6, resonance frequency: 500 MHz): δ 9.74-9.72 (m, 1H), 9.59 (br. s, 1H), 8.39 (s, 1H), 7.87 (dd, J = 9.9, 2.3 Hz, 1H), 7.79-7.74 (m, 2H), 7.65-7.61 (m, 1H), 6.84-6.80 (m, 2H). 13C-NMR (solvent: dimethylsulfoxide-d6, resonance frequency: 125 MHz): δ 158.47, 148.51, 145.25, 136.63, 127.93, 127.81, 124.06, 118.92, 116.09, 115.92, 110.37.
	With sodium hydrogencarbonate In methanol; water; acetonitrile	1 (ExaropleI-10) Synthesis of 2-(4'-hydroxyphenyl)-6-nitroimidazo[1,2-a]pyridine , Step 1). 432 mg (corresponding to 2.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 279 mg (corresponding to 2.0 mmol) of 2-amino-5-nitropyridine were dissolved in 20 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110°C for 6 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 8 mL of water and 8 mL of methanol. Then, about 8 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 3 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 148 mg (corresponding to 0.580 mmol) of 2-(4'-hydroxyphenyl)-6-nitroimidazo[1,2-a]pyridine (

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); SUMITOMO CHEMICAL COMPANY LIMITED; GENERAL ELECTRIC CO - EP2022792, 2009, A1 Location in patent: Page/Page column 12-13; 29
[2]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; GENERAL ELECTRIC CO; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - EP2216051, 2010, A1

24
[ 2491-38-5 ]
[ 10167-97-2 ]
[ 887576-96-7 ]

Yield	Reaction Conditions	Operation in experiment
		, Step 4). 2.15 g (corresponding to 10.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 1.25 g (corresponding to 10.0 mmol) of <strong>[10167-97-2]2-amino-5-methoxypyridine</strong> were dissolved in 50 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 90°C for 3.5 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 40 mL of water and 40mL of methanol. Then, about 20 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 5 minutes using a ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 1.96 g (corresponding to 8.16 mmol) of 2-(4'-hydroxyphenyl)-6-methoxyimidazo[1,2-a]pyridine ( 2.15 g (corresponding to 10.0 mmol) of 2-bromo-4'-hydroxyacetophenone and 1.25 g (corresponding to 10.0 mmol) of 2-amino-5'-methoxypyridine were dissolved in 50 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 90°C for 3.5 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The recovered precipitates were washed with acetonitrile, and dried under reduced pressure to obtain crude crystals. The resulting crude crystals were suspended in a mixed solution of 40 mL of water and 40mL of methanol. The suspension was supplemented with about 20 mL of a saturated sodium hydrogencarbonate solution, and sonicated for 5 minutes by an ultrasonic washing machine. The precipitates were filtered and recovered from the resulting mixture, washed with water, and dried under reduced pressure, to obtain 1.96 g (corresponding to 8.16 mmol) of 2-(4'-hydroxyphenyl)-6-'methoxyimidazo[1,2-a]pyridine (Fig. 1, Step 5).
		645 mg (corresponding to 3.00 mmol) of 2-bromo-4'-hydroxyacetophenone and 372 mg (corresponding to 3.00 mmol) of <strong>[10167-97-2]2-amino-5-methoxypyridine</strong> were dissolved in 20 mL of acetonitrile. The resulting solution was heated under reflux in an oil bath at 90°C for 2 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure to obtain crude crystals. The resulting crude crystals were suspended in a mixed solution of 4.0 mL of water and 4.0 mL of methanol. Then, about 2.0 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 5 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 512 mg (corresponding to 2.17 mmol) of 2-(4'-hydroxypheny)-6-methoxyimidazo[1,2-a]pyridine (Fig. 9, Step 5).

Reference： [1]Patent: EP2042501,2009,A1 .Location in patent: Page/Page column 8; 15; 24
[2]Patent: EP2213672,2010,A1 .Location in patent: Page/Page column 16; 27

25
[ 288-32-4 ]
[ 2491-38-5 ]
[ 1201802-71-2 ]

Yield	Reaction Conditions	Operation in experiment
59%	With tert-butyldimethylsilyl chloride In formamide at 20℃; for 16h;	123.1 A solution of 2-bromo-1-(4-hydroxyphenyl)ethanone (20 g, 93 mmol) in formamide (75 mL) was heated at 140 °C for 16 h. To the cooled mixture was added imidazole (20 g, 294 mmol), TBS-Cl (31 g, 206 mmol), and DMF (40 mL). The resulting suspension was stirred at rt for 16 h. Water was added and the mixture was extracted with ethyl acetate. The organics were dried (MgSO4) and concentrated. The residue was subject to silica column chromatography (eluting a mixture of DCM:TEA:MeOH 40:2:1) to give 4-(4-[tert- butyl(dimethyl)silyl]oxy}phenyl>1H-rrnidazole (15 g, 59%). LCMS: m/z 275.2 (M+H)+.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2009/152025, 2009, A1 Location in patent: Page/Page column 77

26
[ 2491-38-5 ]
[ 1147550-11-5 ]
[ 56430-88-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	Stage #1: ammonium thiocyanate With montmorillonite K₁₀ clay In acetone at 20℃; for 0.666667h; Stage #2: 2-bromo-1-(4'-hydroxyphenyl)-1-ethanone at 20℃; for 0.00833333h; Neat (no solvent); Grinding;	General procedure for the preparation of K10-montmorillonite clay supported ammonium thiocyanate; General procedure for the synthesis of α-oxo thiocyanates by using K10-montmorillonite clay supported ammonium thiocyanate under catalyst and solvent free conditions In a round bottomed 500 ml flask equipped with stir bar and containing 100 ml acetone, was added 7.6 g of ammonium thiocyanate salt and stirred at room temperature until the complete dissolution of salt. To this clear solution, 10 g of montmorillonite K10 clay was added in portions over 10 min with stirring. After complete addition, the formation of reddish suspension was observed which was vigorously stirred for another 30 min at room temperature. Then the suspension is placed in a rotary vacuum evaporator and the solvent was removed under reduced pressure. The dry solid crust adhering to the walls of the flask was flaked off with a spatula, and solvent evaporation was resumed. After complete drying, yielded, about 17.6 g of clay supported ammonium thiocyanate as a light red free flowing powder which shows no loss of reactivity after standing in an open powder box for one week.; Phenacyl bromide (1 mmol) and K10-montmorillonite clay supported ammonium thiocyanate (3 mmol) were taken in mortar, mixed with spatula, and ground with pestle for stipulated time (see Table 3). After complete conversion as indicated by TLC, the solid reaction mixture was directly loaded on silica gel column by avoiding aqueous work up-extraction step. Later elution with ethyl acetate-hexane (9:1-3:1) solvent system and evaporation of solvents in rotary vacuum evaporator afforded pure phenacyl thiocyanate (99%). Same procedure as discussed above was followed to prepare all thiocyanate compounds shown in this work. All compounds prepared were characterized by IR, Mass, and NMR spectroscopy.
	In dichloromethane at 20℃;

Reference： [1]Location in patent: experimental part Meshram; Thakur, Pramod B.; Madhu Babu; Bangade, Vikas M. [Tetrahedron Letters, 2012, vol. 53, # 14, p. 1780 - 1785]
[2]Location in patent: experimental part Bhalerao, Dinesh S.; Akamanchi, Krishnacharya G. [Synthetic Communications, 2010, vol. 40, # 6, p. 799 - 807]

27
[ 98198-48-2 ]
[ 2491-38-5 ]
[ 1147549-07-2 ]

Yield	Reaction Conditions	Operation in experiment
		2.00 g (corresponding to 9.28 mmol) of 2-bromo-4'-hydroxyacetophenone and 1.91 g (corresponding to 10.2 mmol) of <strong>[98198-48-2]2-amino-5-bromo-4-methylpyridine</strong> were dissolved in 40 mL of acetonitrile. The resulting solution was heated under reflux in an oil bath at 110C for 3 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 50 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 10 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 2.67 g (corresponding to 8.81 mmol) of 6-bromo-2-[4'-hydroxyphenyl]-7-methylimidazo[1,2-a]pyridine (Fig. 9, Step 2).

Reference： [1]Patent: EP2213671,2010,A1 .Location in patent: Page/Page column 13; 26

28
[ 2491-38-5 ]
[ 40615-39-2 ]
[ 1335224-05-9 ]

Yield	Reaction Conditions	Operation in experiment
69.7%	Stage #1: 5'-O-(4-4'-dimethoxytrityl)thymidine With lithium hexamethyldisilazane In tetrahydrofuran for 0.416667h; Inert atmosphere; Stage #2: 2-bromo-1-(4'-hydroxyphenyl)-1-ethanone In tetrahydrofuran at 20℃; for 18h; Inert atmosphere;	1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenyl-methoxy]methyl]-4-[2-(4-hydroxyphenyl)-2-oxo-ethoxy]tetrahydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione (3). To a round bottom flask was added 1 (10.06g, 18.5mmol) in 150mL dry THF under argon. LiHMDS (40 mL, 1.0M solution in THF) was added via syringe over 5 min. After stirring for 20 min, 2 (9.94g, 46.2mmol) was added at once and the mixture was allowed to stir for 18 hours at rt. TLC analysis (45% EtOAc in Hexanes, Rf = 0.53) shows the reaction to be complete. The mixture was quenched with MeOH and evaporated under reduced pressure, then dissolved in 100 mL EtOAc and washed with H2O (4 x 20mL). The organic layer was dried over MgSO4, and evaporated under vacuum. The resulting dark brown oil was purified by flash chromatography (10-100% EtOAc in hexanes over 20 CV) to yield a colorless oil (8.74g, 69.7%).

Reference： [1]Pickens, Chad J.; Gee, Kyle R. [Tetrahedron Letters, 2011, vol. 52, # 39, p. 4989 - 4991]

29
[ 2491-38-5 ]
[ 1233329-45-7 ]
[ 1233330-73-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With I₂ In ethyl acetate	25 Preparation of (R)-1-(2-(4-hydroxyphenyl)-2-oxoethyl)-3-((R)-2-phenyl-2-(phenylamino)acetoxy)-1-azoniabicyclo[2.2.2]octane bromide (Diastereomer 1 of I71) Preparation of (R)-1-(2-(4-hydroxyphenyl)-2-oxoethyl)-3-((R)-2-phenyl-2-(phenylamino)acetoxy)-1-azoniabicyclo[2.2.2]octane bromide (Diastereomer 1 of I71) 2-Bromo-1-(4-hydroxyphenyl)ethanone (256 mg, 1.19 mmol) was added to a solution of (R)-((R)-quinuclidin-3-yl) 2-phenyl-2-(phenylamino)acetate (diastereomer 1 of I2) (400 mg, 1.19 mmol) in EtOAc (15 ml). The resulting reaction was stirred at room temperature for 15 hours. The solvent was removed under vacuum, and the residue was triturated with Et2O to obtain (R)-1-(2-(4-hydroxyphenyl)-2-oxoethyl)-3-((R)-2-phenyl-2-(phenylamino)acetoxy)-1-azoniabicyclo[2.2.2]octane bromide (655 mg, 100% yield).
100%	In ethyl acetate at 20℃; for 15h;	25 2-Bromo- 1 -(4-hydroxyphenyl)ethanone (256 mg, 1.19 mmol) was added to a solution of ( )-(( )-quinuclidin-3-yl) 2-phenyl-2-(phenylamino)acetate (diastereomer 1 of 12) (400 mg, 1.19 mmol) in EtOAc (15 ml). The resulting reaction was stirred at room temperature for 15 h. The solvent was removed under vacuum and the residue was triturated with Et2O to obtain (R)-l-(2-(4- hydroxyphenyl)-2-oxoethyl)-3-((R)-2-phenyl-2-(phenylamino)acetoxy)-l- azoniabicyclo[2.2.2]octane bromide (655 mg, 100% yield).

Reference： [1]Current Patent Assignee: Valline SRL - US2011/311458, 2011, A1
[2]Current Patent Assignee: Valline SRL - WO2011/161018, 2011, A1 Location in patent: Page/Page column 71

30
[ 2491-38-5 ]
[ 2752-65-0 ]
4-(2-bromoacetyl)phenyl gambogate [ No CAS ]

Reference： [1]Molecules,2012,vol. 17,p. 6249 - 6268

31
[ 2491-38-5 ]
[ 99-56-9 ]
[ 1415328-10-7 ]

Yield	Reaction Conditions	Operation in experiment
93.6%	In dimethyl sulfoxide at 20℃;	2 A mixture of 2-bromo-1-(4-hydroxyphenyl)ethanone (1 mmol) and 4-nitrobenzene-1,2-diamine (1 mmol) was stirred in 5 mL DMSO at room temperature. The reaction mixture was poured into water, and quickly filtered over a buchner funnel. The filter residue was washed with water, oven dried and purified by silica gel chromatography (petroleum ether/ethylacetate = 2:1), to give 250 mg of 1 in a yield of 93.6%. 1H NMR (400 MHz, [D6]-DMSO) δ 10.27 (s, 1H), 9.68 (d, J = 4.5 Hz, 1H), 8.81 (dd, J = 13.2, 2.5 Hz, 1H), 8.50 (dd, J = 9.2, 2.6 Hz, 1H), 8.29 (d, J = 8.8 Hz, 2H), 8.23 (t, J = 9.0 Hz, 1H), 6.98 (d, J = 8.7 Hz, 2H), 5.37 (s, 1H). MS (ESI) m/z calcd for C14H9N3O3 267.1, found 267.7 [M + H]+.
58%	In dimethyl sulfoxide at 20℃; for 10h;	1 Example 1: Synthesis of Intermediate 1 The compound 4-nitro-o-phenylenediamine (3.1g, 20.0mmol) was dissolved in a 250mL round bottom flask with 8mL DMSO, and then 2-bromo-4'-hydroxyacetophenone (4.3g, 20.0mmol) was slowly Add to the reaction flask and stir at room temperature for 10 hours. After the reaction is complete, a yellow solid precipitates out. The precipitated product is suction filtered and washed with 100 mL of deionized water and 50 mL of methanol. The solid obtained by suction filtration is dried. 3.1g Intermediate 1, with a yield of 58.0%, and the structure is as follows:lh
58%	In dimethyl sulfoxide at 20℃; for 0.166667h;

Reference： [1]Yu, Pingrong; Cui, Mengchao; Wang, Xuedan; Zhang, Xiaojun; Li, Zijing; Yang, Yanping; Jia, Jianhua; Zhang, Jinming; Ono, Masahiro; Saji, Hideo; Jia, Hongmei; Liu, Boli [European Journal of Medicinal Chemistry, 2012, vol. 57, p. 51 - 58]
[2]Current Patent Assignee: BEIJING NORMAL UNIVERSITY - CN108047145, 2020, B Location in patent: Paragraph 0033; 0040; 0041
[3]Zhou, Kaixiang; Yang, Fan; Li, Yuying; Chen, Yimin; Zhang, Xiaojun; Zhang, Jinming; Wang, Junfeng; Dai, Jiapei; Cai, Lisheng; Cui, Mengchao [Molecular Pharmaceutics, 2021, vol. 18, # 3, p. 1176 - 1195]

32
[ 96-50-4 ]
[ 2491-38-5 ]
[ 1448788-76-8 ]

Yield	Reaction Conditions	Operation in experiment
83%	With 1,4-diaza-bicyclo[2.2.2]octane In water at 60 - 70℃; for 4h; Green chemistry; regioselective reaction;	General procedure General procedure: The mixture of phenacyl bromide (1 mmol), 2-aminopyridine (1 mmol) and DABCO (10 mol %) was stirred in water (5 mL) at 60-70 °C for 1 h. The reaction was monitored by TLC. After the completion of the reaction, it was extracted with ethyl acetate (3 × 5 mL). The combined organic layer washed with brine solution, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude products were purified by silica gel column chromatography (ethyl acetate/hexane, 1:10). All compounds were characterized by mp, NMR, mass, HRMS and IR spectral data

Reference： [1]Bangade, Vikas M.; Reddy, B. Chennakesava; Thakur, Pramod B.; Madhu Babu; Meshram [Tetrahedron Letters, 2013, vol. 54, # 35, p. 4767 - 4771]

33
[ 2491-38-5 ]
[ 487-70-7 ]
[ 446-72-0 ]

Yield	Reaction Conditions	Operation in experiment
75%		General procedure: To prepare catalyst, 0.21 g of thiamine hydrochloride (0.6 mmol) was dissolved in 0.64 mL of water and added 2.4 mLof 95% ethanol (water : 95% ethanol = ~1:4). The solution was cooled in an ice bath, then added 0.40 mL of 3 M NaOH(1.2 mmol) dropwise with stirring in a manner such that thetemperature remained below 20 C. Intense yellow coloured solution changed to pale yellow solution of thiamine (thiazolium ion)/N-heterocyclic carbene (Scheme 1).47 In a 25-mL round bottom flask, a mixture of phenacylbromide 1 (2.5 mmol, 0.5 g in case of 1a) and thiamine (0.6 mmol, 25 mol %) in ethanol (4 mL) was stirred at room temperature for 15 min. Then, salicylaldehyde 2 (2.5 mmol, 0.26 mL in case of 2a) was added slowly and the mixture was stirred at room temperature until the reaction was completed (as monitored by TLC) (Table 3) . The reaction mixture was then poured into 20 mL of distilled water and extracted with ethyl acetate (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The resulting product isoflavone 3 was further purified either by recrystallizationor by column chromatography (Ethyl acetate:Hexane, 1:4v/v). All compounds were characterized by their mp and 1HNMR, 13CNMR and mass spectral data.

Reference： [1]Bulletin of the Korean Chemical Society,2013,vol. 34,p. 1070 - 1076

34
[ 2491-38-5 ]
[ 95-01-2 ]
[ 486-66-8 ]

Yield	Reaction Conditions	Operation in experiment
82%		General procedure: To prepare catalyst, 0.21 g of thiamine hydrochloride (0.6 mmol) was dissolved in 0.64 mL of water and added 2.4 mLof 95% ethanol (water : 95% ethanol = ~1:4). The solution was cooled in an ice bath, then added 0.40 mL of 3 M NaOH(1.2 mmol) dropwise with stirring in a manner such that thetemperature remained below 20 C. Intense yellow coloured solution changed to pale yellow solution of thiamine (thiazolium ion)/N-heterocyclic carbene (Scheme 1).47 In a 25-mL round bottom flask, a mixture of phenacylbromide 1 (2.5 mmol, 0.5 g in case of 1a) and thiamine (0.6 mmol, 25 mol %) in ethanol (4 mL) was stirred at room temperature for 15 min. Then, salicylaldehyde 2 (2.5 mmol, 0.26 mL in case of 2a) was added slowly and the mixture was stirred at room temperature until the reaction was completed (as monitored by TLC) (Table 3) . The reaction mixture was then poured into 20 mL of distilled water and extracted with ethyl acetate (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The resulting product isoflavone 3 was further purified either by recrystallizationor by column chromatography (Ethyl acetate:Hexane, 1:4v/v). All compounds were characterized by their mp and 1HNMR, 13CNMR and mass spectral data.

Reference： [1]Bulletin of the Korean Chemical Society,2013,vol. 34,p. 1070 - 1076

35
[ 673-22-3 ]
[ 2491-38-5 ]
[ 486-63-5 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 2-bromo-1-(4'-hydroxyphenyl)-1-ethanone With thiamine hydrochloride In ethanol at 20℃; for 0.25h; Green chemistry; Stage #2: 2-Hydroxy-4-methoxybenzaldehyde In ethanol at 20℃; for 1.46667h; Green chemistry;	Experimental General procedure: To prepare catalyst, 0.21 g of thiamine hydrochloride (0.6 mmol) was dissolved in 0.64 mL of water and added 2.4 mLof 95% ethanol (water : 95% ethanol = ~1:4). The solution was cooled in an ice bath, then added 0.40 mL of 3 M NaOH(1.2 mmol) dropwise with stirring in a manner such that thetemperature remained below 20 °C. Intense yellow coloured solution changed to pale yellow solution of thiamine (thiazolium ion)/N-heterocyclic carbene (Scheme 1).47 In a 25-mL round bottom flask, a mixture of phenacylbromide 1 (2.5 mmol, 0.5 g in case of 1a) and thiamine (0.6 mmol, 25 mol %) in ethanol (4 mL) was stirred at room temperature for 15 min. Then, salicylaldehyde 2 (2.5 mmol, 0.26 mL in case of 2a) was added slowly and the mixture was stirred at room temperature until the reaction was completed (as monitored by TLC) (Table 3) . The reaction mixture was then poured into 20 mL of distilled water and extracted with ethyl acetate (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The resulting product isoflavone 3 was further purified either by recrystallizationor by column chromatography (Ethyl acetate:Hexane, 1:4v/v). All compounds were characterized by their mp and 1HNMR, 13CNMR and mass spectral data.

Reference： [1]Mishra, Priya; Singh, Sarita; Ankit, Preyas; Fatma, Shahin; Singh, Divya; Singh, Jagdamba [Bulletin of the Korean Chemical Society, 2013, vol. 34, # 4, p. 1070 - 1076]

36
[ 1194-98-5 ]
[ 2491-38-5 ]
6-hydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: 2-bromo-1-(4'-hydroxyphenyl)-1-ethanone With thiamine hydrochloride In ethanol at 20℃; for 0.25h; Green chemistry; Stage #2: 2,5-Dihydroxybenzaldehyde In ethanol at 20℃; for 1.41667h; Green chemistry;	Experimental General procedure: To prepare catalyst, 0.21 g of thiamine hydrochloride (0.6 mmol) was dissolved in 0.64 mL of water and added 2.4 mLof 95% ethanol (water : 95% ethanol = ~1:4). The solution was cooled in an ice bath, then added 0.40 mL of 3 M NaOH(1.2 mmol) dropwise with stirring in a manner such that thetemperature remained below 20 °C. Intense yellow coloured solution changed to pale yellow solution of thiamine (thiazolium ion)/N-heterocyclic carbene (Scheme 1).47 In a 25-mL round bottom flask, a mixture of phenacylbromide 1 (2.5 mmol, 0.5 g in case of 1a) and thiamine (0.6 mmol, 25 mol %) in ethanol (4 mL) was stirred at room temperature for 15 min. Then, salicylaldehyde 2 (2.5 mmol, 0.26 mL in case of 2a) was added slowly and the mixture was stirred at room temperature until the reaction was completed (as monitored by TLC) (Table 3) . The reaction mixture was then poured into 20 mL of distilled water and extracted with ethyl acetate (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The resulting product isoflavone 3 was further purified either by recrystallizationor by column chromatography (Ethyl acetate:Hexane, 1:4v/v). All compounds were characterized by their mp and 1HNMR, 13CNMR and mass spectral data.

Reference： [1]Mishra, Priya; Singh, Sarita; Ankit, Preyas; Fatma, Shahin; Singh, Divya; Singh, Jagdamba [Bulletin of the Korean Chemical Society, 2013, vol. 34, # 4, p. 1070 - 1076]

37
[ 2491-38-5 ]
[ 387-46-2 ]
[ 148356-24-5 ]

Yield	Reaction Conditions	Operation in experiment
82%		General procedure: To prepare catalyst, 0.21 g of thiamine hydrochloride (0.6 mmol) was dissolved in 0.64 mL of water and added 2.4 mLof 95% ethanol (water : 95% ethanol = ~1:4). The solution was cooled in an ice bath, then added 0.40 mL of 3 M NaOH(1.2 mmol) dropwise with stirring in a manner such that thetemperature remained below 20 C. Intense yellow coloured solution changed to pale yellow solution of thiamine (thiazolium ion)/N-heterocyclic carbene (Scheme 1).47 In a 25-mL round bottom flask, a mixture of phenacylbromide 1 (2.5 mmol, 0.5 g in case of 1a) and thiamine (0.6 mmol, 25 mol %) in ethanol (4 mL) was stirred at room temperature for 15 min. Then, salicylaldehyde 2 (2.5 mmol, 0.26 mL in case of 2a) was added slowly and the mixture was stirred at room temperature until the reaction was completed (as monitored by TLC) (Table 3) . The reaction mixture was then poured into 20 mL of distilled water and extracted with ethyl acetate (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The resulting product isoflavone 3 was further purified either by recrystallizationor by column chromatography (Ethyl acetate:Hexane, 1:4v/v). All compounds were characterized by their mp and 1HNMR, 13CNMR and mass spectral data.

Reference： [1]Bulletin of the Korean Chemical Society,2013,vol. 34,p. 1070 - 1076

38
[ 2491-38-5 ]
[ 20816-46-0 ]

Yield	Reaction Conditions	Operation in experiment
96%	With silver(I) acetate In N,N-dimethyl-formamide at 50℃; for 3h; Inert atmosphere; Darkness;	General procedure for acetoxylation of alkyl halides with AgOAc. General procedure: To a suspension of AgOAc (0.25 mmol) in MeCN or DMF (2 mL) was added the alkylhalide (0.25 mmol) dissolved in 1 mL of the corresponding solvent. The reaction mixture was stirred at the temperature indicated on table 1 until starting material was consumed. After that, a saturated solution of NH4Cl (20 mL) was added and the crude mixture was extracted three times with EtOAc (3 x 15 mL). When necessary, the product was purifiedby column chromatography (hexane/EtOAc).

Reference： [1]Nolla-Saltiel, Roberto; Carrillo-Arcos, Ulises Alonso; Porcel, Susana [Synthesis, 2014, vol. 46, # 2, p. 165 - 169]

39
[ 2491-38-5 ]
[ 4619-20-9 ]
[ 79-19-6 ]
[ 1476801-87-2 ]

Yield	Reaction Conditions	Operation in experiment
78%		General procedure: Absolute EtOH (20 mL), ketoacid (10 mmol), 0.2 g activated KSF, and thiosemicarbazide(10 mmol) were added to a 100-ml round-bottom flask equipped withcondenser and magnetic stir bar. The reaction mixture was refluxed for the requiredreaction time (about 7 h). The progress of reaction was monitored by thin-layer chromatography(TLC) (EtOAc-petroleum ether 2:1). After completion of the reaction,phenacyl bromide (10 mmol) was added and refluxed for the required reaction time(about 2 h). The progress of the reaction was monitored by TLC (EtOAc-petroleumether 1:2). The catalyst was removed by filtration. The reaction solution was cooledto rt. The product was isolated by filtration and purified by washing with EtOH.

Reference： [1]Synthetic Communications,2014,vol. 44,p. 245 - 250

40
[ 2491-38-5 ]
[ 3984-34-7 ]
[ 79-19-6 ]
[ 1476801-89-4 ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: 4-(4-chlorophenyl)-4-oxobutanoic acid; thiosemicarbazide With montmorillonite KSF In ethanol for 0.7h; Reflux; Stage #2: 2-bromo-1-(4'-hydroxyphenyl)-1-ethanone In ethanol for 0.2h; Reflux; regioselective reaction;	General Procedure for the Synthesis of 2-(Thiazol-2-yl)-4,5-dihydropyridazin-3(2H)-one General procedure: Absolute EtOH (20 mL), ketoacid (10 mmol), 0.2 g activated KSF, and thiosemicarbazide(10 mmol) were added to a 100-ml round-bottom flask equipped withcondenser and magnetic stir bar. The reaction mixture was refluxed for the requiredreaction time (about 7 h). The progress of reaction was monitored by thin-layer chromatography(TLC) (EtOAc-petroleum ether 2:1). After completion of the reaction,phenacyl bromide (10 mmol) was added and refluxed for the required reaction time(about 2 h). The progress of the reaction was monitored by TLC (EtOAc-petroleumether 1:2). The catalyst was removed by filtration. The reaction solution was cooledto rt. The product was isolated by filtration and purified by washing with EtOH.

Reference： [1]Mahmoodi, Nosrat O.; Safari, Niloufar; Sharifzadeh, Bahman [Synthetic Communications, 2014, vol. 44, # 2, p. 245 - 250]

41
[ 2491-38-5 ]
[ 6340-79-0 ]
[ 79-19-6 ]
[ 1476801-90-7 ]

Yield	Reaction Conditions	Operation in experiment
82%		General procedure: Absolute EtOH (20 mL), ketoacid (10 mmol), 0.2 g activated KSF, and thiosemicarbazide(10 mmol) were added to a 100-ml round-bottom flask equipped withcondenser and magnetic stir bar. The reaction mixture was refluxed for the requiredreaction time (about 7 h). The progress of reaction was monitored by thin-layer chromatography(TLC) (EtOAc-petroleum ether 2:1). After completion of the reaction,phenacyl bromide (10 mmol) was added and refluxed for the required reaction time(about 2 h). The progress of the reaction was monitored by TLC (EtOAc-petroleumether 1:2). The catalyst was removed by filtration. The reaction solution was cooledto rt. The product was isolated by filtration and purified by washing with EtOH.

Reference： [1]Synthetic Communications,2014,vol. 44,p. 245 - 250

42
[ 2491-38-5 ]
[ 6324-72-7 ]
[ 1595280-32-2 ]

Yield	Reaction Conditions	Operation in experiment
59.3%	With sodium hydroxide In water at 20℃; for 1h;	2 General procedure for the preparation of compounds 3-9 and 12-17 General procedure: In a round bottom flask equipped with a stir bar was dissolved 2-amino-6-hydroxy-8-mercaptopurine (1-2 mmol, 1.0 equiv) in aqueous sodium hydroxide (0.4 N, 10 mL) and corresponding phenyl substituted 2-bromoacetophenones (1.25-2.5 mmol,1.25 equiv) dissolved in EtOH (2 mL) was added. The mixtures were stirred for 1 h at room temperature before the solution was neutralized by drop wise addition of HCl (1 N) to yield aprecipitate. The precipitate was collected via vacuum filtration,washed with diethyl ether and verified to be pure via LC-MS and1H NMR.

Reference： [1]Yun, Mi-Kyung; Hoagland, Daniel; Kumar, Gyanendra; Waddell, M. Brett; Rock, Charles O.; Lee, Richard E.; White, Stephen W. [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 7, p. 2157 - 2165]

43
[ 2491-38-5 ]
[ 3696-23-9 ]
[ 825661-01-6 ]

Yield	Reaction Conditions	Operation in experiment
62%	In ethanol at 80℃; for 0.5h; Microwave irradiation;	4 General procedure: A solution of 150 mg (0.64 mmol) 2-bromo-1-(4-chlorophenyl)-ethanone (B, Scheme 2 ) and 126 mg (0.64 mmol) 1-(benzo[d][1,3]dioxol-5-yl)thiourea (E, Scheme 2 ) in 2 ml ethanol was heated to 80 °C for 30 min under microwave irradiation. The precipitated white hydrobromide salt was collected, washed with H2O and cold ethanol, yield: 182 mg (69%).

Reference： [1]Rödl, Carmen B.; Vogt, Dominik; Kretschmer, Simon B.M.; Ihlefeld, Katja; Barzen, Sebastian; Brüggerhoff, Astrid; Achenbach, Janosch; Proschak, Ewgenij; Steinhilber, Dieter; Stark, Holger; Hofmann, Bettina [European Journal of Medicinal Chemistry, 2014, vol. 84, p. 302 - 311]

44
[ 2491-38-5 ]
[ 459-05-2 ]
[ 1622931-26-3 ]

Yield	Reaction Conditions	Operation in experiment
83%	In ethanol at 80℃; for 0.5h; Microwave irradiation;	4 General procedure: A solution of 150 mg (0.64 mmol) 2-bromo-1-(4-chlorophenyl)-ethanone (B, Scheme 2 ) and 126 mg (0.64 mmol) 1-(benzo[d][1,3]dioxol-5-yl)thiourea (E, Scheme 2 ) in 2 ml ethanol was heated to 80 °C for 30 min under microwave irradiation. The precipitated white hydrobromide salt was collected, washed with H2O and cold ethanol, yield: 182 mg (69%).

45
[ 14222-60-7 ]
[ 2491-38-5 ]
[ 1046045-54-8 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 6572 - 6582

46
[ 2491-38-5 ]
[ 17356-08-0 ]
[ 57634-55-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In water; for 0.333333h;Reflux;	General procedure: 2-amino-4-aryl thiazole derivatives were prepared19-21using different substituted phenacyl bromides by refluxing with excess thiourea in presence of conc. HClfor about 20 min. After the completion of reaction, thereaction mixture was cooled to room temperature; thepale yellow solid thus separated was filtered, washedwith chloroform, dried and recrystallized from ethanolto obtain 2-amino-4-aryl thiazole derivatives.

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 3068 - 3087
[2]Journal of Chemical Sciences,2014,vol. 126,p. 1913 - 1921
[3]Journal of the Chinese Chemical Society,2017,vol. 64,p. 1408 - 1416

47
[ 461-88-1 ]
[ 2491-38-5 ]
4-(7-aminoimidazo[1,2-a]pyridin-2-yl)phenol hydrobromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18%	In acetone; at 65℃;Inert atmosphere; Sealed tube;	Example 3a) 4-(7-Aminoimidazo[1,2-a]pyridin-2-yl)phenol hydrobromideIn a 5 mL microwave vial, <strong>[461-88-1]pyridine-2,4-diamine</strong> (500 mg, 4.58 mmol) and 2-bromo-l-(4- hydroxyphenyl)ethanone (1.03 g, 4.81 mmol) were combined with acetone (8.0 mL) to give an off-white suspension. The vial was flushed with argon and closed. The reaction mixture was stirred at 65 C ( oil bath temperature) overnight. The off-white suspension was filtered and washed with acetone. The resulting off-white solid was dried under high vacuum overnight to afford the title compound (363 mg, 18 % yield) as an off-white solid. MS m/z: 226.1 [M+H]+

Reference： [1]Patent: WO2015/44095,2015,A1 .Location in patent: Page/Page column 13

48
[ 2491-38-5 ]
5-phenyloctahydrocyclopenta[c]pyrrole [ No CAS ]
1-(4-hydroxyphenyl)-2-(5-phenylhexahydrocyclopenta[c]pyrrol-2(1H)-yl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 4h;	13.1 Step-1: l-(4-hydroxyphenyl)-2-(5-phenylhexahydrocyclopenta[c]pyrrol-2(lH)- yl)ethanone Step-1: l-(4-hydroxyphenyl)-2-(5-phenylhexahydrocyclopenta[c]pyrrol-2(lH)- yl)ethanone [0146] To a stirred solution of 5-phenyloctahydrocyclopenta[c]pyrrole (0.3 g, 1.60 mmol) in dimethylformamide (10 mL) was added potassium carbonate (0.44 g, 3.20 mmol) and 2-bromo-l-(4-hydroxyphenyl)ethanone (0.34 g, 1.60 mmol) at room temperature and the reaction mixture was stirred for 4 h. After completion of reaction (monitored by TLC), the reaction mixture was diluted with cold water (25 mL) and extracted with ethylacetate (50 mL x 3). The combined organic layer was washed with cold water (25 ml x 3), brine (25 mL) dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to afford the crude compound which was purified by silica gel column chromatography (30% ethyl acetate/hexane) to obtain the title compound l-(4-hydroxyphenyl)-2-(5- phenylhexahydrocyclopenta[c]pyrrol-2(lH)-yl)ethanone (0.3 g, 63 % yield) as a pale yellow solid. Calculated (M+H): 322.27; Found (M+H): 322.2.

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2015/48507, 2015, A1 Location in patent: Paragraph 0146

49
[ 172739-04-7 ]
[ 2491-38-5 ]
2-(5-benzylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-1-(4-hydroxyphenyl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With potassium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 2h;	53.1 Step 1: Preparation of 2-(5-benzylhexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)-l-(4- hydroxyphenyl)ethanone Step 1: Preparation of 2-(5-benzylhexahydropyrrolo[3,4-c]pyrrol-2(lH)-yl)-l-(4- hydroxyphenyl)ethanone [0215] 2-bromo-l-(4-hydroxyphenyl) ethanone (0.107 g, 0.494 mmol) was added to a mixture of commercially available 2-benzyloctahydropyrrolo[3,4-c]pyrrole (0.1 g, 0.494 mmol) and potassium carbonate (0.2 g, 1.48 mmol) in DMF (5 mL) at 0 °C and the reaction mixture was stirred at room temperature for 2 h. The suspension was filtered and the filtrate was evaporated. The crude material was purified by combi flash purifier using 8 % methanol in dichloromethane to afford the title compound 2-(5-benzylhexahydropyrrolo[3,4-c]pyrrol- 2(lH)-yl)-l-(4-hydroxyphenyl)ethanone (0.12 g, 72 % yield) as a white solid. Calculated M+H: 337.43; Found M+H: 337.2.

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2015/48507, 2015, A1 Location in patent: Paragraph 0215

50
[ 2491-38-5 ]
[ 42017-89-0 ]
2-(4-hydroxyphenyl)-2-oxoethyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In tetrahydrofuran; at 20℃; for 4h;	General procedure: CDI (10.0 mmol) was dissolved in N,N-dimethylformamide (DMF) (20 mL) and to this solution a solution of the carboxylic acids 14a and d (10.0 mmol) in DMF (2 mL) was added dropwise. Subsequently, the reaction mixture was stirred at room temperature for 1 h. Then, H2S was bubbled gently through the reaction mixture for 2 h. Sulfuric acid (0.5 M, 40 mL) was added and the mixture was extracted with ethyl acetate. The organic layer was dried with magnesium sulfate (MgSO4), filtered, and concentrated to yield 16a ,d, 14a, d, 16a, and d (2.0 mmol). They were dissolved in THF (10 mL), anhydrous K2CO3 (4.0 mmol) and 2-bromo-4-hydroxyacetophenone 11 (2.0 mmol) were added, and the mixture was stirred for 4 h at room temperature. Dilute HCl was added, and the mixture was extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered, and concentrated, and the residue was purified by chromatography to afford target compounds 17a, d, 18a, and d.

Reference： [1]Chemical and Pharmaceutical Bulletin,2015,vol. 63,p. 628 - 635

51
[ 2491-38-5 ]
[ 25812-30-0 ]
2-(4-hydroxyphenyl)-2-oxoethyl 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In tetrahydrofuran; at 20℃; for 4h;	General procedure: CDI (10.0 mmol) was dissolved in N,N-dimethylformamide (DMF) (20 mL) and to this solution a solution of the carboxylic acids 14a and d (10.0 mmol) in DMF (2 mL) was added dropwise. Subsequently, the reaction mixture was stirred at room temperature for 1 h. Then, H2S was bubbled gently through the reaction mixture for 2 h. Sulfuric acid (0.5 M, 40 mL) was added and the mixture was extracted with ethyl acetate. The organic layer was dried with magnesium sulfate (MgSO4), filtered, and concentrated to yield 16a ,d, 14a, d, 16a, and d (2.0 mmol). They were dissolved in THF (10 mL), anhydrous K2CO3 (4.0 mmol) and 2-bromo-4-hydroxyacetophenone 11 (2.0 mmol) were added, and the mixture was stirred for 4 h at room temperature. Dilute HCl was added, and the mixture was extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered, and concentrated, and the residue was purified by chromatography to afford target compounds 17a, d, 18a, and d. 2-(4-Hydroxyphenyl)-2-oxoethyl-5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoate (17a): Yield 83%, mp 105.6-108.3 C. 1H-NMR (400 MHz, CDCl3) delta: 1.32 (6H, s), 1.81-1.85 (4H, m),2.18 (3H, s), 2.30 (3H, s), 3.94-3.97 (2H, m), 5.23 (2H, s), 5.62(1H, s), 6.63-6.66 (2H, m), 6.85-6.87 (2H, m), 6.98-7.00 (1H,d, J=7.6 Hz), 7.80-7.82 (2H, m). ESI-MS m/z: 385 [M+H]+.
3.21 g		A mixture of <strong>[25812-30-0]gemfibrozil</strong> (2.50 g, 10.0 mmol)And K2CO3 (1.37 g, 10.0 mmol)Was added to tetrahydrofuran (30 mL)After stirring at room temperature for 0.5 h,To the stirred solution was added alpha-bromo-p-hydroxyacetophenone (2.15 g, 10.0 mmol)In tetrahydrofuran (10 mL),Continue stirring for 12 h.Spin out the solvent,Dilute hydrochloric acid acidification,Ethyl acetate (25 mL x 3) was added,Organic phase with water,Dried over anhydrous sodium sulfate,The filtrate was separated and purified by silica gel column chromatography.Intermediate2- (4-hydroxyphenyl) -2-oxo-ethyl-5- (2,5-dimethylphenoxy) -2,2-dimethyl-pentanoic acid 3.21g,

Reference： [1]Molecular Diversity,2018,p. 1 - 15
[2]Chemical and Pharmaceutical Bulletin,2015,vol. 63,p. 628 - 635
[3]Patent: CN106478452,2017,A .Location in patent: Paragraph 0056; 0057

52
[ 2491-38-5 ]
[ 4254-67-5 ]

Reference： [1]Journal of Organic Chemistry,2015,vol. 80,p. 9713 - 9721
[2]Journal of Organic Chemistry,2015,vol. 80,p. 9713 - 9721

53
[ 2491-38-5 ]
[ 37904-72-6 ]
[ 79-40-3 ]
[ 39696-20-3 ]
C₂₂H₂₂N₄S₂ [ No CAS ]
C₂₀H₁₇N₃OS₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol;Reflux;	A one-step combinatorial approach for synthesis of the bithiazoles was performed in ethanol The mixture of three possible products was purified by means of flash chromatography or preparative HPLC.

Reference： [1]Patent: WO2016/1422,2016,A1 .Location in patent: Page/Page column 25

54
[ 2491-38-5 ]
[ 100-39-0 ]
[ 4254-67-5 ]

Yield	Reaction Conditions	Operation in experiment
43%	With silver carbonate; In tetrahydrofuran; at 0 - 20℃; for 16h;	Step 1: Preparation of l-(4-(benzyloxy)phenyl)-2-bromoethanone [00170] To a solution of 2-bromo- 1 -(4-hydroxyphenyl)ethanone (2 g, 9.3 mmol) in tetrahydrofuran (70 mL) was added silver carbonate (5.128 g, 18.6 mmol) and the reaction mixture was cooled to 0 C. Benzyl bromide (1.32 m L, 11.16 mmol) was added drop wise and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was filtered through celite, the filtrate was diluted with ethyl acetate (200 mL) and washed with water (60 mL x 2). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude was purified by column chromatography using 6% ethyl acetate in hexane to afford title l-(4-(benzyloxy)phenyl)-2-bromoethanone (1.22 g, 43% yield) as a white solid. Calculated M+H: 306.17; Found M+H: 306.

Reference： [1]Patent: WO2016/49165,2016,A1 .Location in patent: Paragraph 00170

55
[ 15761-39-4 ]
[ 2491-38-5 ]
1-(tert-butyl) 2-(2-(4-hydroxyphenyl)-2-oxoethyl) (S)-pyrrolidine-1,2-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 5h;	5.1.1.14 1-(tert-Butyl) 2-(2-(4-hydroxyphenyl)-2-oxoethyl) (S)-pyrrolidine-1,2-dicarboxylate (10a) 2-Bromo-4-hydroxyacetophenone 9a (1.00g, 4.65mmol) and N-Boc-l-proline (1.10g, 5.12mmol) in Acetonitrile (50mL) put into the flask. Diisopropylethylamine (1.44mL, 5.58mmol) was added dropwise to the mixture and was stirred at room temperature for 5h. The mixture was then poured in 1N aq HCl solution and extracted with CH2Cl2. The organic layer dried over magnesium sulfate, and then was purified by the column chromatography (n-hexane/ethyl acetate). The residue 10a was obtained as white solid (1.20g, 74%). 1H NMR (DMSO-d6, δ=2.5ppm, 400MHz): 10.49 (s, 1H), 7.86-7.85 (d, 2H), 6.88-6.86 (t, 2H), 5.53-5.32 (m, 2H), 4.32-4.29 (m, 1H), 3.11 (m, 2H), 2.29-2.14 (m, 2H), 1.90-1.85 (m, 2H), 1.36 (app br s, 9H). 13C NMR (DMSO-d6, δ=39.52ppm, 100MHz): 190.5, 172.3, 162.7, 153.0, 130.4, 125.4, 115.4, 78.9, 66.1, 58.6, 46.2, 30.4, 27.9, 23.1. HRMS (ESI) m/z: Anal. calcd. for [M+Na]+ C18H23NNaO6: 372.1418; found 372.1419.
74%	With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 5h;	21 Preparation of (S)-1-tert-butyl 2-(2-(4-hydroxyphenyl)-2-oxoethyl)pyrrolidine-1,2-dicarboxylate 2-Bromo-4-hydroxyacetophenone (1.00 g, 4.65 mmol) And N-Boc-L-proline (1.10 g, 5.12 mmol) Was dissolved in acetonitrile (50 mL) Diisopropylethylamine (1.44 mL, 5.58 mmol) was added portionwise, And the mixture was stirred at room temperature for 5 hours. The reaction mixture was diluted with 1 N aqueous hydrochloric acid solution and extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and then concentrated in vacuo. The residue was purified by silica gel flash column chromatography using hexane: ethyl acetate as mobile phase to give the desired compound (1.20 g, 74% yield) as a white solid.
74%	With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 5h;

Reference： [1]You, Youngsu; Kim, Hee Sun; Bae, Il Hak; Lee, Seung Gi; Jee, Min Hyeok; Keum, Gyochang; Jang, Sung Key; Kim, B. Moon [European Journal of Medicinal Chemistry, 2017, vol. 125, p. 87 - 100]
[2]Current Patent Assignee: POHANG UNIVERSITY OF SCIENCE AND TECHNOLOGY; SEOUL NATIONAL UNIVERSITY - KR2017/31307, 2017, A Location in patent: Paragraph 0262-0264
[3]You, Youngsu; Kim, Hee Sun; Park, Jung Woo; Keum, Gyochang; Jang, Sung Key; Kim, B. Moon [RSC Advances, 2018, vol. 8, # 55, p. 31803 - 31821]

56
[ 2491-38-5 ]
[ 7659-07-6 ]
2-(4-fluorophenyl)-6-(4-hydroxyphenyl)imidazo[2,1-b]-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44.2%	In ethanol; for 0.00694444h;Microwave irradiation; Green chemistry;	1) added to the drying in the crucible 0.01mol abromo-p-hydroxyacetophenone, 0.01mol 2-amino-5-(pfluorophenyl)-1,3,4-oxadiazole is dissolved in anhydrous ethanol, get mixed solution A1, to a crucible of the reaction liquid is placed in the microwave oven, power modulation high fire files 700W, opening microwave oven radiation 25 seconds after the closing, of the crucible is taken out of the glass rod for stirring cooling, every 5 to detect reaction TLC (developing agent to volume ratio is: dichloromethane: methanol =10:1 mixture); 2) if the crucible is ethanol volatilizes in adding ethanol, to TLC detection reaction is complete, add water to the reaction solution of 15 ml, then the saturated NaOH solution for pH value adjusted to 7-8, to get mixed solution B1; 3) the mixture solution B1off the solvent, the crude product obtained after water washing, filtering, drying and recrystallized with absolute ethanol, to obtain 2 - (4-fluoro phenyl) - 6 - (4-hydroxy-phenyl)-imidazo [2,1-b] - 1, 3, 4-oxadiazole, yield 44.2%,

Reference： [1]Patent: CN105418636,2016,A .Location in patent: Paragraph 0052; 0053; 0054; 0055; 0056

57
[ 5871-17-0 ]
[ 2491-38-5 ]
C₂₀H₂₃O₇PS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium carbonate In acetonitrile at 20℃; for 3h;	1 The thioether containing phosphotriester represents the synthesis of the compound TEEP-OH 1, 0.42 g (2 mmol) of 0,0-diethyl phosphorothioate was dispersed in 50 mL of acetonitrile and gradually added0.868 (4 ure 1) 2-bromo-4-light-acetophenone and 1.388 (101111] 101) potassium carbonate solid; the reaction was continuously stirred at room temperatureThin layer chromatography (TLC) point plate observation reaction is complete. Thereafter, the reaction solvent was distilled off under reduced pressure, and the mixture was washed with 50 mL of ethyl acetate and50 mL of water, the organic phase was collected by extraction, washed three times with 50 mL of water, and then washed with anhydrous sulfuric acidSodium was dried, and finally the ethyl acetate was removed under reduced pressure to give the product ΕΕΡ-0Η (structure and rearrangement mechanism shown in Figure 4), light yellow solidThe bulk powder was 0.81 g, yield 92%

Reference： [1]Current Patent Assignee: TSINGHUA UNIVERSITY (CHINA) - CN105524104, 2016, A Location in patent: Paragraph 0025; 0026; 0015

58
[ 5871-17-0 ]
[ 2491-38-5 ]
C₁₂H₁₇O₅PS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium carbonate In acetonitrile at 20℃; for 0.25h;	2 Synthesis of Comparative Compound DEPT-OH Compound In order to compare with the product of Example 1, the raw materials in Example 1 were prepared at a ratio of 1: 1Reaction: 0.42 g (2 mmol) of potassium 0,0-diethyl phosphorothioate was dispersed in 50 mL of acetonitrile, and gradually 0.43 g(21111) 1 0 1) 2-bromo-4-light-acetophenone and 0.698 (51] 11] 101) potassium carbonate solid; reaction at room temperature under stirring 151]Thin layer chromatography (TLC) point plate observation reaction is complete. Thereafter, the reaction solvent was distilled off under reduced pressure, and the mixture was washed with 50 mL of ethyl acetate and50 mL of water, the organic phase was collected by extraction, washed three times with 50 mL of water, and then washed with anhydrous sulfuric acidSodium was dried, and finally the ethyl acetate was removed under reduced pressure to give the product DEPT-HH (structure and reaction flow shown in Figure 4), white powder0.548, yield 89%

Reference： [1]Current Patent Assignee: TSINGHUA UNIVERSITY (CHINA) - CN105524104, 2016, A Location in patent: Paragraph 0015; 0027; 0028

59
[ 2491-38-5 ]
[ 25812-30-0 ]
[ 57260-73-8 ]
C₃₃H₄₀N₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.64 g		<strong>[25812-30-0]Gemfibrozil</strong> lg,Dicyclohexylcarbodiimide 1.07 g,1-Boc ethylenediamine 0.64 g,Dichloromethane 60ml placed in a single mouth bottle 100ml,The reaction was carried out at room temperature for 4 hours. The residue was recrystallized from ethanol and evaporated to dryness to give 1.44 g of a white solid, 50 ml of a single-necked flask, 20 ml of methylene chloride and 4 ml of trifluoroacetic acid,After 1 hour, lmol / L potassium carbonate aqueous solution to adjust pH to alkaline,The organic layer was dried,The solvent was evaporated,Ethanol recrystallization,Obtained as a white solid. 94 g,50ml single-mouth bottle,2-Bromo-1- (4-hydroxyphenyl) ethanone (1.37 g)Potassium carbonate 3.5 g,TLC was used to monitor the reaction end point,Column chromatography gave 1.64 g of the title compound

Reference： [1]Patent: CN103087009,2016,B .Location in patent: Paragraph 0091; 0092

60
[ 2491-38-5 ]
[ 41859-67-0 ]
C₂₇H₂₆ClNO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.93 g	With potassium carbonate; In tetrahydrofuran; at 20℃; for 3.5h;	<strong>[41859-67-0]Bezafibrate</strong> lg,0.6 g of 2-bromo-1- (4-hydroxyphenyl) ethanone,0.84 g of potassium carbonate, 50 ml of tetrahydrofuran,The reaction was carried out at room temperature for 3.5 hours, and the filtrate was evaporated to dryness to afford the desired compound (0.93 g)

Reference： [1]Patent: CN103087009,2016,B .Location in patent: Paragraph 0105; 0106

61
[ 2491-38-5 ]
[ 41859-67-0 ]
C₂₇H₂₆ClNO₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.7 g		<strong>[41859-67-0]Bezafibrate</strong> 1g,0.49 g of N, N-carbonyldiimidazole (CDI)N, N-dimethylformamide (DMF)Stirring at room temperature 4h, access to hydrogen sulfide gas,After 20 minutes, the solvent was evaporated to dryness, 20 ml of ethyl acetate was added,Cold dilute aqueous solution of hydrochloric acid 20ml,The organic layer was dried, concentrated and evaporated to dryness to give a yellow solid.2-bromo-1- (4-hydroxyphenyl) ethanone,Potassium carbonate 0.84 g,The yellow crude product obtained above,Tetrahydrofuran (50 ml)Room temperature reaction,3 hours,The filtrate was evaporated to dryness to afford 0.7 g of the title compound

Reference： [1]Patent: CN103087009,2016,B .Location in patent: Paragraph 0109; 0110

62
[ 461-88-1 ]
[ 2491-38-5 ]
4-(7-aminoimidazo[1,2-a]pyridin-2-yl)phenol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 7350 - 7370

63
[ 2491-38-5 ]
[ 149-30-4 ]
2-(benzo[d]thiazol-2-ylthio)-1-(4-hydroxyphenyl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With zinc(II) oxide In neat (no solvent) at 25 - 30℃;
72%	Stage #1: 2-Mercaptobenzothiazole With sodium hydroxide In methanol at 20℃; for 0.166667h; Stage #2: 2-bromo-1-(4'-hydroxyphenyl)-1-ethanone In methanol at 20℃;	2.2. A general synthesis method of the compounds 1-6 [28] (Figure 2) General procedure: Mercapto-based compounds (9.3 mmol) [Benzo[d]thiazole-2-thiol for 1 (1.6 g), 1H- benzo[d]oxazole-2-thiolfor 2 (1.43 g), 1-methyl-1H-imidazole-2-thiol for 3 (1.1 g), 5-methyl-1,3,4-thiadiazole-2-thiol for 4 (1.23 g),4-methyl-4H-1,2,4-triazole-3-thiol for 5 (1.1 g), 1-methyl-1H-tetrazole-5-thiol for 6 (1.1 g)] was dissolved at room temperature in fresh methanolic NaOH solution (0.4 g, 25 mL methanol) and stirred for 10 min. Then,2-bromo-4’-hydroxyacetophenone (9.3 mmol, 2 g) was put into the reaction flask. After the final mixture was stirred for several hours at room temperature, it was taken into the water (50 mL). The white solid obtained was filtered, washed with water three times, and then dried. The compounds were purified by crystallization using suitable solvents such as ethanol (1-4, 6 ) and ethanol: DMF (5). 2.2.1. 2-(Benzo[d]thiazol-2-ylthio)-1-(4-hydroxyphenyl)ethanone, 1Mp = 188-189 °C. Yield 72%. IR (KBr) cm-1 : 3209, 3061, 3019, 2959, 2914, 1660, 1575, 1414, 1202, 1169,993, 829, 753, 725. 1 H NMR (400 MHz, DMSO - d6, δ , ppm) 7.99 - 7.93 (m, 3H, ArH), 7.76 (d, J = 7.7 Hz,1H, ArH), 7.44 - 7.39 (m, 1H, ArH), 7.35 - 7.31 (m, 1H, ArH), 6.86 (d, J = 8.2 Hz, 2H, ArH), 5.06 (s, 2H,-CH2 -). 13 C NMR (100 MHz, DMSO - d6, δ , ppm) 191.5 (C=O), 166.8, 163.4, 153.2, 135.4, 131.9, 127.5,127.0, 125.1, 122.5, 121.7, 116.1, 41.4 (-CH2 -). Predicted [M + H] + 302.0304; measured [M + H] + 302.0311.

Reference： [1]Md. Khaja Mohinuddin; Gangi Reddy [European Journal of Organic Chemistry, 2017, vol. 2017, # 8, p. 1207 - 1214]
[2]Demir, Yeliz; Gülçin, Ilhami; Gül, Halise Inci; Kazaz, Cavit; Yamali, Cem [Turkish Journal of Chemistry, 2020, vol. 44, # 4, p. 1058 - 1067]

64
[ 5346-38-3 ]
[ 2491-38-5 ]
[ 764623-45-2 ]

Reference： [1]Archiv der Pharmazie,2018,vol. 351

65
[ 2491-38-5 ]
[ 4919-43-1 ]
C₁₉H₁₅NO₄ [ No CAS ]

Reference： [1]RSC Advances,2018,vol. 8,p. 15009 - 15020

66
[ 623-73-4 ]
[ 2491-38-5 ]
ethyl (2-(4-hydroxyphenyl)-2-oxoethyl) oxalate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With oxygen; eosin y In N,N-dimethyl-formamide at 20℃; for 36h; Schlenk technique; Irradiation;
79%	With oxygen; eosin y In N,N-dimethyl-formamide for 36h; Irradiation; Schlenk technique; Green chemistry;	11 Embodiment 11 Compound 1k (0.5 mmol, 113.2 mg), compound 2a (2 mmol, 224 vL), was added to a 25 mL Schlenk tube. Eosin Y (0.005 mol, 3.6 mg), N,N-dimethylformamide (2 mL). The system was then reacted for 36 hours in the presence of a 12 W green LED lamp in oxygen. After completion of the reaction, it was extracted with ethyl acetate (10 mL × 3) and dried over anhydrous magnesium sulfate. The solvent was removed by a rotary evaporator, and the silica gel was adsorbed. The product 3k was obtained by simple column chromatography with a yield of 79%.

Reference： [1]Ma, Meihua; Hao, Weiwei; Ma, Liang; Zheng, Yonggao; Lian, Pengcheng; Wan, Xiaobing [Organic Letters, 2018, vol. 20, # 18, p. 5799 - 5802]
[2]Current Patent Assignee: SOOCHOW UNIVERSITY (SUZHOU) - CN108863777, 2018, A Location in patent: Paragraph 0039

67
[ 2491-38-5 ]
[ 171820-09-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With ammonium acetate; sodium hydroxide In water; dimethyl sulfoxide at 110℃; for 1h; chemoselective reaction;	A typical reaction procedure for the synthesis of pyrazine derivatives General procedure: The reactions were conducted in a 10mL of V-type flask equipped with triangle magnetic stirring. In a typical reaction, 1a (0.20mmol) was mixed with 2a (0.24mmol) and NaOH (0.2mmol) in DMSO (V)/H2O (V)=50/1,. The mixture was then stirred at 110°C for one hour. After reaction, the reaction was quenched by water (5mL), solution was subsequently extracted by ethyl acetate (3×5mL). After extraction, organic phase was combined, removed solvent by rotate evaporation. The final product was obtained by column chromatography. Tests for substrate scope were all performed with an analogous procedure.

Reference： [1]Liu, Changhui; Zhao, Jiateng; Qiao, Yu; Huang, Wenbo; Rao, Zhonghao; Gu, Yanlong [Tetrahedron, 2018, vol. 74, # 51, p. 7351 - 7357]

68
[ 2491-38-5 ]
[ 39809-25-1 ]
3-(4-hydroxy-3-(hydroxymethyl)butyl)-6-(4-hydroxyphenyl)-3,5-dihydro-9H-imidazo[1,2-a]purin-9-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%		General procedure: To a suspension of penciclovir (6) or hydroxybutylguanine (7)(0.2 g, 0.8 mmol or 0.9 mmol, respectively) in dry dimethylformamide(16 mL), sodium hydride (60% suspension in mineral oil, 1.2 eq.) wasadded and the reaction stirred at room temperature (21 C) for 1.5 h.Bromoketone (8) (1.3 eq.) was then added and the reaction stirred for6 h. Aqueous ammonia (25% solution 5 mL) was added to quench thereaction, which was concentrated under reduced pressure and the residualoil purified by flash column chromatography using gradientelution (CH2Cl2-MeOH). The obtained products were recrystallisedfrom a mixture of CH2Cl2 and MeOH.

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 1023 - 1033

69
[ 2491-38-5 ]
[ 1612-76-6 ]
4-(2-phenylimidazo[2,1-b][1,3,4]oxadiazol-5-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70.4%	In ethanol for 0.416667h; Microwave irradiation;	The microwave method General procedure: The 2-Amino-5-aryl-1,3,4-oxadiazole (0.01 mol), α-bromoacetophenones derivatives (0.01 mol) and catalyst were treated by a microwave system for about the appropriate time. The microwave-accelerated reaction system was operated at 200 W. The progress of the reaction was monitored by TLC using dichloromethane/methanol (10:1) as eluent. After completion of the reaction, the solution pH was adjusted to 7-8. The crude product thus obtained was filtered, and recrystallized from N,N-Dimethylformamide to get the compounds (1a-1v).

Reference： [1]Liu, Yuting; Dang, Yang; Yin, Dawei; Yang, Lan; Zou, Qian [Research on Chemical Intermediates, 2019, vol. 45, # 10, p. 4907 - 4926]

70
[ 2491-38-5 ]
[ 7659-07-6 ]
4-[2-(4-fluorophenyl)-6-piperazin-1-ylmethylimidazo[2,1-b][1,3,4]oxadiazol-5-yl]phenol [ No CAS ]

Reference： [1]Research on Chemical Intermediates,2019,vol. 45,p. 4907 - 4926

71
[ 2491-38-5 ]
[ 7659-07-6 ]
4-[2-(4-fluorophenyl)imidazo[2,1-b][1,3,4]oxadiazol-5-yl]phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72.3%	In ethanol; for 0.333333h;Microwave irradiation;	General procedure: The 2-Amino-5-aryl-1,3,4-oxadiazole (0.01 mol), α-bromoacetophenones derivatives (0.01 mol) and catalyst were treated by a microwave system for about the appropriate time. The microwave-accelerated reaction system was operated at 200 W. The progress of the reaction was monitored by TLC using dichloromethane/methanol (10:1) as eluent. After completion of the reaction, the solution pH was adjusted to 7-8. The crude product thus obtained was filtered, and recrystallized from N,N-Dimethylformamide to get the compounds (1a-1v).

Reference： [1]Research on Chemical Intermediates,2019,vol. 45,p. 4907 - 4926

72
[ 4144-22-3 ]
[ 2491-38-5 ]
2-(tert-butyl)-8-hydroxy-3a,9b-dihydro-1H-benzo[e]isoindole-1,3,5(2H,4H)-trione [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 6270 - 6274

73
[ 2491-38-5 ]
[ 95-54-5 ]
C₁₄H₁₉N₂O₂⁽¹⁺⁾*Br^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With 1,4-diaza-bicyclo[2.2.2]octane In tetrahydrofuran at 20℃; for 1h;	Pathway A Pathway A. A mixture of o-phenylenediamine (1) (1 mmol), 2-bromo-1-(4-hydroxyphenyl)ethanone (2) (1mmol) and DABCO (20% mol) in THF (20 ml) was stirred at room temperature for 1 hr.44 The solid residue wascollected and proved to be the quaternary salt 5.2-(4-Bromo-1l4,4l4-diazabicyclo[2.2.2]octan-1-yl)-1-(4-hydroxyphenyl)ethan-1-one quaternary salt (5)Colorless powder (83%); mp > 300 C; IR (KBr) u 3417, 2987, 1681, 1597, 1458 cm-1; 1H NMR (300 MHz, DMSOd6)δ 3.12 (t, 6H, CH2N, J = 6.9 Hz), 3.60 (t, 6H, CH2N, J = 7.2 Hz), 5.14 (s, 2H, COCH2N), 7.12 (d, 2H, ArH, J = 8.7Hz), 7.87 (d, 2H, ArH, J = 6.6 Hz), 10.81 (s, 1H, OH); MS m/z (%) 326 (M+). Anal. Calcd for C14H19BrN2O2: C,51.39; H, 5.85; Br, 24.42; N, 8.56. Found: C, 51.48; H, 5.71; Br, 24.35; N, 8.44%.

Reference： [1]Abd El-Fatah, Nesma A.; Darweesh, Ahmed F.; Salem, Mostafa E.; Abdelhamid, Ismail A.; Elwahy, Ahmed H.M. [Arkivoc, 2019, vol. 2019, # 6, p. 252 - 266]

74
[ 2491-38-5 ]
[ 89226-13-1 ]
tert-butyl N-[[4-(4-hydroxyphenyl)thiazol-2-yl]methyl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	In ethanol; at 20℃; for 12h;	To a solution of 2-bromo-1-(4-hydroxyphenyl)ethan-1-one (1.5 g, 6.97 mmol) in EtOH (30 mL) was added <strong>[89226-13-1]tert-butyl (2-amino-2-thioxoethyl)carbamate</strong> (1.3 g, 6.97 mmol) at room temperature. The mixture was stirred 12 h then concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 30-40% EtOAc in petroleum ether affording an off white solid (900 mg, 42%). M/z 307.1 (M+H)+.

Reference： [1]Patent: EP3628672,2020,A1 .Location in patent: Paragraph 0272-0274

75
[ 2491-38-5 ]
[ 38942-52-8 ]
1-(4-hydroxyphenyl)-2-((4-isopropyl-4H-1,2,4-triazol-3-yl)thio)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	In ethanol at 90℃;	General procedure for synthesis of final products (Z9, 7-24) General procedure: The suspension of bromide 6 (8.0mmol, 1.0 eq) and thiol (8.0mmol, 1.0 equiv.) in anhydrous EtOH (30mL) was stirred at 90°C for 18h. The reaction mixture was cooled to room temperature and the forming precipitate was filtered off, yielding the pure product. If necessary, the product was purified by flash chromatography.

Reference： [1]Fonović, Urša Pečar; Gobec, Stanislav; Hrast, Martina; Knez, Damijan; Kos, Janko; Proj, Matic; Zidar, Nace [European Journal of Medicinal Chemistry, 2020, vol. 193]

76
3-(2-((4-methoxyphenyl)amino)ethyl)-4-phenyl-1H-1,2,4-triazole-5(4H)-thione [ No CAS ]
[ 2491-38-5 ]
1-(4-hydroxyphenyl)-2-((5-(2-((4-methoxyphenyl)amino)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With potassium carbonate In acetone at 40℃; for 3h;	Method C. General procedure: To triazolethione 8 (0.49 g, 1.5 mmol) dissolved in acetone (15 mL), K2CO3 (1 g, 7.2 mmol) and corresponding halocarbonyl compound (2 mmol) were added. The reaction mixture was stirred at 40 °C for 3 h. Afterwards water (20 mL) was added, the precipitate formed was isolated by filtration, and recrystallized from propan-2-ol.

Reference： [1]Jonuškienė, Ilona; Kantminienė, Kristina; Klevinskas, Arnas; Mickevičius, Vytautas; Petrikaitė, Vilma; Tumosienė, Ingrida [Molecules, 2020, vol. 25, # 13]

77
[ 2491-38-5 ]
6-(benzo[d][1,3]dioxol-5-ylmethyl)-5-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one [ No CAS ]
6-(benzo[d][1,3]dioxol-5-ylmethyl)-2-((2-(4-hydroxyphenyl)-2-oxoethyl) thio)-5-methylpyrimidin-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With potassium carbonate In N,N-dimethyl-formamide at 20℃;	4.4 General synthesis of 5-alkyl-6-(benzo[d][1,3]dioxol-5-alkyl)-2-mercapto-pyrimidin-4(3H)-ones (5a-5w) General procedure: K2CO3 (0.3g, 2.2mmol) and R2Br (2.2mmol) were added to a solution of (benzo[d][1,3]dioxol-5-alkyl)-5-alkyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones 11a-11d (2mmol) in anhydrous DMF (8mL). The mixture was stirred at room temperature for 8-24h. After TLC revealed the disappearance of the starting material, the reaction mixture was filtered. The suspension was then diluted with cold water (150mL) and extracted with EtOAc (3×50mL). The combined organic extract was washed with brine (3×50mL), dried with Na2SO4, and evaporated to furnish crude product, which was purified by flash chromatography or by crystallization to give the pure target compounds 5a-5w.
	Stage #1: 6-(benzo[d][1,3]dioxol-5-ylmethyl)-5-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: 2-bromo-1-(4'-hydroxyphenyl)-1-ethanone In N,N-dimethyl-formamide at 20℃; for 2h;	2 General procedure: Combine 6-(1,3-benzodioxy-5-methyl)-2-mercapto-5-ethyl-3H-pyrimidin-4-one) (S-DABOs reactant) (3mmol) and K2CO3( 3.6mmol) was placed in a round-bottomed flask, added 5ml of anhydrous dimethylformamide (DMF), stirred at room temperature for 1h, added brominated side chain reactant (3.3mmol), stirred at room temperature for 2h, when TLC (Thin-layer chromatographic analysis) The reaction is stopped after tracking to the disappearance of the raw material point. Pour the reaction solution into 100ml ice water, back-extract three times with EA (ethanol) (50ml×3), combine the organic layers, wash three times with water (50ml×3), and then wash three times with saturated brine (50ml×3). Finally, it was dried with anhydrous Na2SO4 to obtain the crude product of the target compound, which was purified by column chromatography or recrystallized with acetone/petroleum ether, ethyl acetate/petroleum ether or methanol/chloroform system to obtain 6-(1,3-benzodioxy- 5-(methyl)yl)-substituted uracil derivative compounds 1a to 1w are pure products. The purification steps are: column chromatography purification or recrystallization. The solvent is the volume ratio in the column chromatography purification operation.Recrystallization operation: dissolve the compound sample with solvent A, then add solvent B until the resulting solution is turbid and stop adding solvent B. After standing still, a large amount of precipitate is deposited.

Reference： [1]Cui, Yi-Man; He, Yan-Ping; Huang, Si-Ming; Li, Sui-Yuan; Li, Xiao-Li; Li, Yi-Ming; Luo, Rong-Hua; Ni, Dong-Xuan; Tang, E.; Xiao, Wei-Lie; Yang, Liu-Meng; Zhang, Hong-Bin; Zhang, Rui-Han; Zhang, Xing-Jie; Zheng, Yong-Tang; Zheng, Yu-Gui [Bioorganic Chemistry, 2020, vol. 102]
[2]Current Patent Assignee: YUNNAN UNIVERSITY; CHINESE ACADEMY OF SCIENCES - CN111303136, 2020, A Location in patent: Paragraph 0099-0107

78
[ 2491-38-5 ]
6-(benzo[d][1,3]dioxol-5-ylmethyl)-5-ethyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one [ No CAS ]
6-(benzo[d][1,3]dioxol-5-ylmethyl)-5-ethyl-2-((2-(4-hydroxyphenyl)-2-oxoethyl)thio)pyrimidin-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With potassium carbonate In N,N-dimethyl-formamide at 20℃;	4.4 General synthesis of 5-alkyl-6-(benzo[d][1,3]dioxol-5-alkyl)-2-mercapto-pyrimidin-4(3H)-ones (5a-5w) General procedure: K2CO3 (0.3g, 2.2mmol) and R2Br (2.2mmol) were added to a solution of (benzo[d][1,3]dioxol-5-alkyl)-5-alkyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones 11a-11d (2mmol) in anhydrous DMF (8mL). The mixture was stirred at room temperature for 8-24h. After TLC revealed the disappearance of the starting material, the reaction mixture was filtered. The suspension was then diluted with cold water (150mL) and extracted with EtOAc (3×50mL). The combined organic extract was washed with brine (3×50mL), dried with Na2SO4, and evaporated to furnish crude product, which was purified by flash chromatography or by crystallization to give the pure target compounds 5a-5w.

79
[ 2491-38-5 ]
6-(1,3-benzodioxy-5-yl)-2-mercapto-5-ethyl-3H-pyrimidin-4-one [ No CAS ]
6-(benzo[d][1,3]dioxol-5-yl)-5-ethyl-2-((2-(4-hydroxyphenyl)-2-oxoethyl)thio)pyrimidin-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With potassium carbonate In N,N-dimethyl-formamide at 20℃;	4.4 General synthesis of 5-alkyl-6-(benzo[d][1,3]dioxol-5-alkyl)-2-mercapto-pyrimidin-4(3H)-ones (5a-5w) General procedure: K2CO3 (0.3g, 2.2mmol) and R2Br (2.2mmol) were added to a solution of (benzo[d][1,3]dioxol-5-alkyl)-5-alkyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones 11a-11d (2mmol) in anhydrous DMF (8mL). The mixture was stirred at room temperature for 8-24h. After TLC revealed the disappearance of the starting material, the reaction mixture was filtered. The suspension was then diluted with cold water (150mL) and extracted with EtOAc (3×50mL). The combined organic extract was washed with brine (3×50mL), dried with Na2SO4, and evaporated to furnish crude product, which was purified by flash chromatography or by crystallization to give the pure target compounds 5a-5w.

80
[ 2491-38-5 ]
[ 60-56-0 ]
1-(4-hydroxyphenyl)-2-((1-methyl-1H-imidazol-2-yl)thio)ethanone [ No CAS ]