Name: 486-66-8|7-Hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one|98%
Brand: Ambeed
SKU: A129224
Price: 10.0 USD
Availability: InStock
Rating: 96 (29 reviews)

1
[ 486-66-8 ]
[ 108-24-7 ]
[ 3682-01-7 ]

Yield	Reaction Conditions	Operation in experiment
98%		General procedure: <strong>[486-66-8]Daidzein</strong> (1) or chrysin (7) (8 mmol) was dissolved in acetic anhydride (30 mL), and was stirredat 60 C for 10 min. Dry pyridine (8 mL) was added dropwise to the stirred mixture at 60 C. After5 min, a white precipitate appeared. After 2 h, the reaction mixture was poured onto ice and stirredfor an hour. The formed white precipitate was filtered out, and washed with water thoroughly. Afterdrying above potassium hydroxide for 2 days, the crude products were recrystallized from ethanol.7-Acetoxy-3-(4-acetoxyphenyl)-4H-chromen-4-one (2): white crystals (98%);
96.5%	for 3h;Reflux;	Synthesis of diacetyl <strong>[486-66-8]daidzein</strong> (2) (0113) A mixture of <strong>[486-66-8]daidzein</strong> (2.54 g, 10 mmol) and acetic anhydride (5 ml) was stirred at reflux for 3 hours until a clear solution formed. After cooling isopropanol (20 ml was added and the suspension was stirred for 1 hour at r.t. The precipitate of 2 was filtered off, washed with isopropanol and dried on air. The yield of compound 2 was 3.26 g (9.65 mmol, 96.5%).A mixture of <strong>[486-66-8]daidzein</strong> (2.54 g, 10 mmol) and acetic anhydride (5 ml) was stirred at reflux for 3 hours until a clear solution formed. After cooling isopropanol (20 ml was added and the suspension was stirred for 1 hour at r.t. The precipitate of 2 was filtered off, washed with isopropanol and dried on air. The yield of compound 2 was 3.26 g (9.65 mmol, 96.5%).
90%	With pyridine; at 105 - 110℃; for 1h;	Method B A mixture of <strong>[486-66-8]daidzein</strong> (2.0 g, 7.9 mmol), acetic anhydride (10 ml) and pyridine (2 ml) was heated on an oil bath at 105-110 C for 1 h. After cooling the mixture to room temperature, it was stirred for a further 30 min during which time the diacetate crystallized from the solution.

84.15%	With sulfuric acid; In 1,2-dichloro-ethane; at 60℃; for 4h;	To wash and dry 1000ml reaction flask into 50g (0.1968mol) <strong>[486-66-8]daidzein</strong>, 300g1,2- dichloroethane, 95g (0.93213mol) acetic anhydride and 12g of concentrated sulfuric acid.Cast was completed, the reaction temperature was raised to 75 3h, the reaction was completed, vacuum recovery of 1,2-dichloroethane, recovery has been completed, the residue was added to the anti-ice mixture, a lot of precipitation and crystallization, filtration, drying, class white solid 55.98g.That is, the compound (B).Yield: 84.15%
83%	With pyridine; at 20℃; for 24h;	Example 14',7 diacetoxy<strong>[486-66-8]daidzein</strong>Method AA mixture of <strong>[486-66-8]daidzein</strong> (1.0 g, 3.9 mmol), acetic anhydride (5 ml) and pyridine (5 ml) was left in the dark at room temperature for 24 h. The reaction mixture was poured into water (100 ml), stirred for 2 h and then extracted with dichloromethane (3x50 ml). The dichloromethane layer was washed with water, dried over anhydrous sodium sulfate and evaporated. The white residue was crystallised from methanol to yield <strong>[486-66-8]daidzein</strong> diacetate as white prisms (1.1 g, 83%). 1H NMR (CDCl3): ? 2.32 (s, 3H, OCOCH3), 2.36 (s, 3H, OCOCH3), 7.18 (d, 2H, J 9.2 Hz, ArH), 7.19 (d, 1H, J 9.0 Hz, H6), 7.31 (d, 1H, J 20 Hz H8), 7.59 (d, 2H, J 9.2 Hz, ArH), 8.00 (s, 1H, H2), 8.33 (d, 2H, J 8.2 Hz, ArH).
74.9%	With pyridine;Reflux;	General procedure: To solution of apigenin (3mmol) in acetic anhydride (6mL) was added pyridine (0.6mL). Then, the mixture was heated to reflux until apigenin consumption and was poured into ice-cold water (70mL) to afford 4 as a white solid. The crude product was recrystallized to get pure compound. Compounds 5, 12 and 13 were synthesized according to the method for 4. 4.1.3.3 4', 7- O-diacetyl<strong>[486-66-8]daidzein</strong> (12) Compound 12 was recrystallized from ethyl acetate. Yield 74.9%; White solid. 1H NMR (400 MHz, CDCl3) delta 8.32 (d, 1H, J = 8.0 Hz, H-5), 8.01 (s, 1H, H-2), 7.58 (d, 2H, J = 8.0 Hz, H-2', H-6'), 7.31 (d, 1H, J = 2.0 Hz, H-8), 7.19-7.16 (m, 3H, H-6, H-3', H-5'), 2.36 (s, 3H, -OCOCH3), 2.32 (s, 3H, -OCOCH3).

Reference： [1]Molecules,2020,vol. 25
[2]Patent: WO2016/38061,2016,A1 .Location in patent: Page/Page column 23
[3]Patent: US2005/143588,2005,A1 .Location in patent: Page/Page column 5
[4]Tetrahedron Letters,2012,vol. 53,p. 6697 - 6700,4
[5]Tetrahedron,2005,vol. 61,p. 3013 - 3017
[6]Patent: CN105777693,2016,A .Location in patent: Paragraph 0055; 0056
[7]Patent: US2005/143588,2005,A1 .Location in patent: Page/Page column 5
[8]European Journal of Medicinal Chemistry,2016,vol. 112,p. 196 - 208
[9]Journal of cardiovascular pharmacology,2002,vol. 40,p. 399 - 410
[10]Justus Liebigs Annalen der Chemie,1931,vol. 489,p. 118,127, 140
[11]Chemische Berichte,1957,vol. 90,p. 2940,2943
[12]Journal Of Scientific and Industrial Research,1958,vol. 17 B,p. 266
[13]Journal of Chemical Crystallography,2005,vol. 35,p. 923 - 929
[14]Journal of Physical Chemistry B,2010,vol. 114,p. 13904 - 13910
[15]Chemical Communications,2017,vol. 53,p. 10180 - 10183

2
[ 1157-39-7 ]
[ 486-66-8 ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 4408 - 4410
[2]Chemistry - A European Journal,2019,vol. 25,p. 6907 - 6910
[3]Journal of Chemical Research,2008,p. 683 - 685
[4]Journal of the Chemical Society,1933,p. 274

3
[ 17720-60-4 ]
[ 122-51-0 ]
[ 486-66-8 ]

Reference： [1]Journal of Chemical Research,2008,p. 683 - 685
[2]Tetrahedron Letters,2012,vol. 53,p. 6697 - 6700,4
[3]Chemische Berichte,1959,vol. 92,p. 819

4
[ 290-87-9 ]
[ 17720-60-4 ]
[ 486-66-8 ]

Reference： [1]Angewandte Chemie,1981,vol. 93,p. 129 - 130

5
[ 17720-60-4 ]
[ 486-66-8 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1991,p. 3005 - 3008
[2]Proceedings of the Iowa Academy of Science,1954,vol. 61,p. 271,275

6
[ 17720-60-4 ]
[ 4637-24-5 ]
[ 486-66-8 ]

Reference： [1]Journal of Agricultural and Food Chemistry,1994,vol. 42,p. 1869 - 1871

7
[ 486-66-8 ]
[ 17238-05-0 ]

Yield	Reaction Conditions	Operation in experiment
48%	With palladium 10% on activated carbon; ammonium formate; In methanol; at 50℃; for 4h;Inert atmosphere;	200 <strong>[486-66-8]Daidzein</strong> 1.27 g (5.0 mmol) was put into four mL(s) mouth round bottom flask, and, subsequently argon substitution was carried out. The ammonium formate 1.58g (25.0 mmol) and 10 wt% palladium carbon 113.5 mg (0.11 mmol) were added to the place which has added and stirred methanol 75 mL (15 L/mol) to this. It heated at 50 degrees C with the oil bath, and stirred for 4 hours. Then, it filtered keeping a solution at 45 degrees C or more, and removed the catalyst. 1.39 g (77 wt%, 84% of yield) The obtained solution was condensed and the rough product was obtained. Column chromatography (benzene/acetone = 4/1 - 2/1) refined this. Subsequently, it was made to recrystallize with methanol and dihydro<strong>[486-66-8]daidzein</strong> of 612 mg was obtained (48% of yield).
	With hydrogen; potassium hydroxide;palladium/alumina; In ethanol; under 375.038 Torr;	Hydrogenation of <strong>[486-66-8]daidzein</strong> in ethanol and 1 M potassium hydroxide solution with 10% Palladium on alumina catalyst and a hydrogen pressure of 0.5 bar in a stainless steel reactor. After the completion of the hydrogenation process the material was filtered and charged into a glass lined mild steel reactor where the pH was adjusted to 6.96 with 1 M acetic acid. The resulting slurry was diluted further with water and then filtered to provide compound 35. The product was dried in vacuum oven at 60 C.

Reference： [1]Journal of Organic Chemistry,1997,vol. 62,p. 7690 - 7693
[2]Patent: JP2015/44770,2015,A .Location in patent: Paragraph 0076-0078
[3]Journal of Organic Chemistry,2003,vol. 68,p. 6864 - 6869
[4]Bioscience, Biotechnology and Biochemistry,2009,vol. 73,p. 1435 - 1438
[5]Chemical and Pharmaceutical Bulletin,2012,vol. 60,p. 513 - 520
[6]Patent: WO2012/61409,2012,A1 .Location in patent: Page/Page column 35; 37

8
[ 17720-60-4 ]
[ 68-12-2 ]
[ 486-66-8 ]

Reference： [1]Chemical Biology and Drug Design,2013,vol. 82,p. 317 - 325
[2]Chemistry and biodiversity,2015,vol. 12,p. 963 - 979
[3]Chemical and Pharmaceutical Bulletin,2009,vol. 57,p. 346 - 360
[4]Journal of the Chemical Society. Perkin transactions I,2000,vol. 4,p. 567 - 570
[5]Chemical and Pharmaceutical Bulletin,2012,vol. 60,p. 513 - 520

9
[ 17720-60-4 ]
zinc cyanide [ No CAS ]
[ 486-66-8 ]

Reference： [1]Chemische Berichte,1957,vol. 90,p. 2940,2943
[2]Chemistry of Heterocyclic Compounds,1992,vol. 28,p. 497 - 502
Khimiya Geterotsiklicheskikh Soedinenii, Sbornik,1992,p. 595 - 600

10
[ 17720-60-4 ]
[ 109-94-4 ]
sodium [ No CAS ]
[ 486-66-8 ]

Reference： [1]Chemische Berichte,1933,vol. 66,p. 686

11
[ 17720-60-4 ]
[ 68-12-2 ]
[ 486-66-8 ]
[ 148356-24-5 ]

Reference： [1]Synthetic Communications,2000,vol. 30,p. 469 - 484

12
[ 486-66-8 ]
[ 291759-05-2 ]

Yield	Reaction Conditions	Operation in experiment
60%		Adding 10 mg of <strong>[486-66-8]daidzein</strong> to the reaction vessel,200muL of heavy water,1mg Pt/C and 130muLdeuteriumSodium oxide solution,Filled with nitrogen and reacted at 130 C for 8 hours.Then, 130 muL of formic acid was added and reacted at 130 C for 1 hour.The reaction solution was collected and freeze-dried to obtain a solid.Dissolve the solid in ethanol,The filtrate was collected by filtration and dried to obtain a deuterated <strong>[486-66-8]daidzein</strong> solid.Mass spectrometry detectionsixDeuterated <strong>[486-66-8]daidzein</strong> (the main peak of the six major peaks),The mass spectrum and nuclear magnetic spectrum before and after the reaction are shown in Fig. 9.The structure is as follows,The yield was 60%.

Reference： [1]Patent: CN109879847,2019,A .Location in patent: Paragraph 0111-0113
[2]Journal of labelled compounds and radiopharmaceuticals,2000,vol. 43,p. 849 - 853
[3]Journal of labelled compounds and radiopharmaceuticals,2006,vol. 49,p. 973 - 978
[4]Journal of Organic Chemistry,2007,vol. 72,p. 5817 - 5819

13
[ 138286-76-7 ]
[ 486-66-8 ]
[ 371227-18-8 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 3320 - 3328

14
[ 2536-35-8 ]
[ 486-66-8 ]
16-[3-(4-hydroxy-phenyl)-4-oxo-4<i>H</i>-chromen-7-yloxy]-hexadecanoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 3320 - 3328

15
[ 56401-06-0 ]
[ 486-66-8 ]

Reference： [1]European Journal of Medicinal Chemistry,2003,vol. 38,p. 537 - 545

16
[ 486-66-8 ]
[ 142-61-0 ]
[ 602329-45-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	With dmap; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 4.5h;Cooling with ice;	General procedure: Flavonoid (1 (5.40 g, 0.02 mol), 2 (5.72 g, 0.02 mmol), 3 (5.45 g, 0.02 mmol), 4 (5.69 g, 0.02 mmol), 5 (5.08 g, 0.02 mmol), 6 (5.40 g, 0.02 mmol), or 7 (6.04 g, 0.02 mmol)) was dissolved in DMF (50 mL); Et3N (for 4, 5, 6.9 mL, 0.05 mol; for 1, 3, 6, 9.7 mL, 0.07 mol; for 2, 12.4 mL, 0.09 mol; for 7, 15.3 mL, 0.11 mol) and DMAP (240 mg, 2 mmol) were added. The mixture was then cooled in an ice-bath, and hexanoyl chloride (for 4, 5, 6.9 mL, 0.05 mol; for 1, 3, 6, 9.7 mL, 0.07 mol; for 2, 12.4 mL, 0.09 mol; for 7, 15.3 mL, 0.109 mol) was added and the reaction was allowed to slowly rise to room temperature in 30 min and stirred for an additional 4 h. After complete consumption of the flavonoid starting material as shown by TLC, the reaction mixture was diluted with CH2Cl2 (100 mL) and washed with 1 M HCl aqueous solution (100 mL), saturated aqueous NaHCO3 (100 mL * 2), brine (100 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure to afford the crude product (oil/solid), which was further purified by crystallization (methanol). Compound 1a-3a (1a, 9.8 g, 87%, Ref. [30]; 2a, 11.5 g, 85%; 3a, 10.4 g, 92%) were obtained as a light yellow solid and 4a-7a (4a, 8.4 g, 87%; 5a, 8.6 g, 95%, Ref. [28]; 6a, 9.1 g, 81%, Ref. [43]; 7a, 13.1 g, 83%) as a white solid. Analytical data and NMR spectra see Supporting Information.

Reference： [1]Tetrahedron Letters,2018,vol. 59,p. 4442 - 4447
[2]Journal of Organic Chemistry,2003,vol. 68,p. 6842 - 6845

17
[ 486-66-8 ]
[ 74-88-4 ]
[ 486-63-5 ]

Yield	Reaction Conditions	Operation in experiment
45.1%	With potassium carbonate; In dimethyl sulfoxide; at 20℃; for 2h;	To a solution of 5.1 g of <strong>[486-66-8]daidzein</strong> (20.06 mmol) in 40 ml of DMSO was added 3.5 g of anhydrous K2CO3 (25.4 mmol) and 6 ml of iodomethane (96.4 mmol). The mixture was stirred at room temperature for 2 hours and then poured into ice water to precipitate product. Precipitates were extracted with ethyl acetate, dried by flash evaporation and purified on a Sephadex LH-20 column (chloroform : methanol/7 : 3). Final product was recrystallized from acetone to give 2.3 g of crystalline analog 2, a yield of 45.1 % (w/w): mp 210-211 C ; 1H NMR (DMSO-d6) 6 3.89 (-OCH3), 6.81 (d, 2H, J= 8. 43 Hz, 3', 5'-H), 7.05 (dd, 1H, J= 8. 89,2. 39 Hz, 6-H), 7.11 (d, 1H, J= 2. 07 Hz, 8-H), 7.39 (d, 2H, J= 8.62 Hz, 2', 6'-H), 8.01 (d, 1H, J= 8. 87 Hz; 5-H), 8.35 (s, 1H, 2-H), 9.54 (s, 1H, 4'-OH). Anal. (Cl6Hl204) for C, H. Cacld : 71.64, 4.51 ; found: 71.24, 4.47.
27%	With potassium carbonate; 7-ethoxy-3-(4-hydroxyphenyl)-4H-chromen-4-one; In dimethyl sulfoxide; at 20℃; for 2h;	To synthesize 3-(4-Hydroxyphenyl)-7-methoxychromen-4-one (3a), 7-ethoxyl-4?-hydroxyisoflavone was added to asolution of <strong>[486-66-8]daidzein</strong> (1.27 g, 5 mmol) in 10 mE of DM50 was added anhydrous K2C03 (0.9 g, 6.5 mmol) and iodomethane (0.71 g, 5.0 mmol). The reaction mixture was stirred at room temperature for 2 h and then poured into icewatet The resulting mixture was extracted with ethyl acetate. The organic phases were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The residue was chromatographed over silica gel using hexanes/ethyl acetate (4:1) as eluent. The productwas recrystallized from acetone to provide 0.36 g of 3a as a white powder in 27% isolated yield.

Reference： [1]Journal of Agricultural and Food Chemistry,2008,vol. 56,p. 10376 - 10383
[2]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4069 - 4081
[3]Patent: WO2004/2470,2004,A1 .Location in patent: Page/Page column 22
[4]Journal of Medicinal Chemistry,2010,vol. 53,p. 6153 - 6163
[5]Patent: US9669004,2017,B2 .Location in patent: Page/Page column 6

18
[ 486-66-8 ]
[ 74-88-4 ]
[ 1157-39-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium carbonate; In acetone; for 8h;Reflux;	Typical procedure for the preparation of <strong>[486-66-8]Daidzein</strong> derivatives: A mixture of the corresponding isoflavone (1.34 mmol) and dry potassium carbonate (11.2 mmol) were taken in 100ml round bottom flask and dry acetone (50ml) was added. The reaction mixture was refluxed on water bath for 8 hours. Reaction mixture was filtered and filtrate was concentrated to remove acetone. Reaction was extracted with ethyl acetate (60ml) and washed with (50 x 3ml) of distilled water. Dried over sodium sulphate and concentrated to remove ethyl acetate. Chromatography was done on silica gel or neutral alumina using ethyl acetate, hexane or chloroform, hexane as solvent system to yield pure compounds.
35.2%		To a solution of 1.28 g of daidzin (5.0 mmol) in 40 ml of DMSO was added 3.84 g of NaOH pellets. The mixture was stirred at RT for 6 min and 3 ml of iodomethane (48.2 mmol) was added dropwise. The mixture was stirred at RT for another 6 min and poured into ice water. Product in the water was extracted with chloroform and dried. Residue was fractionated on a Sephadex LH-20 column (chloroform-methanol, 7: 3). Fractions that contained pure product were pooled, concentrated, and recrystallized from acetone to give 450 mg of analog 31 (crystalline needles), a yield of 35.2 (w/w): mp 162-163 C. 1H NMR (DMSO-d6) 8 3.79 (-OCH3), 3.90 (-OCH3), 6.99 (d, 2H, J= 8.36 Hz, 3', 5'-H), 7.07 (dd, IH, J= 8.88, 2.51 Hz, 6-H), 7.14 (d, 1H, J= 1.82 Hz, 8-H), 7.52 (d, 2H, J= 8. 67 Hz, 2', 6'-H), 8.02 (d, 1H, J= 8. 88 Hz, 5-H), 8.40 (s, 1H, 2-H). Anal. (Cl7Hl404) for C, H. Cacld : 72.33, 4.99 ; found :. 72.47, 4.95.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 677 - 681
[2]Chemical Communications,2015,vol. 51,p. 881 - 884
[3]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 4069 - 4081
[4]Patent: WO2004/2470,2004,A1 .Location in patent: Page/Page column 35
[5]Chemical and Pharmaceutical Bulletin,2006,vol. 54,p. 719 - 721

19
[ 485-72-3 ]
[ 897-46-1 ]
[ 37816-19-6 ]
[ 20575-57-9 ]
[ 486-66-8 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2004,vol. 52,p. 6623 - 6632

20
[ 486-66-8 ]
(+)-Equol [ No CAS ]
[ 531-95-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 1559 - 1567
[2]Patent: JP2015/44770,2015,A

21
[ 486-66-8 ]
[ 77-78-1 ]
[ 1157-39-7 ]

Reference： [1]Journal of Chemical Crystallography,2005,vol. 35,p. 923 - 929

22
[ 486-66-8 ]
[ 175205-63-7 ]
3-(4-hydroxyphenyl)-7-({5-[3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)chromen-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide In water; acetone for 72h; Heating / reflux;	5.B B. Alternative Preparation of a Compound of Formula I in which R1 is 3-(Trifluoromethyl)phenyl[1,2,4]oxadiazolyl, R2 is 4-Hydroxy, R3 is Hydrogen, X, Y and X are -CH-, V is Oxygen, and W is Methylene To a suspension of daidzein (2.0 g, 7.87 mmol) in acetone (80 ml) 2 N aqueous potassium hydroxide (3.94 ml, 7.87 mmol) was added, and the mixture was sonicated for a few minutes. To this mixture was added 3-chloromethyl-5-(3-trifluoromethylphenyl)-[1,2,4]oxadiazole (2.17 g, 8.26 mmol), and the reaction mixture was refluxed for 3 days. The mixture was concentrated under reduced pressure, and the residue dissolved in methanol, mixed with silica gel, and the solvent removed under reduced pressure. Purification by flash column chromatography, eluding with methylene chloride/methanol (95/5 to 90/10) provided pure 3-(4-hydroxyphenyl)-7-({5-[3-(trifluoromethyl)phenyl]-(1,2,4-oxadiazol-3 -yl)}methoxy)chromen-4-one as a white solid.
	With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 4.5h;	5.A A. Preparation of a Compound of Formula I in which R1 is 3-(Trifluoromethyl)-phenyl[1,2,4]oxadiazolyl, R2 is 4-Hydroxy, R3 is Hydrogen, X, Y and Z are -CH-, V is Oxygen, and W is Methylene A mixture of daidzein (100 mg, 0.4 mmol), 3-chloromethyl-5-(3-trifluoromethyl(phenyl[1,2,4]oxadiazole (108 mg, 0.41 mmol) and potassium carbonate (0.63 mg, 0.45 mmol) in anhydrous N,N-dimethylformamide (2 ml) was heated with stirring under argon at 80° C. for 4.5 hours. After cooling to room temperature, the mixture was quenched with about 12 ml of water, and stirred for 30 minutes. The precipitate formed was filtered off, washed three times with water, and dried under vacuum to provide crude product (152 mg). Chromatography of the crude product on silica gel, eluding with 5% to 50% ethyl acetate/hexanes, provided pure 3-(4-hydroxyphenyl)-7-({5-[3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)chromen-4-one. 1H NMR (400 MHz, DMSO-d6) δ: 9.58 (s, 1H), 8.48-8.39 (m, 3H), 8.12 (d, 1H, J=8.0 Hz), 8.08 (d, 1H, J=8.8 Hz), 7.92 (t, 1H, J=8.8 Hz), 7.42-7.38 (m, 3H), 7.23 (d, 1H, J=9.2 Hz), 6.82 (d, 2H, J=8.8 Hz), 5.61 (s, 2H). LC/MS analysis: tR=21.98 min (linear gradient B 5%→90%), (ESI) m/z 481.5 (M+H)+.
	With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 4.5h; Inert atmosphere;	5.A A. Preparation of a Compound of Formula I in which R1 is 3-(Trifluoromethyl)- phenyiri,2,4"\|oxadiazolyl, R2 is 4-Hydroxy, R3 is Hydrogen, X, Y and Z are -CH-, V is Oxygen, and W is Methylene[0175] A mixture of daidzein (100 mg, 0.4 mmol), 3-chloromethyl-5-(3- trifluoromethyl(phenyl[l,2,4]oxadiazole (108 mg, 0.41 mmol) and potassium carbonate (0.63 mg, 0.45 mmol) in anhydrous N,N-dimethylformamide (2 ml) was heated with stirring under argon at 800C for 4.5 hours. After cooling to room temperature, the mixture was quenched with about 12 ml of water, and stirred for 30 minutes. The precipitate formed was filtered off, washed three times with water, and dried under vacuum to provide crude product (152 mg). Chromatography of the crude product on silica gel, eluting with 5% to 50% ethyl acetate/hexanes, provided pure 3-(4- hydroxyphenyl)-7-({5-[3-(trifluoromethyl)phenyi](l,2,4-oxadiazol-3- yl)} methoxy)chromen-4-one.1H NMR (400 MHz, DMSO-d6) δ: 9.58 (s, IH), 8.48-8.39 (m, 3H), 8.12 (d, IH, J = 8.0 Hz), 8.08 (d, IH, J = 8.8 Hz), 7.92 (t, IH, J = 8.8 Hz), 7.42-7.38 (m, 3H), 7.23 (d, IH, J = 9.2 Hz), 6.82 (d, 2H, J = 8.8 Hz), 5.61 (s, 2H). LC/MS analysis: tR = 21.98 min (linear gradient B 5% -» 90%), (ESI) m/z 481.5 (M + H)+.

Reference： [1]Current Patent Assignee: AMYGDALA NEUROSCIENCES INC - US2008/32995, 2008, A1 Location in patent: Page/Page column 25
[2]Current Patent Assignee: AMYGDALA NEUROSCIENCES INC - US2008/32995, 2008, A1 Location in patent: Page/Page column 25
[3]Current Patent Assignee: GILEAD SCIENCES INC; THE ENDOWMENT FOR RESEARCH IN HUMAN BIOLOGY INC - WO2009/94028, 2009, A1 Location in patent: Page/Page column 62-63

23
[ 1050239-46-7 ]
[ 486-66-8 ]
7-(2-{2-[3-fluoro-5-(trifluoromethyl)phenyl](1,3-oxazol-5-yl)}ethoxy)-3-(4-hydroxyphenyl)chromen-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With caesium carbonate; In dimethyl sulfoxide; at 20℃; for 15h;	Step 5 4',7-Dihydroxyisoflavone (31.3 mg, 0.123 mmol), 2-[5-fluoro-3-(trifluoromethyl)phenyl]-4-(3-iodopropyl)- 1,3-oxazole (48.9 mg, 0.123 mmol, 1.0 equiv.) and cesium carbonate (40.0 mg, 0.123 mmol, 1.0 equiv) were placed in a 25 mL flask. To the flask was added dimethylsulfoxide (3 mL) at room temperature to dissolve the starting materials, and the reaction mixture stirred room temperature for 15 hours. To the mixture were added water (30 mL) and the whole was extracted with ethyl acetate (30 mL*3). The combined organic layers were washed with brine (30 mL) and dried with sodium sulfate to give a crude mixture as colorless oil (64.2 mg). The crude mixture was purified by column-chromatography (SiO2=80 g, hexane/EtOAc=2:1 to 1:1) to give 7-(2-{2-[3-fluoro-5-(trifluoromethyl)phenyl](1,3-oxazol-5-yl)}ethoxy)-3-(4-hydroxyphenyl)chromen-4-one (49.1 mg, 0.0934 mmol, 76%) as colorless crystals. Similarly prepared was 7-(3-{2-[3-fluoro-5-(trifluoromethyl)phenyl](1,3-oxazol-4-yl)}propoxy)-3 -(4-hydroxyphenyl)chromen-4-one.
76%	With caesium carbonate; In dimethyl sulfoxide; at 20℃; for 15h;	Step 5[0224] 4',7-Dihydroxyisoflavone (31.3 mg, 0.123 mmol), 2-[5-fluoro-3- (trifluoromethyl)phenyl]-4-(3-iodopropyl)-l,3-oxazole (48.9 mg, 0.123 mmol, 1.0 equiv.) and cesium carbonate (40.0 mg, 0.123 mmol, 1.0 equiv) were placed in a 25 mL flask. To the flask was added dimethylsulfoxide (3 mL) at room temperature to dissolve the starting materials, and the reaction mixture stirred room temperature for 15 hours. To the mixture were added water (30 mL) and the whole was extracted with ethyl acetate (30 mL x 3). The combined organic layers were washed with brine (30 mL) and dried with sodium sulfate to give a crude mixture as colorless oil (64.2 mg). The crude mixture was purified by column-chromatography (Sitheta2 = 80 g, hexane/EtOAc = 2: 1 to 1 : 1) to give 7-(2-{2-[3-fluoro-5-(trifluoromethyl)phenyl](l,3- oxazol-5-yl)}ethoxy)-3-(4-hydroxyphenyl)chromen-4-one (49.1 mg, 0.0934 mmol, 76%) as colorless crystals.

Reference： [1]Patent: US2008/32995,2008,A1 .Location in patent: Page/Page column 33
[2]Patent: WO2009/94028,2009,A1 .Location in patent: Page/Page column 90

24
[ 1050239-70-7 ]
[ 486-66-8 ]
7-((1R)-1-{3-[5-fluoro-3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-5-yl)}ethoxy)-3-(4-hydroxyphenyl)chromen-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%		Step 4[0238] To a solution of triphenylphosphine (262 mg, 1 mmol) in anhydrous tetrahydrofuran (15 ml) at -78C was added dropwise 40% diethylazodicarboxylate (0.45 ml, 1 mmol) in toluene, and the mixture stirred for 30 minutes at -78C. A solution of dihydroxyisoflavone (300 mg, 1.14 mmol) in a mixture of tetrahydrofuran (8 ml) and N,N-dimethylformamide (3 ml) was added slowly, and the mixture stirred for 10 minutes. A solution of (lS)-l-{3-[5-fluoro-3-(trifluoromethyl)phenyl](l,2,4- oxadiazol-5-yl)}ethan-l-ol (277 mg, 1 mmol) in tetrahydrofuran (8 ml) was added <n="99"/>dropwise, the mixture stirred at -78C for 3 hours, and then allowed to warm to room temperature, stirring for 36 hours.[0239] The reaction mixture was poured into ethyl acetate (40 ml), washed with water (10 ml), brine (2 x 10 ml), dried over sodium sulfate, and the solvent removed under reduced pressure. A mixture of dichloromethane/tetrahydrofuran (4 ml/1 ml) was added to the yellow residue, and the soluble portion was flash chromatographed over silica gel, eluting with ethyl acetate (0-30%)/hexane, to give a white solid, which was further purified by preparative thin layer chromatography, eluting with acetonitrile (2.5 97.5%/water, to provide 7-((lR)-l-{3-[5-fluoro-3-(trifluoromethyl)phenyl](l,2,4- oxadiazol-5-yl)}ethoxy)-3-(4-hydroxyphenyl)chromen-4-one; 245 mg, 0.48 mmol, 48%). MS mz 513.1 (M+H), anal HPLC > 99%, Chiralcel OJ-RH hplc 99.2% e.e. (mass detector), and 99.0% e.e. (UV detector) in acetonitrile/water.IH NMR (400 MHz; CDCl3) delta8.25 (d, 1 H, J = 9.0 Hz); 8.18 (s, IH); 7.99 (m, 1 H); 7.91 (s, IH); 7.49 (m, IH); 7.42 (d, 2 H, J = 8.6 Hz); 7.09 (dd, IH, J = 9.0, 2.3 Hz); 6.97 (d, IH, J = 2.3 Hz); 6.88 (d, 2H, J = 9.0 Hz); 5.59 (t, 1 H, J = 6.6 Hz); 1.96 (d, IH, J = 6.6 Hz).

Reference： [1]Patent: WO2009/94028,2009,A1 .Location in patent: Page/Page column 97-98
[2]Patent: US2008/32995,2008,A1 .Location in patent: Page/Page column 35

25
[ 486-66-8 ]
3-(2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With hydrazine hydrate; In ethanol; for 2h;Reflux;	General procedure: Compound 2 or 3 (1 mmol) and hydrazine hydrate (2 mmol) were refluxed in ethanol (15 mL) for about 2 h. All reactions were monitored by TLC until the 3-heteroarylchromones was fully consumed. After that the mixture was poured into ice water (100 mL) and was adjusted to pH 6=7 with 10% HCl. The white precipitate formed was filtered and purified via column chromatography on silica gel (dichloromethane) gave product 4 in 75%-94% yields and 5 in 91%-96% yields. 4a-4g were new compounds.

Reference： [1]Helvetica Chimica Acta,2007,vol. 90,p. 2096 - 2108
[2]Journal of Molecular Structure,2017,vol. 1149,p. 235 - 242

26
[ 15485-80-0 ]
[ 486-66-8 ]

Reference： [1]Journal Of Scientific and Industrial Research,1958,vol. 17 B,p. 266

27
[ 2528-00-9 ]
[ 486-66-8 ]
[ 640275-97-4 ]

Yield	Reaction Conditions	Operation in experiment
72.3%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 80℃; for 1.5h;	To a solution of 5.1 g of daidzein (20.08 mmol) in 60 ml of DMF was added 2.95 g of K2C03 (21. 38 mmol) and 5.0 g of ethyl5-(chloromethyl)-2-furancarboxylate (26.51 mmol) successively. The mixture was stirred and heated at 80 C for 1.5 hours and products were precipitated in 200 ml of ice water. Precipitates were collected by filtration and fractionated on a Sephadex-LH-20 column in chloroform : methanol (7: 3). Fractions that contained pure product were pooled, concentrated and recrystallized from acetone to give 5.89 g of analog 89. Analyses: white amorphous powder; yield, 72.3% ; mp 208-210 C. 1H NMR (DMSO-d6) 5 1.27 (-CH3), 4.28 (-CH2-O-), 5.34 (-O-CH2-), 6.81 (d, 2H, J= 8.7, 1.68 Hz, H-3', 5'), 6.87 (d, 1H, J= 3.2 Hz, H-8), 7.15 (dd, 1H, J= 8. 9,2. 7 Hz, H-6), 7.31 (d, 1H, J=7. 5 Hz, H-4"), 7.32 (d, 1H, J= 6. 8 Hz, H-3"), 7.40 (dd, 2H, J=8. 2,1. 8 Hz, H-2', 6'), 8.03 (d, 1H, J= 8. 9 Hz, H-5), 8. 38 (s, 1H, H-2), 9. 55 (s, 1H, OH-4'). 13C NMR (DMSO-d6) 5 14.1 (-CH3), 60.8 (-CH2-O-), 62.1 (-CH2-O-), 101.6 (C8), 113.1 (C-4"), 115.0 (C-6), 115.0 (C-3', 5'), 118.1 (C-10), 118.9 (C-3"), 122.3 (C-1'), 123.8 (C-3), 127.1 (C-5), 130.1 (C-2', 6'), 144.4 (C-2"), 153.2 (C-5"), 153.4 (C-2), 157.2 (C-9), 157.3 (C-4'), 157.8 (-C = 0), 161.9 (C-7), 174.8 (C-4). MS (m/z) 407.5 (M + H) +, 429.4 (M + Na) +, 445.4 (M + K) +. Elementary analyses (C23H1807) for C, H: Cacld. 67.98, 4.46 ; found 67.30, 4.62.

Reference： [1]Patent: WO2004/2470,2004,A1 .Location in patent: Page/Page column 44-45

28
[ 23468-31-7 ]
[ 486-66-8 ]
daidzein 7-(6"-chloropiperonyl) ether [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75.5%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 80℃; for 15h;	To a solution of 5.1 g of <strong>[486-66-8]daidzein</strong> (20.08 mmol) in 60 ml of DMF was added 2.7 g of K2CO3 (19.6 mmol) and 5.0 g of 6-chloropiperonylchloride (24.4 mmol) successively. The mixture was stirred and heated at 80 C for 15 hours and products were precipitated in 200 ml of ice water. Precipitates were collected by filtration and fractionated on a Sephadex-LH- 20 column in chloroform : methanol (7: 3). Fractions that contained pure product were pooled, concentrated and recrystallized from acetone to give 6.4 g of analog 87. Analyses: colorless crystals; yield, 75.5% ; mp 254-256 C. 1H NMR (DMSO-d6) No. 5. 18 (-O-CH2-), 6.10 (s, 2H,- O-CH2-O-), 6.81 (d, 2H, J= 8. 6,1. 6 Hz, H-3', 5'), 7.13 (dd, 1H, J= 8.9, 2.6 Hz, H-6), 7.16 (s, 1H, H-5"), 7.23 (s, 1H, H-2"), 7.27 (d, 1H, J= 2.0 Hz, H-8), 7.40 (d, 2H, J= 8. 7 Hz, H-2', 6'), 8.03 (d, 1H, J= 8. 9 Hz, H-5), 8.37 (s, 1H, H-2), 9.47 (s, 1H, 4'-OH- NMR (DMSO-d6) 8 67.7 (-CH2-O-), 101. 5 (C-8), 102.3 (-O-CH2-O-), 109. 8 (C-2"), 110.3 (C-5"), 115.0 (C-3', 5'), 115.0 (C-6), 117.9 (C-10), 122.3 (C-1'), 123.7 (C-3), 125.4 (C-1"), 127.0 (C-5), 130.0 (C-2', 6'), 146.7 (C-3"), 148.4 (C4"), 153.2 (C-2), 153.2 (C-2"), 157.2 (C-9), 157.3 (C-4'), 162.4 (C- 7), 174.4 (C-4). MS (m/z) 423.2 (M + H) +, 445. 3 (M + Na) +, 461.3 (M + K) +. Elementary analyses (C23Hl506Cl) : Cacld C, 65.34 ; H, 3.58. Found: C, 64.31 ; H, 3.61.

Reference： [1]Patent: WO2004/2470,2004,A1 .Location in patent: Page/Page column 43-44

29
[ 3389-21-7 ]
[ 486-66-8 ]
[ 640275-89-4 ]

Yield	Reaction Conditions	Operation in experiment
49%	With potassium carbonate In DMF (N,N-dimethyl-formamide) at 80℃; for 4h;	To a solution of 5.1 g of daidzein (20.08 mmol) in 60 ml of DMF was added 7.7 g of K2CO3 (55. 71mmol) and 5.0 g of 3- (2-bromoethyl) indole (22.31 mmol) successively. The mixture was stirred and heated at 80 °C for 4 hours and precipitated by pouring reaction mixture into 200 ml of ice water. Precipitates were collected by filtration and fractionated on a Sephadex-LH-20 column in chloroform : methanol (7: 3). Fractions that contained pure product were pooled, concentrated and recrystallized from acetone to give 2.5 g of analog 73. Analyses: white crystalline product; yield, 49%; mp 203-205 OC.'H NMR (DMSO-d6) 8 4.35 (t, 2H, -O-CH2-), 6.84 (d, 2H, J= 8. 7 Hz, H-3', 5'), 7.01 (dd, 1H, J= 7.4 Hz, H-7"), 7.05 (dd, 1H, J= 8.9, 2.6 Hz, H-6), 7.10 (dd, 1H, J= 8.2, 2.1, H5"), 7.29 (d, 1H, J= 1. 8 Hz, H-8), 7.38 (d, 1H, J= 8.0 Hz, H-4"), 7.41 (d, 2H, J= 8.7 Hz, H-2', 6'), 7.62 (d, 1H, J=7. 9 Hz, H-6"), 7.95 (s, 1H, H-2"), 8.01 (d, 1H, J=8. 9 Hz, H-5), 8.32 (s, 1H, H-2), 9.54 (s, 1H, OH-4'). 13C NMR (DMSO-d6) 8 24.7 (-CH2-), 68.9 (-CH2-O-), 101.0 (C-8), 110.2 (C-7"), 111.4 (C-5"), 114.9 (C-3', 5'), 115.0 (C-6), 117.6 (C-10), 118.4 (C-3"), 121.0 (C-8"), 122.4 (C-1'), 123.3 (C-4"), 123.7 (C-3), 127.3 (C-5), 130.1 (C-2', 6'), 136.2 (C-2"), 153.0 (C-2), 153.0 (C-9"), 157.3 (C-9); 157.4 (C-4'), 162.9 (C-7), 174.4 (C-4). MS (m/z) 397.9 (M) +. Elementary analyses (C25H, 904N) for C, H, N: Cacld. 75.55, 4. 82, 3.52 ; found 72.02, 5.60, 6.08.

Reference： [1]Current Patent Assignee: THE ENDOWMENT FOR RESEARCH IN HUMAN BIOLOGY INC - WO2004/2470, 2004, A1 Location in patent: Page/Page column 40

30
[ 14210-25-4 ]
[ 486-66-8 ]
[ 640275-94-1 ]

Yield	Reaction Conditions	Operation in experiment
86.3%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 80℃; for 4h;	To a solution of 5.1 g of <strong>[486-66-8]daidzein</strong> (20.08 mmol) in 60 ml of DMF was added 3.0 g of K2CO3 (21.74 mmol) and 3.6 g of 5-chloro-1-phenyl-lH-tetrazole (20.0 mmol) successively. The mixture was stirred and heated at 80 C for 4 hours and products were precipitated in 200 ml of ice water. Precipitates were collected by filtration and fractionated on a Sephadex-LH- 20 column in chloroform : methanol (7: 3). Fractions that contained pure product were pooled, concentrated and recrystallized from acetone to give 4.4 g of analog 86. Analyses: colorless crystals; yield, 86.3% ; mp 265-267 C. 1H NMR (DMSO-d6) 8 6.89 (d, 1H, J= 2.2 Hz, H-8), 6.96 (d, 2H, J= 8.8, 2.1 Hz, H-6), 7. 58 (dd, 2H, J=9. 31,1. 64Hz, H-6", 10"), 7.61 (d, 1H, J= 7.4Hz, H-8"), 7.67 (dd, 2H, J= 7. 8, H 7", 9"), 7.70 (dd, 2H, J= 8. 7,1. 6 Hz, H-3', 5'), 7.87 (d, 2H, J= 7. 83 Hz, H-2', 6'), 7.99 (d, 1H, J= 8. 8 Hz, H-5), 8.47 (s, 1H, H-2), 10.8 (s, 1H, OH-7). 3C NMR (DMSO-d6) 5 102.2 (C-8), 115.4 (C-6), 116.5 (C-10), 119.7 (C-1'), 122.5 (C-3), 123.2 (C-2', 6'), 127.3 (C-5), 129.9 (C-3', 5'), 129.9 (C-6", 10"), 130.4 (C-8"), 130.5 (C-7", 9"), 132.6 (C-11"), 152.9 (C-2), 154.1 (C-5"), 157.5 (C-9), 159.6 (C-4'), 162.8 (C-7), 174.3 (C-4). MS (m/z) 421.3 (M + Na) +, 437.2 (M + K) +, 397.2 (M-H)-. Elementary analyses (C22Hl404N4) for C, H, N. Cacld. 66.32, 3.54, 14.06 ; found 65.67, 3.62, 14.12.

Reference： [1]Patent: WO2004/2470,2004,A1 .Location in patent: Page/Page column 43

31
[ 486-66-8 ]
[ 73762-91-1 ]
[ 640275-93-0 ]

Yield	Reaction Conditions	Operation in experiment
98.4%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 80℃; for 14h;	To a solution of 5. 1 g of <strong>[486-66-8]daidzein</strong> (20.08 mmol) in 60 ml of DMF was added 3.0 g of K2C03 (21.7 mmol) and 5. 0 g of3-chloromethyl-2 (3H) -benzothiazolone (25.0 mmol) successively. The mixture was stirred and heated at 80 C for 14 hours and products were precipitated in 200 ml of ice water. Precipitates were collected by filtration and fractionated on a Sephadex-LH-20 column in chloroform : methanol (7: 3). Fractions that contained pure product were pooled, concentrated and recrystallized from acetone to give 5.02 g of analog 83. Analyses: colorless crystals; yield, 98.4% ; mp 234-235 OC.'H NMR (DMSO-d6) 5 6.1 (s, 2H,-O-CH2-), 6.82 (d, 2H, J= 8. 7,2. 5 Hz, H-3', 5'), 7.15 (dd, 1H, J= 8.9, 1.9 Hz, H-6), 7.27 (t, 1H, J= 7.34, 7.75 Hz, H-7"), 7.41 (d, 2H, J= 8.7 Hz, H-2', 6'), 7.42 (d, 1H, J= 8.8 Hz, H-4"), 7.43 (d, 1H, J= 2. 7 Hz, H-8), 7.50 (d, 1H, J=8. 2 Hz, H-5"), 7.70 (d, 1H, J= 7. 82 Hz, H-6"), 8.04 (d, 1H, J= 8.9 Hz, H-5), 8.39 (s, 1H, H-2). 13C NMR (DMSO-d6) 8 69.5 (-CH2- O-), 102.6 (C-8), 112.0 (C-1"), 115.0 (C-3', 5'), 115.3 (C-6), 118.6 (C-10), 121.1 (C-4"), 122.2 (C-1'), 123.1 (C-5"), 123.8 (C-3), 124.2 (C-6"), 126.9 (C-9"), 127.3 (C-5), 130.1 (C-2', 6'), 135.6 (C-8"), 153.3 (C-2), 157.0 (C-9), 157.3 (C-4'), 160.0 (C-7), 169.6 (-S-C=0), 174.4 (C- 4). MS (m/z) 440.4 (M + Na) +, 416.8 (M-H)-. Elementary analyses (C23HlsOsNS) for C, H, N, S: Cacld. 66.18, 3.62, 3.36, 7.68 ; found 65.80, 3.6, 3.42, 7.52.

Reference： [1]Patent: WO2004/2470,2004,A1 .Location in patent: Page/Page column 42-43

32
[ 486-66-8 ]
[ 5081-87-8 ]
[ 640275-90-7 ]

Yield	Reaction Conditions	Operation in experiment
12.9%	With potassium hydroxide; In water; acetone; at 20℃; for 48h;	To the suspension of daidzein (5.1g, 20.06 mmol) and 50 ml of acetone was added 30 ml of 2N aq. KOH (60.0 mmol) and 5. 0g of 3- (2-chloroethyl)-2, 4 (1H, 3X) quinazolinedione (22.26 mmol). The mixture was stirred at room temperature for 48h. Precipitates were filtered, dried and fractionated first on a silica gel column (chloroform-methanol, 9.25 : 0.75) followed by a Sephadex-LH-20 column (chloroform-methanol, 7: 3). Fractions containing pure product were pooled, concentrated and recrystallized from acetone to yield 617 mg HPLC-pure product. Analyses: white crystals; yield, 12.9% ; mp 270 C (decompose). 1HNMR (DMSO-d6) 5, 4.33-4. 38 (m, 4H,-N-CH2-CH2-O-), 6.82 (dd, 2H, J= 8.65, 3.2 Hz, 3', 5'-H), 7.03 (dd, 1H, J= 9.01, 2.44 Hz, 6-H), 7.18 (d, 1H, J= 7.27 Hz, 7"-H), 7.19 (d, 1H, 8-H), 7.21 (d, 1H, J= 7.72 Hz, 8"-H), 7.38 (d, 2H, J= 8. 55 Hz, 2', 6'-H), 7.66 (t, 1H, J= 7.43, 1.36, 9"-H), 7.94 (d, 1H, J= 7.75, 6"-H), 7.99 (d, 1H, J= 9.0 Hz, 5-H), 8.35 (s, 1H, 2- H). 9.58 (4'-OH). 13CNMR (DMSO-d6) ¢, 38.5 (-N-CH2-), 65.0 (-CH2-O-), 101.1 (C-8), 113.7 ( C-9"), 115.0 ( C-7"), 115.0 (C-3', 5'), 115.2 (C-6), 117.8 (C-10), 122.3 (C-5"), 122.6 (C-1'), 123.7 (C-3), 127.0 (C-6"), 127.4 (C-5), 130.1 (C-2', 6'), 135.1 (C-8"), 139.5 (C-10"), 150.1 (C-2"), 153.1 (C-2), 157.3 (C-9), 157.3 (C-4'), 162.1 (C-4"), 162.5 (C-7), 174.7 (C-4). Anal. (C25HlsO6N2) for C, H, N. Cacld, 67.87, 4.10, 6.33 ; found, 64.60, 4.13, 6.40.

Reference： [1]Patent: WO2004/2470,2004,A1 .Location in patent: Page/Page column 41

33
[ 486-66-8 ]
(+/-)-4-Hydroxy-Equol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With 5%-palladium/activated carbon; hydrogen; In N,N-dimethyl-formamide; at 25℃; under 600.06 Torr; for 3h;	Weigh 25.4 g (0.1 mol) of <strong>[486-66-8]daidzein</strong>, dissolve in 100 g of DMF, put 10 g of 5% palladium on carbon into a dry and clean hydrogenation kettle, and react at a temperature of 25 C, a hydrogen pressure of 0.08 MPa, and a rotation speed of 500 rpm for 3 hours. The reaction was completed, the catalyst was filtered, the filtrate was added to ice water, and a white solid was precipitated by stirring, filtered, washed with water, and dried to obtain 24 g of intermediate a with a yield of 93%;
	With hydrogen;10% Pd/Al2O3; In ethanol; under 750.075 Torr;	2. Hydrogenation; <strong>[486-66-8]Daidzein</strong> (3 g) was suspended in degassed ethanol (47.5 mL) and added to the hydrogenation vessel. Two further aliquots of degassed ethanol (47.5 mL each) were used to rinse the <strong>[486-66-8]daidzein</strong> remnants out of the transfer vessel into the hydrogenation vessel. The hydrogenation vessel was then purged with nitrogen by sequentially evacuating the air from the vessel to -100 Kpa, and recharging with nitrogen gas for a total of 5 cycles. Following this, the vessel was charged with hydrogen by sequentially evacuating the nitrogen from the vessel to -100 Kpa, and recharging with hydrogen gas again for a total of 5 cycles. HPLC was used to monitor the formation of the 4',7-dihydroxyisoflavan-4-ol reaction product until such time as no <strong>[486-66-8]daidzein</strong> or 4', 7-dihydroxyisoflavan-4-one (reaction intermediate) were observed. Figure 1 depicts the relative proportions of the reactants and products over time for the hydrogenation. At completion the reaction vessel was purged with nitrogen. This was carried out by evacuating the hydrogen from the vessel to - 100Kpa and recharging with nitrogen for a total of 5 cycles. The reaction mix was then filtered (celite/Whatman grade 114 paper combination) and the solid rinsed with fresh ethanol. The filtrate and rinsings were combined and then reduced in vacuo to one-third its original volume at 80C.

Reference： [1]Patent: CN110590727,2019,A .Location in patent: Paragraph 0027-0028; 0034-0036; 0041-0043; 0048-0050
[2]Patent: WO2005/103025,2005,A1 .Location in patent: Page/Page column 16

34
[ 552-66-9 ]
[ 486-66-8 ]

Yield	Reaction Conditions	Operation in experiment
	In hydrogenchloride;	D. Hydrolysis and Crystallization: 987.3 mg of <strong>[552-66-9]daidzin</strong> were refluxed in 470 ml 4N HCl for five hours at 105+-5 C. About 554.1 mg of daidzein was recovered by filtration which resulted in a 92% recovery. About 442.9 mg of this recovered daidzein from the hydrolysis step was dissolved in 200 ml methanol and crystallized in 30 ml methanol. About 339.0 mg daidzein crystal was obtained with 77% recovery and about 99% purity.

Reference： [1]Patent: US5679806,1997,A

35
malonylgenistin [ No CAS ]
[ 529-59-9 ]
[ 486-66-8 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In methanol; ethanol;	Example 8 To each of 1 g samples of daidzin and <strong>[529-59-9]genistin</strong> obtained in Example 7 were added 45 ml of methanol and 10 ml of 12N HCl, and the glycoside was decomposed under reflux for 6 hours. After cooling, the reaction mixture was diluted with water, and the solid product was collected by filtration, washed with water, dissolved in 90 ml of a 80% ethanol solution, filtered through a filter paper to give a supernatant. The supernatant was left standing at room temperature to deposit a crystalline product. The mixture was left standing overnight, and the crystals were collected and dried to give daidzein and genistein in the yields of 410 mg and 440 mg, respectively.

Reference： [1]Patent: US5789581,1998,A

36
[ 486-66-8 ]
[ 107-30-2 ]
[ 141330-20-3 ]

Yield	Reaction Conditions	Operation in experiment
91.78%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 8 - 40℃;	Example 1; Synthesis of the MOM-protected chromen-one (bis-MOM <strong>[486-66-8]Daidzein</strong>, 7-methoxymethoxy-3-(4'-methoxymethoxy-phenyl)-2H-chromen-4-one); A total of 329 g (1.29 mol) of 97% <strong>[486-66-8]daidzein</strong> (from LLC Laboratories) was mixed with 4.5 L of dichloromethane in a 12 L 4-neck round bottom flask equipped with a thermocouple, overhead stirrer, heating mantle, addition funnel and nitrogen line. The resulted white suspension was chilled to 8 C., and a total of 655.8 g (5.07 mol, 3.9 eq.) of diisopropylethylamine (DIEA) was added to the pot. After 20 min a total of 373 g (4.63 mol, 3.59 eq.) of chloromethylmethyl ether (MOM-Cl) was added to the mixture via an addition funnel at 8 C. An ice bath was removed, replaced with a heating mantle and allowed to warm up to room temperature within 2 hours. The pot temperature was maintained at 40 C. and reaction was kept (usually overnight) at this temperature until <strong>[486-66-8]daidzein</strong> and mono-MOM intermediate disappeared according to TLC (Rf=0.23 for <strong>[486-66-8]daidzein</strong>, 0.38 for mono-MOM and 0.62 for bis-MOM-<strong>[486-66-8]daidzein</strong> in EtOAc/hexane=1:1). The resulted clear brown solution was cooled to room temperature, and slowly poured under agitation on a cold mixture of 4 L of water, 1 kg of ice, 1 L of saturated sodium bicarbonate and 3 L of dichloromethane, which was prepared in a 20 L plastic bucket equipped with a powerful overhead stirrer and thermocouple. The pH of the resulted solution must stay basic during this work up to avoid degradation of the product. The organic phase was separated, and aqueous was back extracted with dichloromethane (2×1 L). The organic layers were combined, washed with water (2×3 L), sodium bicarbonate (3 L) and dried over sodium sulfate (500 g). The solvent was removed under reduced pressure to give 431 g (97% yield) of the product as a yellow solid. This material was purified by crystallization from 3.5 L of hot (56 C.) ethyl acetate followed by filtration and consequent washes with EtOAc/hexane=3:1 (2 L). Separated solid was dried overnight at 35 C. in a vacuum oven to yield 340.6 g (77% isolated yield) of bis-MOM-<strong>[486-66-8]daidzein</strong> as a white solid. A second crop (a total of 66.31 g of the product) was isolated from a mother liquor to give a bis-MOM-<strong>[486-66-8]daidzein</strong> in the 91.78% combined yield. Gas Chromatography Mass Spectrometry (GC-MS) traces and spectra were obtained on the bis-MOM <strong>[486-66-8]Daidzein</strong> product according to the GC-MS Method described in the Methods Section, and are shown in FIGS. 1A and 1B, respectively. Liquid Chromatography Mass Spectrometry (LC-MS) traces and spectra were obtained on the bis-MOM <strong>[486-66-8]Daidzein</strong> product according to the LC-MS Method described in the Methods Section, and are shown in FIGS. 1C and 1D, respectively. 1H NMR and 13C NMR data appear below. 1H NMR (300 MHz, CDCl3, delta): 8.21 (d, 1H, J=9.3 Hz), 7.92 (s, 1H), 7.48 (d, 2H, J=9.0 Hz), 7.07 (m, 4H), 5.26 (s, 2H, OCH2O), 5.20 (s, 2H, CH2O), 3.50 (s, 3H, CH3O), 3.48 (s, 3H, CH3O). 13C NMR (75 MHz, CDCl3, delta): 175.697, 161.337, 157.543, 152.228, 130.045, 127.716, 125.329, 124.690, 119.076, 116.147, 115.370, 102.969, 94.280, 56.290, 55.861.

Reference： [1]Patent: US2007/27329,2007,A1 .Location in patent: Page/Page column 8

37
[ 486-66-8 ]
[ 531-95-3 ]

Reference： [1]Bioscience, Biotechnology and Biochemistry,2008,vol. 72,p. 2660 - 2666
[2]Chemical and Pharmaceutical Bulletin,2009,vol. 57,p. 346 - 360

38
[ 1809-19-4 ]
[ 486-66-8 ]
[ 1022082-14-9 ]

Yield	Reaction Conditions	Operation in experiment
73%	With triethylamine; In tetrachloromethane; N,N-dimethyl-formamide; at 20℃;Cooling with ice;	General procedure: Synthesis of phosphorylated <strong>[486-66-8]daidzein</strong> derivatives was shown in Scheme 1. <strong>[486-66-8]Daidzein</strong> (0.6 g, 2.36 mmol) was added to a solution of NEt3 (0.8 mL) in DMF (6 mL) in a three-neck flask and the mixture was stirred until all the <strong>[486-66-8]daidzein</strong> was dissolved. The flask was put into an ice-water bath and then a solution of dialkyl phosphate (2.36 mmol) in CCl4 (6 mL) was added dropwise with vigorous stirring. After addition, the ice-water bath was removed and the reaction proceeded at room temperature for 24 h. The mixture was filtered and the filtrate was evaporated in vacuo. The residue was then dispersed in 30 mL water, filtered and further purified by column chromatography using chloroform-methanol (30:1, v/v) as eluent.

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2012,vol. 85,p. 298 - 302
[2]Phosphorus, Sulfur and Silicon and the Related Elements,2008,vol. 183,p. 527 - 537

39
[ 1809-20-7 ]
[ 486-66-8 ]
[ 1022082-13-8 ]

Yield	Reaction Conditions	Operation in experiment
82%	With triethylamine; In tetrachloromethane; N,N-dimethyl-formamide; at 20℃;Cooling with ice;	General procedure: Synthesis of phosphorylated <strong>[486-66-8]daidzein</strong> derivatives was shown in Scheme 1. <strong>[486-66-8]Daidzein</strong> (0.6 g, 2.36 mmol) was added to a solution of NEt3 (0.8 mL) in DMF (6 mL) in a three-neck flask and the mixture was stirred until all the <strong>[486-66-8]daidzein</strong> was dissolved. The flask was put into an ice-water bath and then a solution of dialkyl phosphate (2.36 mmol) in CCl4 (6 mL) was added dropwise with vigorous stirring. After addition, the ice-water bath was removed and the reaction proceeded at room temperature for 24 h. The mixture was filtered and the filtrate was evaporated in vacuo. The residue was then dispersed in 30 mL water, filtered and further purified by column chromatography using chloroform-methanol (30:1, v/v) as eluent.

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2012,vol. 85,p. 298 - 302
[2]Phosphorus, Sulfur and Silicon and the Related Elements,2008,vol. 183,p. 527 - 537

40
[ 486-66-8 ]
[ 1809-21-8 ]
[ 1022082-12-7 ]

Yield	Reaction Conditions	Operation in experiment
81%	With triethylamine; In tetrachloromethane; N,N-dimethyl-formamide; at 20℃;Cooling with ice;	General procedure: Synthesis of phosphorylated <strong>[486-66-8]daidzein</strong> derivatives was shown in Scheme 1. <strong>[486-66-8]Daidzein</strong> (0.6 g, 2.36 mmol) was added to a solution of NEt3 (0.8 mL) in DMF (6 mL) in a three-neck flask and the mixture was stirred until all the <strong>[486-66-8]daidzein</strong> was dissolved. The flask was put into an ice-water bath and then a solution of dialkyl phosphate (2.36 mmol) in CCl4 (6 mL) was added dropwise with vigorous stirring. After addition, the ice-water bath was removed and the reaction proceeded at room temperature for 24 h. The mixture was filtered and the filtrate was evaporated in vacuo. The residue was then dispersed in 30 mL water, filtered and further purified by column chromatography using chloroform-methanol (30:1, v/v) as eluent.

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2012,vol. 85,p. 298 - 302
[2]Phosphorus, Sulfur and Silicon and the Related Elements,2008,vol. 183,p. 527 - 537

41
[ 486-66-8 ]
[ 762-04-9 ]
[ 1022082-11-6 ]

Yield	Reaction Conditions	Operation in experiment
84%	With triethylamine; In tetrachloromethane; N,N-dimethyl-formamide; at 20℃;Cooling with ice;	General procedure: Synthesis of phosphorylated <strong>[486-66-8]daidzein</strong> derivatives was shown in Scheme 1. <strong>[486-66-8]Daidzein</strong> (0.6 g, 2.36 mmol) was added to a solution of NEt3 (0.8 mL) in DMF (6 mL) in a three-neck flask and the mixture was stirred until all the <strong>[486-66-8]daidzein</strong> was dissolved. The flask was put into an ice-water bath and then a solution of dialkyl phosphate (2.36 mmol) in CCl4 (6 mL) was added dropwise with vigorous stirring. After addition, the ice-water bath was removed and the reaction proceeded at room temperature for 24 h. The mixture was filtered and the filtrate was evaporated in vacuo. The residue was then dispersed in 30 mL water, filtered and further purified by column chromatography using chloroform-methanol (30:1, v/v) as eluent.

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2012,vol. 85,p. 298 - 302
[2]Phosphorus, Sulfur and Silicon and the Related Elements,2008,vol. 183,p. 527 - 537

42
[ 485-72-3 ]
[ 486-66-8 ]

Yield	Reaction Conditions	Operation in experiment
65%		Example 41 3-(4-Hydroxyphenyl)-7-hydroxy-4//-chromen-4-one (42) To a portion (100 mg) of 3-(4-methoxyphenyl)-7-hydroxy-4H-chromen-4-one(40b), dissolved in anhydrous dichloromethane (5 mL) and cooled to O0C, a 1 M solution of BBr3 in dichloromethane (1.5 mL) is dropped slowly; the solution is stirred at room temperature for 4 h and then is diluted with iced water. The pH is arranged to 6 with 5% Na2HPO4, the mixture is extracted with ethyl acetate, and the organic layer is separated and washed with brine, dried, and concentrated to yield, after crystallization from dichloromethane/methanol/ethyl acetate, 42 as off white colour solid (61 mg, 65% yield).

Reference： [1]Patent: WO2009/26657,2009,A1 .Location in patent: Page/Page column 38; 72
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 6835 - 6850

43
aqueous potassium hydroxide [ No CAS ]
[ 486-66-8 ]
[ 175205-63-7 ]
3-(4-hydroxyphenyl)-7-({5-[3-(trifluoromethyl)phenyl](1,2,4-oxadiazol-3-yl)}methoxy)chromen-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; hydrogen; acetone	5.B Preparation of a Compound of Formula I B. Alternative Preparation of a Compound of Formula I in which R1 is 3-(Trifluoromethyl)phenyl[1,2,4]oxadiazolyl R2 is 4-Hydroxy R3 is Hydrogen, X, Y and X are -CH-, V is Oxygen, and W is Methylene To a suspension of daidzein (2.0 g, 7.87 mmol) in acetone (80 ml) 2 N aqueous potassium hydroxide (3.94 ml, 7.87 mmol) was added, and the mixture was sonicated for a few minutes. To this mixture was added 3-chloromethyl-5-(3-trifluoromethylphenyl)-[1,2,4]oxadiazole (2.17 g, 8.26 mmol), and the reaction mixture was refluxed for 3 days. The mixture was concentrated under reduced pressure, and the residue dissolved in methanol, mixed with silica gel, and the solvent removed under reduced pressure. Purification by flash column chromatography, eluding with methylene chloride/methanol (95/5 to 90/10) provided pure 3-(4-hydroxyphenyl)-7-({5-[3-(trifluoromethyl)phenyl]-(1,2,4-oxadiazol-3-yl)}methoxy)chromen-4-one as a white solid.

Reference： [1]Current Patent Assignee: AMYGDALA NEUROSCIENCES INC - US2009/124672, 2009, A1

44
[ 1621-59-6 ]
[ 486-66-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	With aluminum (III) chloride; ethanethiol; In dichloromethane; at 0℃; for 0.5h;Inert atmosphere;	Ex. 7 Synthesis of 7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4-one (daidzein, Compound 6a)Under the protection of dry argon, a stirred solution of EtSH (20 mL) in CH2Cl2 (20 mL) was treated with AlCl3 (2 g, 15 mmol) at 0 C. After stirring for 5 min, the mixture was added with compound 5 as obtained in the above Example 6 (0.2 g, 0.56 mmol). After stirring at 0 C. for 30 min, the mixture was quenched with water (50 mL), and then warmed up to 40 C. to remove CH2Cl2 and EtSH. Thereafter, the mixture was extracted with EtOAc (10 mL×6). The organic layers were combined, washed with a saturated NaCl solution (10 m×2), and dried with anhydrous MgSO4. After filtration, the filtrate was concentrated in vacuo, followed by purification via silica gel column chromatography (ethyl acetate/n-hexane=1:6), thus giving the title compound 6a as a colorless crystal (0.13 g, 92% yield).Detected Properties of the Title Compound:M.p.: 329-330 C. (lit: 315-330 C.); Rf: 0.27 (ethyl acetate/n-hexane=1:1); IR (KBr) vmax: 3221, 1631, 1595, 1518, 1460, 1279, 1239, 1192, 843 cm-1; 1H-NMR (400 MHz, DMSO-4): delta 6.80 (d, J=8.8 Hz, 2H, H-3', H-5'), 6.86 (d, J=2.0 Hz, 1H, H-8), 6.93 (dd, J=8.8, 2.0 Hz, 1H, H-6), 7.38 (d, J=8.8 Hz, 2H, H-2', H-6'), 7.96 (d, J=8.8 Hz, 1H, H-5), 8.28 (s, 1H, H-2), 9.54 (br s, 1H, OH), 10.79 (br s, 1H, OH); 13C-NMR (100 MHz, DMSO-d6): delta 102.1, 114.9, 115.1, 116.6, 122.5, 123.5, 127.3, 130.1, 152.8, 157.2, 157.4, 162.5, 174.7; EIMS (70 eV) m/z (relative intensity, %): 254 (M+, 93), 253 (56), 137 (100), 118 (74), 89 (48), 63 (46), Anal calcd for C15H10O4: C 70.86, H 3.96; found: C 70.62, H 4.04.

Reference： [1]Tetrahedron Letters,2009,vol. 50,p. 2121 - 2123
[2]Patent: US2010/298581,2010,A1 .Location in patent: Page/Page column 8

45
[ 486-66-8 ]
[ 17238-05-0 ]
C₁₅H₁₂O₃ [ No CAS ]
[ 81267-65-4 ]
[ 531-95-3 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2009,vol. 57,p. 346 - 360

46
[ 486-66-8 ]
[ 74-88-4 ]
[ 485-72-3 ]
[ 1157-39-7 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2008,vol. 56,p. 10376 - 10383

47
[ 486-66-8 ]
[ 1208255-80-4 ]

Yield	Reaction Conditions	Operation in experiment
78%		To a solution of (S)-CBS-oxazaborolidin (0.1 eq) in THF (tetrahydrofurane), a solution of N-ethyl-N-isopropylanilin-borane (1 eq) in THF was added. To this mixture, a solution of <strong>[486-66-8]daidzein</strong> (1 eq) dissolved in THF was added slowly and dropwise at 25 within 1.5 hours. Subsequently, the reaction mixture was stirred for additional 10 minutes, quenched carefully with methanol and stirred for 30 minutes. The solvent was removed in a rotary evaporator and the product was purified by flash chromatography on a silica gel (230-400 mesh) with the eluant ethyl acetate/hex ane (4:1 v/v). The enantiomeric purity was determined by HPLC in a chiral column to 96% ee (25 cm Chiralcel OD-H chiral column; iso-PrOH/hexane: 1/99; flow rate: 0.3 ml/min; detection: 254 nm); the yield was 78% <strong>[486-66-8]daidzein</strong>-4-ol (2).

Reference： [1]Patent: WO2010/18199,2010,A1 .Location in patent: Page/Page column 10

48
[ 1740-74-5 ]
[ 486-66-8 ]
3-(4-hydroxyphenyl)-8,8-dimethyl-4H,8H-pyrano[2,3-f]chromen-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With 3-Methylpyridine; at 130℃; for 1h;Microwave irradiation;	A solution of <strong>[486-66-8]daidzein</strong> (0.25 g, 1.0 mmol) and 1, l-diethoxy-3-methyl-2-butene (0.20 g, 1.3 mmol) in 2 mL 3-picoline was irradiated at 130C for 1 hour under microwave. The solvent was evaporated under a vacuum and the residue was chromatographed over silica gel using hexanes as the eluant. Final product was recrystallized from acetone to give 0.13 g of 3 as colorless needle crystalline in 41% yield, m.p.: 262-264C (Dec). GC-MS: m/z 320 (M+), 305, 254, 187, 152, 118. 1H-NMR (DMSO-d6, 400 MHz): delta = 1.45 (s, 6H), 5.94 (d, J = 10.0 Hz, 1H), 6.79 (d, J = 10.0 Etazeta,IotaEta), 6.80 (d, J = 8.8Hz, 2H), 6.92 (d, J = 8.4 Hz, 1H), 7.38 (d, J = 8.8 Hz, 2H), 7.88 (d, J = 8.4 Hz, 1H), 8.36 (s, 1H), 9.57 (s, 1H, D20 exchangeable).
15%	With 3-Methylpyridine; (+)-Glyceollin I; In 5,5-dimethyl-1,3-cyclohexadiene; at 130℃; for 18h;	To synthesize 3-(4-Hydroxyphenyl)-8,8-dimethyl-8H- pyrano[2,3-fjchromen-4-one, (2) Glyceollin I was added to a solution of <strong>[486-66-8]daidzein</strong> (1.9 g, 7.2 mmol) in 360 mE of xylene was added 1,1-diethoxy-3-methyl-2-butene (2.4 g, 14.7 mmol) in 15 mE of xylene and 3-picoline (3.7 mmol in 43 mE xylene). The reaction mixture was refluxed at 130 C. for 18 hours. The solvent was evaporated under vacuum and the residue was chromatographed over silica gel using hexanes as eluent. Final product was recrystallized from acetone to give 0.34 g of 3-(4-Hydroxyphenyl)-8,8-dimethyl-8H- pyrano [2,3 -f]chromen-4-one as colorless needle crystalline, with an overall yield of 15%.

Reference： [1]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 143 - 148
[2]Patent: WO2014/165723,2014,A2 .Location in patent: Paragraph 0195
[3]Journal of Medicinal Chemistry,2010,vol. 53,p. 6153 - 6163
[4]Patent: US9669004,2017,B2 .Location in patent: Page/Page column 5; 6

49
[ 7200-25-1 ]
[ 486-66-8 ]
2-amino-5-[4-(2,4-dihydroxyphenyl)-5-(4-hydroxyphenyl)pyrimidin-2-ylamino]pentanoic acid [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,2010,vol. 47,p. 1209 - 1214

50
[ 17720-60-4 ]
[ 124-63-0 ]
[ 486-66-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 677 - 681

51
[ 486-66-8 ]
[ 106-89-8 ]
[ 1268612-83-4 ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium carbonate; In acetone; for 8h;Reflux;	Typical procedure for the preparation of <strong>[486-66-8]Daidzein</strong> derivatives: A mixture of the corresponding isoflavone (1.34 mmol) and dry potassium carbonate (11.2 mmol) were taken in 100ml round bottom flask and dry acetone (50ml) was added. The reaction mixture was refluxed on water bath for 8 hours. Reaction mixture was filtered and filtrate was concentrated to remove acetone. Reaction was extracted with ethyl acetate (60ml) and washed with (50 x 3ml) of distilled water. Dried over sodium sulphate and concentrated to remove ethyl acetate. Chromatography was done on silica gel or neutral alumina using ethyl acetate, hexane or chloroform, hexane as solvent system to yield pure compounds.
55%	In dimethyl sulfoxide; at 70℃;	<strong>[486-66-8]Daidzein</strong> (10 g, 0.0394 mol) was solved in 150 ml DMSO, NaOH(3.2 g, 0.08 mol) and epichlorohydrin (16 ml, 0.2 mol) were added into the solution. The solution was stirred overnight at 70C. The resulting solution was then poured into 1 M NaOH water solution.The precipitate was filtered and washed by 1 M NaOH till colorless eluate and dried in vacuum drying oven to obtain crude product.The crude product was separated on flash column to get compound 2a. Light yellow solid. Yield 55%. M.p. 117-118C. [a]D20 0 (c 0.5,CH2Cl2). 1H NMR (400 MHz, CDCl3) delta 8.15 (d, J 8.9 Hz, 1H), 7.85 (s,1H), 7.42 (t, J 5.8 Hz, 2H), 6.95 (dd, J 9.0, 2.4 Hz, 1H), 6.92 (d,J 8.8 Hz, 2H), 6.82 (d, J 2.3 Hz, 1H), 4.33e4.16 (m, 2H), 3.94 (td,J 11.1, 5.8 Hz, 2H), 3.37e3.28 (m, 2H), 2.87 (dt, J 15.0, 4.5 Hz, 2H),2.72 (ddd, J 10.6, 4.8, 2.6 Hz, 2H). 13C NMR (101 MHz, CDCl3)delta 175.78, 162.70, 158.49, 157.79, 152.21, 130.19, 127.97, 124.82,124.75, 118.79, 114.73, 114.68, 101.06, 69.31, 68.81, 50.15, 49.79,44.76, 44.58. Anal. Calcd. for C21H18O6: C 68.85, H 4.95; Found C68.81, H 4.96.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 677 - 681
[2]European Journal of Medicinal Chemistry,2013,vol. 64,p. 432 - 441

52
[ 578-86-9 ]
[ 486-66-8 ]

Reference： [1]Chemistry and Biology,2010,vol. 17,p. 392 - 401

53
[ 486-66-8 ]
[ 1450-93-7 ]
[ 1357294-54-2 ]

Reference： [1]Synthetic Communications,2011,vol. 41,p. 3590 - 3599

54
[ 1809-16-1 ]
[ 486-66-8 ]
[ 1352031-10-7 ]

Yield	Reaction Conditions	Operation in experiment
87%	With triethylamine; In tetrachloromethane; N,N-dimethyl-formamide; at 20℃;Cooling with ice;	General procedure: Synthesis of phosphorylated <strong>[486-66-8]daidzein</strong> derivatives was shown in Scheme 1. <strong>[486-66-8]Daidzein</strong> (0.6 g, 2.36 mmol) was added to a solution of NEt3 (0.8 mL) in DMF (6 mL) in a three-neck flask and the mixture was stirred until all the <strong>[486-66-8]daidzein</strong> was dissolved. The flask was put into an ice-water bath and then a solution of dialkyl phosphate (2.36 mmol) in CCl4 (6 mL) was added dropwise with vigorous stirring. After addition, the ice-water bath was removed and the reaction proceeded at room temperature for 24 h. The mixture was filtered and the filtrate was evaporated in vacuo. The residue was then dispersed in 30 mL water, filtered and further purified by column chromatography using chloroform-methanol (30:1, v/v) as eluent.

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2012,vol. 85,p. 298 - 302

55
[ 1809-17-2 ]
[ 486-66-8 ]
[ 1352031-09-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	With triethylamine; In tetrachloromethane; N,N-dimethyl-formamide; at 20℃;Cooling with ice;	General procedure: Synthesis of phosphorylated <strong>[486-66-8]daidzein</strong> derivatives was shown in Scheme 1. <strong>[486-66-8]Daidzein</strong> (0.6 g, 2.36 mmol) was added to a solution of NEt3 (0.8 mL) in DMF (6 mL) in a three-neck flask and the mixture was stirred until all the <strong>[486-66-8]daidzein</strong> was dissolved. The flask was put into an ice-water bath and then a solution of dialkyl phosphate (2.36 mmol) in CCl4 (6 mL) was added dropwise with vigorous stirring. After addition, the ice-water bath was removed and the reaction proceeded at room temperature for 24 h. The mixture was filtered and the filtrate was evaporated in vacuo. The residue was then dispersed in 30 mL water, filtered and further purified by column chromatography using chloroform-methanol (30:1, v/v) as eluent.

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2012,vol. 85,p. 298 - 302

56
[ 2283-25-2 ]
[ 486-66-8 ]
[ 1352031-08-3 ]

Yield	Reaction Conditions	Operation in experiment
78%	With triethylamine; In tetrachloromethane; N,N-dimethyl-formamide; at 20℃;Cooling with ice;	General procedure: Synthesis of phosphorylated <strong>[486-66-8]daidzein</strong> derivatives was shown in Scheme 1. <strong>[486-66-8]Daidzein</strong> (0.6 g, 2.36 mmol) was added to a solution of NEt3 (0.8 mL) in DMF (6 mL) in a three-neck flask and the mixture was stirred until all the <strong>[486-66-8]daidzein</strong> was dissolved. The flask was put into an ice-water bath and then a solution of dialkyl phosphate (2.36 mmol) in CCl4 (6 mL) was added dropwise with vigorous stirring. After addition, the ice-water bath was removed and the reaction proceeded at room temperature for 24 h. The mixture was filtered and the filtrate was evaporated in vacuo. The residue was then dispersed in 30 mL water, filtered and further purified by column chromatography using chloroform-methanol (30:1, v/v) as eluent.

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2012,vol. 85,p. 298 - 302

57
[ 486-66-8 ]
[ 360-97-4 ]
[ 1380484-14-9 ]

Reference： [1]Chinese Journal of Chemistry,2012,vol. 30,p. 997 - 1000

58
[ 531-95-3 ]
[ 486-66-8 ]

Yield	Reaction Conditions	Operation in experiment
		Due to the simultaneous synthesis of daidzein, it was not possible to determine the conversion rate thereof to <strong>[531-95-3]equol</strong>.

Reference： [1]Patent: US2013/231291,2013,A1 .Location in patent: Page/Page column

59
[ 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

60
[ 392-95-0 ]
[ 486-66-8 ]
7-(2,4-dinitro-6-(trifluoromethyl)phenoxy)-3-(4-hydroxyphenyl)-4H-chromen-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium tert-butylate; In N,N-dimethyl-formamide; at 20℃;	General procedure: The synthesis of flavone and isoflavone derivatives followed the general reaction pathway outlined in Scheme 1. The substituted dinitro-compounds (series A: 1 mmol; series B: 2 mmol) mixed with flavones or isoflavones (1 mmol) through by using t-BuOK (series A: 1 mmol; series B: 2 mmol) as catalyst in 20-30 ml DMF for 3-4 h at room temperature. The reaction was monitored by TLC. The products are extracted with ethyl acetate and saturated salt water, dried over Na2SO4, filtered and evaporated. The residue is purified by column chromatography using petroleum ether and ethyl acetate.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 70,p. 427 - 433

61
[ 29091-09-6 ]
[ 486-66-8 ]
7-(3-chloro-2,6-dinitro-4-(trifluoromethyl)phenoxy)-3-(4-(3-chloro-2,6-dinitro-4-(trifluoromethyl)phenoxy)phenyl)-4H-chromen-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium tert-butylate; In N,N-dimethyl-formamide; at 20℃;	General procedure: The synthesis of flavone and isoflavone derivatives followed the general reaction pathway outlined in Scheme 1. The substituted dinitro-compounds (series A: 1 mmol; series B: 2 mmol) mixed with flavones or isoflavones (1 mmol) through by using t-BuOK (series A: 1 mmol; series B: 2 mmol) as catalyst in 20-30 ml DMF for 3-4 h at room temperature. The reaction was monitored by TLC. The products are extracted with ethyl acetate and saturated salt water, dried over Na2SO4, filtered and evaporated. The residue is purified by column chromatography using petroleum ether and ethyl acetate.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 70,p. 427 - 433

62
[ 486-66-8 ]
[ 106-96-7 ]
[ 1449479-68-8 ]

Yield	Reaction Conditions	Operation in experiment
57%	With sodium hydride; In acetone; toluene; at 0 - 20℃;	To a solution of 500 mg (1.97 mmol) of <strong>[486-66-8]daidzein</strong> in 40 mL of anhydrous acetone at 0C, 60 mg (2.36 mol, 1.20 equiv.) of sodium hydride was added. When hydrogen gas evolution was stopped, 0.25 mL (2.32 mmol, 1.18 equiv) of 80%> propargyl bromide solution in toluene was added slowly into the reaction mixture. The reaction mixture was then allowed to warm up to room temperature. After the reaction completed, the reaction mixture was purified by flash column chromatography using ethyl acetate/hexanes as eluent affording 327 mg of 3-(4- hydroxyphenyl)-7-(prop-2-yn-l-yloxy)-4H-chromen-4-one (6) in 57% yield, m. p.: 228- 230C. GC-MS: m/z 292 (M+), 254, 207, 174, 145, 118. 1H-NMR (MeOD, 300 MHz): delta = 3.10 (d, J = 2.4 Hz, 1H), 4.93 (d, J = 2.4 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 7.12-7.18 (m, 2H), 7.40 (d, J = 8.7 Hz, 2H), 8.16 (d, J = 9.0 Hz, 1H), 8.22 (s, 1H). 13C-NMR (MeOD, 75 MHz): delta = 55.9, 76.5, 101.3, 114.8, 115.1, 126.8, 130.0, 136.4, 153.5.

Reference： [1]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 143 - 148
[2]Patent: WO2014/165723,2014,A2 .Location in patent: Paragraph 0193

63
[ 486-66-8 ]
[ 814-49-3 ]
[ 1266147-89-0 ]

Yield	Reaction Conditions	Operation in experiment
92%	With dmap; triethylamine; In tetrahydrofuran; at 70℃; for 3.5h;Cooling with ice; Inert atmosphere;	General procedure: Compound 1 (1.0mmol) was added to a solution of 20mL THF, DMAP (3.0mmol per OH group) and Et3N (3.0mmol per OH group), and the mixture was stirred until dissolved. A solution of ClP(O)(OEt)2 (4.0mmol per OH group) with 5mL THF was then added dropwise with vigorous stirring in an ice-water bath over 30min. After stirring at 70C for 3h under nitrogen, the reaction mixture was concentrated, diluted with EtOAc (3×30mL), washed with 0.5M HCl (3×15mL), 5% (w/v) NaOH (3×15mL) and brine, and dried over anhydrous Na2SO4. After removal of the solvent in vacuo, the residue was purified by column chromatography on deactivated silica gel with petroleum ether/EtOAc (1:1-1:4), CH2Cl2/MeOH (100:1-60:1) as eluant to give the corresponding product 2.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 74,p. 751 - 758

64
[ 3681-99-0 ]
[ 2280-44-6 ]
[ 486-66-8 ]

Reference： [1]Biological and Pharmaceutical Bulletin,2013,vol. 36,p. 635 - 640

65
[ 486-66-8 ]
[ 66998-80-9 ]
7-O-chloroacetyl daidzein [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With pyridine; In acetone; at 0 - 20℃; for 4h;	10.0 g <strong>[486-66-8]daidzein</strong> and 25 ml anhydrous pyridine were dissolved in 400 ml acetone to obtain a first mixed solution, and the first mixed solution was stirred mechanically and maintained at 0 C., and then added slowly with 27.3 chloroacetyl chloride dropwise, after completion of dropping, the first mixed solution was kept at 0 C. and continued to react for 2 h, and then warmed naturally to room temperature and continued to react for 2 h, and then the first mixed solution was sampled and detected by TLC (V (petroleum ether):V (ethyl acetate)=1:1), the result of detection indicated that the reaction was complete. The mixture after the reaction was filtered, and the filter cake was washed with water to make the pH value achieve pH=7.0, and then dried under vacuum to give 12.0 g 7-O-chloroacetyl <strong>[486-66-8]daidzein</strong>, with a yield of 93%.

Reference： [1]Patent: US2014/336247,2014,A1 .Location in patent: Paragraph 0048; 0049; 0050

66
[ 358-23-6 ]
[ 486-66-8 ]
4-oxo-3-[4-(trifluoromethylsulfonyloxy)phenyl]-4Hchromen-7-yl trifluoromethanesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With pyridine; at 20 - 40℃; for 0.666667h;	To a solution of 1 (0.5 g, 1.96 mmol) in CH2Cl2 (20 mL) wasadded py (0.6 mL, 7.86 mmol) and the resulting mixture wasstirred at r.t. To the solution was added Tf2O (0.8 mL, 4.72mmol) and the mixture was stirred at r.t. for 10 min. Subsequently,the mixture was stirred at 40 C for 30 min. After cooling,the mixture was concentrated in vacuo and the product wasisolated by rapid flash column chromatography (silica gel,heptane-EtOAc, 8:2).Yield: 0.90 g (90%); white solid; mp 182-184 C. IR (KBr): 3093,2918, 2849 (w), 1648 (s), 1614 (m), 1578, 1551, 1536, 1530 (w)cm-1. 1H NMR (300 MHz, CDCl3): delta = 7.61-7.70 (m, 3 H, ArH),7.80 (d, J = 2.3 Hz, 1 H, ArH), 7.90 (d, J = 2.2 Hz, 1 H, ArH), 7.92-8.00 (m, 2 H, ArH), 8.75 (s, 1 H, CH=). 13C NMR (75.4 MHz,CDCl3): delta = 112.5 (CH), 116.0 (q, JC-F = 320 Hz, CF3), 119.2 (CH),120.0 (q, JC-F = 320 Hz, CF3), 121.3 (CH), 122.0, 123.8 (C), 128.5,131.2 (CH), 132.1, 148.8, 151.8, 155.9 (C), 156.0 (CH), 174.0(CO). 19F NMR (282.4 MHz, CDCl3): delta = -72.53 (3 F, CF3), -72.74(3 F, CF3). GC-MS (EI, 70 eV): m/z (%) = 519 (23) [M + H]+, 518(100) [M]+, 454 (12). HRMS (EI, 70 eV): m/z [M]+ calcd forC17H8F6O8S2: 517.95593; found: 517.95651.
0.4 g	With dmap; In dichloromethane; at 20℃;	Step 1: <strong>[486-66-8]Daidzein</strong> (1.27 g, 0.005 mol) was dissolved in DCM (30 mL), then trifluoromethanesulfonic acid anhydride (3.2 g, 0.011 mol, d 1.677, 1.86 mL) and 4- dimethylaminopyridine (1.22 g, 0.01 mol) were added and the resulting mixture was stirred until the reaction was finished. The reaction was quenched with satd. sodium carbonate solution and extracted with ethyl acetate. The combined organic layer was dried over MgS04 and concentrated. The crude was purified by flash column to afford solid product (0.40 g). -NMR (CDC13, 300 MHz): 8.43 (d J = 8.7 Hz, 1H), 8.08 (s, 1H), 7.66 (d J = 8.7 Hz, 2H), 7.50 (m, 1H), 7.42-7.33 (m, 3H). "C-NMR (CDC13, 75 MHz): 174.5, 156.4, 153.7, 152.4, 149.6, 131.4, 130.8, 129.3, 124.5, 124.1, 121.7, 119.1, 118.8 (q,J = 319 Hz), 111.6. GC-MS: 518.1 (M+).
1.75 g	With pyridine; In dichloromethane; at 20℃; for 3h;	Trifluoromethanesulfonic anhydride (Tf2O) (2.2 eq) was added at room temperatureTo a solution of daidzin A-1 (1 g) and pyridine (5 eq) in dichloromethane (50 mL)After the addition, the mixture was stirred at room temperature for 3 hours,TLC detection reaction is complete, the water quenching,Dichloromethane extraction. The methylene chloride layer was washed with 1 N HCl, saturated sodium bicarbonate, brine, dried,Rotate to give 1.75 g of product as a pale yellow intermediate A-2 solid.

Reference： [1]Synlett,2015,vol. 26,p. 2527 - 2530
[2]Patent: WO2016/4166,2016,A1 .Location in patent: Paragraph 0049; 00103
[3]Patent: CN103980259,2017,B .Location in patent: Paragraph 0042; 0043; 0044; 0045

67
[ 486-66-8 ]
[ 147907-42-4 ]
N-((phenoxy)((3-(4-hydroxyphenyl)-4-oxo-4H-chromene-7-yl)oxy)phosphoryl)-L-phenylalanine methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84.9%	With potassium carbonate; In acetone; at 25℃;Microwave irradiation;	General procedure: A 250mL, three-necked flask was changed with compound 14 (0.296g, 1mmol), a solution of phosphoramidate 2a-d (2-5mmol) in acetone (60mL), anhydrous potassium carbonate (2-5mmol). The mixture was stirred at 25C (600W) under microwave irradiation for 4-5h (TLC). The solvent was removed under reduced pressure and the filtrate was concentrated to give a crude residue as an oil, which was purified by column chromatography on silica gel to afford the product 16a-e. 4.1.28 ((Phenoxy)(2-(4-hydroxyphenyl)-4-oxo-4H-chromene-7-yl)phosphoryl) phenylalanine methyl ester (18a) Yield 84.9%; Colorless oil. 1H NMR (400 MHz, DMSO-d6) delta 9.61 (s, 1H, 4'-OH), 8.45 (s, 1H, H-2), 8.07 (d, 1H, J = 8.0 Hz, H-5), 7.43 (d, 2H, J = 8.0 Hz, H-2', H-6'), 7.37 (t, 2H, J = 8.0 Hz, H-3", H-5"), 7.27 (s, 1H, Ph-H), 7.22-7.08 (m, 9H, Ph-H), 6.93-6.90 (m, 1H, Ph-H), 6.84 (d, 2H, J = 8.0 Hz, H-3', H-5'), 4.11-4.07 (m, 1H, -CH), 3.55 (s, 3H, -OCH3), 3.03-2.75 (m, 2H, -CH2). 13C NMR (100 MHz, DMSO-d6) delta 175.2, 172.9, 157.8, 156.6, 154.6, 154.2, 150.6, 137.2, 130.6, 130.6, 130.3, 130.3, 129.7, 129.7, 128.6, 128.6, 127.9, 126.9, 125.5, 124.4, 122.5, 121.2, 120.5, 120.4, 118.5, 115.5, 115.4, 109.0, 56.8, 52.36, 31.15. HRMS (ESI, m/z) for C31H25NO8P ([M - H]?) Calcd: 570.1318; Found: 570.1325.

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 112,p. 196 - 208

68
[ 486-66-8 ]
[ 541-41-3 ]
O,O'-bis(ethoxycarbonyl)daidzein [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With triethylamine; In 1,4-dioxane; at 20℃; for 24h;	Example 1 1 : 0,0'-bis(ethoxycarbonyl)<strong>[486-66-8]daidzein</strong> (2b) A mixture of <strong>[486-66-8]daidzein</strong> (5.08 g, 20 mmol), dry dioxane (70 ml), ethyl chloroformate (10 ml, 105 mmol) and triethylamine (15 ml, 108 mmol) was stirred at r.t. for 1 day. Water (800 ml) was added and the resulting suspension was stirred for 30 min. The precipitate was filtered off, washed with water and dried on air. The yield of Omicron,Omicron'- bis(ethoxycarbonyl)<strong>[486-66-8]daidzein</strong> (2b) - 7.66 g (19.2 mmol, 96%).

Reference： [1]Patent: WO2016/38061,2016,A1 .Location in patent: Page/Page column 29

69
[ 486-66-8 ]
[ 79-22-1 ]
O,O'-bis(methoxycarbonyl)daidzein [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine; In 1,4-dioxane; at 20℃; for 3h;	Example 12: 0,0'-bis(methoxycarbonyl)<strong>[486-66-8]daidzein</strong> (2f) To a stirred suspension of <strong>[486-66-8]daidzein</strong> (5.28 g, 20.78 mmol) in dry dioxane (120 ml), methyl chloroformate (10 ml, 129 mmol) was added. To the stirred mixture Et3N (18 ml, 129 mmol) was added dropwise with cooling on the water bath at 50-60C. After Et3N is added, the bath is removed and reaction mixture is stirred for additional 3 hr at room temperature. The precipitate is filtered off, washed with some dioxane, crystallized from AcOH, washed with plenty of water and dried to give 6.14 g (16.6 mmol, 80%) of desired product. (0149) In further experiments, protective groups -CO-O-ethyl, -CO-butyl or -CO-phenyl were also attached selectively to the 4'and 7'hydroxy groups of <strong>[486-66-8]daidzein</strong>.

Reference： [1]Patent: WO2016/38061,2016,A1 .Location in patent: Page/Page column 29; 30

70
[ 486-66-8 ]
[ 105-36-2 ]
[ 38588-55-5 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium iodide; potassium hydroxide; In acetone; at 20℃;	1, 100mg <strong>[486-66-8]daidzein</strong> is dissolved in 4.0mL of acetone. Successively add 0.43mL 1mol/L potassium hydroxide solution. 6.4mg potassium iodide and 65muL ethyl bromoacetate. The reaction mixture was stirred at room temperature. Then 1mol L hydrochloric acid solution / was added in 20mL of distilled water and then with ethyl acetate and saturated sodium chloride solution were extracted twice, each time 20mL, organic layers were combined, dried over anhydrous sodium sulfate and filtered, rotary evaporated to remove ethyl acetate. The resultant crude ester reconstituted with acetone, chloroform: methanol = 20: 1 (v: v) as the developing solvent, at room temperature, thin layer chromatography, to obtain the desired product ester 51mg, yield 91%.

Reference： [1]Patent: CN105669628,2016,A .Location in patent: Paragraph 0077; 0078; 0079

71
[ 486-66-8 ]
[ 105-36-2 ]
[ 40575-72-2 ]

Yield	Reaction Conditions	Operation in experiment
83.1%		In a 250 mL round bottom flask,Add 3.3 g (13 mmol) <strong>[486-66-8]daidzein</strong>,8.3 g (60 mmol) of dried anhydrous potassium carbonate,120 mL of anhydrous acetone,Stirred at room temperature for 45min,Pipette Pipette 5.6mL (34mmol) of ethyl bromoacetate was added dropwise to the reaction flask,Stirring at room temperature 15min,To completely dissolve it,After heating to reflux.The progress of the reaction was monitored by TLC (developing solvent: ethyl acetate: petroleum ether = 1: 1.8)Until <strong>[486-66-8]daidzein</strong> basic disappeared,Stop heatingContinue stirring until it is naturally cooled to room temperature;Then evaporated to dryness under reduced pressure acetone,The resulting solid was washed with distilled water until neutral,Remove potassium carbonate,Suction filtered to give a white solid;This white solid was added to 45mL 3M sodium hydroxide solution was stirred thoroughly washed,Filtered to give a pale yellow solid;The pale yellow solid was washed with water until neutral,A white solid was obtained,Dried at room temperature under vacuum,5.3 g of crude product was obtained,The crude product was recrystallized from absolute ethanol,Get white crystal plate 4.3g,The yield was 83.1%.
82.8%		In a 100 mL round bottom flask, Add 2.5g (10mmol) <strong>[486-66-8]daidzein</strong>, 5.5 g (40 mmol) of dry anhydrous potassium carbonate, 80 mL of anhydrous acetonitrile, Stir at room temperature for 30 min, removed with pipette 3.3 mL (20 mmol) of ethyl bromoacetate was added dropwise to the reaction flask, Room temperature stirring l0min,So that it is completely dissolved, After heating the reflux. TLC was carried out to examine the progress of the reaction (ethyl acetate: petroleum ether = 1: 2)Until the raw material soybean glycosides basically disappeared,Stop heating,Continue stirring until natural cooling to room temperature; then vacuum rotary distillation solvent acetonitrile,The resulting solid was washed with distilled water to neutral, Removing potassium carbonate,The white solid was collected by filtration into a 30 mL portion of 3M sodium hydroxide solution, Filtered to give a pale yellow solid which was washed with water until neutral, To give a white solid,Room temperature vacuum drying, To obtain crude product 4.3g, The crude product was recrystallized from absolute ethanol, 3.5547 g of white flaky crystals were obtained in a yield of 82.80%.
82%	With potassium carbonate; potassium iodide; In acetone; at 80℃; for 1h;Inert atmosphere;	taking 2.542g (10mmol) <strong>[486-66-8]Daidzein</strong> and 4.827g water-free K 2 CO 3 placed in 100 ml flask in three, then adding 0.166g (1mmol) as a catalyst the KI, by adding 75 ml of anhydrous acetone, stirring under room temperature for 60 min, then adding 8.3 ml (25mmol) bromo acetic acid ethyl ester, the N 2 in order to protect the environment 80 C constant temperature heating to reflux, TCL monitoring of the reaction process. After the reaction is finished, most of the acetone recovery spin vaporization, first the residue with water to neutral, then using 40mL2mol/L fully stirring the NaOH solution washing, filtering, finally water to neutral, the white solid obtained is the structure of formula (III) isoflavone derivatives 3.5g, yield is 82%.

Reference： [1]Patent: CN105963290,2016,A .Location in patent: Paragraph 0053; 0054; 0055
[2]Patent: CN105497009,2016,A .Location in patent: Paragraph 0042; 0043; 0044
[3]Patent: CN105616399,2016,A .Location in patent: Paragraph 0055; 0056

72
[ 156-38-7 ]
[ 108-46-3 ]
[ 486-66-8 ]

Yield	Reaction Conditions	Operation in experiment
60%		A, condensation reaction:Step 1: Check the reaction kettle, dry and anhydrous, 75kg of p-hydroxyphenylacetic acid, 75kg of resorcinol and 50kg of zinc chloride are added to the reaction kettle, the reactor is 200L enamel kettle, Heating the steam, the bottom of the material began to melt when the start of mixing, the kettle material after the whole solution, start the vacuum valve, control the vacuum at 0.08MPa or more, the temperature control at 140 , the reaction for 20 minutes, after the end of the reaction closed the vacuum valve;Step 2: Add 150L of dissolved water to the reaction. The reactor was cooled by cold water until the temperature in the autoclave reached below 30 . The crystals were stirred for 2 hours, dried in a centrifuge and the mother liquor was collected. Water washing and then into the centrifuge in the dry, get a condensate one, and collect the washing liquid;Step 3: The mother liquor and lotion are added to the reaction kettle, the steam in the interlayer is heated and the vacuum valve is started. The vacuum degree is controlled above 0.08MPa, the temperature is controlled at 140 , the reaction is carried out for 20 minutes, and the vacuum valve is closed after the reaction.Step 4: Add 150L of dissolved water to the reaction, and the reactor interlayer is cooled by cold water until the temperature inside the autoclave reaches below 30 C. The crystals are stirred for 2 hours, dried in a centrifuge and washed with 150 L of water. Into the centrifuge in the dry, get condensate two;Step 5: The condensate one and the condensate two are mixed to obtain a condensate which is dried at 100 C until the water content is 0.5% or less;B, cyclization reaction:Step 1: Check the reaction kettle, dry and anhydrous, DMF300L, 50kg of condensate, 54.5kg of triethyl orthoformate, 10kg of forest and 12kg of glacial acetic acid are added to the reaction kettle. The reactor is 500L enamel , The reaction of the reactor in the steam, the temperature control at 140 , reflux reaction 5 hours, the reactor connected to the fractionation tower, distillation reaction product ethanol recovery, distillation tower outlet temperature of 75 , first with the top of the first valve , With the amount of alcohol production and then gradually open the following valve;Step 2: After the reaction is completed, the temperature of the reactor is cooled to the temperature of the reactor to 50 or less, start the vacuum valve, keep the vacuum above 0.08MPa, and recover the dimethylformamide by distillation.Step 3: The reaction vessel was cooled to below 100 C, 240 L of ethanol dissolved in 80% volume was added, heated by steam, controlled at 140 C for 2 hours, then cooled to below 25 C, stirred for 2 hours , Into the centrifuge to dry, filter cake with 30L ethanol washing, into the centrifuge in the dry, filter cake and then washed with 100L dilute hydrochloric acid, into the centrifuge in the dry, filter cake and then wash with 300L water, put Into the centrifuge in the dry, was crude;Step 4: The crude product is dried at 93 C to a moisture content of 0.5% or less;C, refined:Step 1: Ethanol 800L was added to the reaction kettle, and the reactor was a 1000L glass-lined kettle. The dried crude product was 7 kg and the activated carbon was 2.5 kg. The autoclave was heated in a temperature range of 140C, Hour, material one;Step 2: the material in a vacuum of 0.06MPa above the conditions of the filter with the filter filter, the material two, filter with the bottom of the filter canvas double layer pad, the penultimate layer for the white cloth pad, the penultimate Layer for the canvas pad, the top layer for the canvas bag;Step three: the material two at 140 under the conditions of steam, steamed to the remaining material to 70L when the stop the steam, the material was cooled three;Step four: the material three into the centrifuge in the dry, filter cake washed with 10L water, then into the centrifuge in the dry, and then 10L water washing, drying after the material four;Step five: the material four at 93 under the conditions of drying to a moisture content of 0.5% or less, was fine

Reference： [1]Patent: CN105859673,2016,A .Location in patent: Paragraph 0033-0051

73
[ 486-66-8 ]
4-(4-(4-hydroxyphenyl)-1H-pyrazol-5-yl)benzene-1,3-diol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With hydrazine hydrate; In ethanol; at 90℃;	General procedure: Hydrazines hydrate (2mmol, 2.0 equal) was added to a solution of flavones (5mmol, 1.0 equal) or isoflavones (5 mmol, 1.0 equal) in EtOH (10 mL). The mixture was stirred for 8-12h at 90C and the solvent was then evaporated in vacuum. The residue was purified by silica gel column chromatography, eluting with a solution of 10%-30% MeOH in dichloromethane (Scheme S1), to yield yellow solid 6-9.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 1545 - 1549

74
[ 486-66-8 ]
[ 79074-45-6 ]
7-((3,5,6-trimethylpyrazin-2-yl)methoxy)-3-(4-((3,5,6-trimethylpyrazin-2-yl)methoxy)phenyl)-4H-chromen-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With potassium carbonate; In tetrahydrofuran; N,N-dimethyl-formamide; acetone; for 2h;Inert atmosphere;	TMP-Br (5.63 mmol) and <strong>[486-66-8]daidzein</strong> (1.97 mmol) were dissolved in dry DMF (30 mL), thenK2CO3 (10.87 mmol) was added in portions. The mixture was refluxed and kept at 75 C for 2 hunder a nitrogen atmosphere; the brown solution was filtered and concentrated under vacuum.The product was separated by flash chromatography with petroleum ether-acetone (10:1) as eluentand recrystallized from dichloromethane. White solid, m.p.: 185.4-186.9 C, yield 62%. 1H NMR(CDCl3) (ppm) delta 8.223 (d, J = 9 Hz, 1H), 7.94 (s, 1H), 7.51 (d, J = 8.5 Hz, 2H), 7.09 (dd, J = 8.9, 2.3 Hz,1H), 6.77 (d, J = 8.6 Hz, 2H), 5.27 (s, 2H), 5.21 (s, 2H), 2.62 (s, 3H), 2.61 (s, 3H), 2.56 (s, 6H), 2.55 (s, 6H);13C NMR (CDCl3) (ppm) delta 175.77, 162.80, 158.57, 157.77, 152.16, 151.83, 151.25, 149.98, 148.90, 148.68,145.70, 144.61, 130.16, 127.91, 124.84, 124.71, 118.75, 114.93, 114.88, 101.45, 70.38, 69.98, 21.76, 21.66,21.45, 21.44, 20.62. MS (ESI) m/z: [M + H]+ 523.2351, calcd. for C31H30N4O4 522.2267.
62%	With potassium carbonate; In N,N-dimethyl-formamide; at 75℃; for 2h;Inert atmosphere;	Weigh 0.50g <strong>[486-66-8]daidzein</strong> in a 100mL round bottom flask, put TMP-Br in a molar ratio of 1: 2, add an appropriate amount of anhydrous DMF to the reaction flask and stir to dissolve, then add an appropriate amount of K2CO3, under nitrogen protection, the reaction bottle was placed in an oil bath at 75 C and heated for 2h (TLC followed the reaction). After the reaction is complete, cool and filter. The filtrate was heated in a water bath at 55 C, and DMF was removed using a rotary evaporator. After reconstituting with dichloromethane, adding silica gel to mix samples, silica gel column separation and purification, eluent petroleum ether / acetone = 10: 1-3: 1 elution, improved color development of potassium bismuth iodide, TLC detection, The target compound was obtained as a white powder, namely compound CH-11.. M.p .: 185.4-186.9 , yield 62%.

Reference： [1]Molecules,2018,vol. 23
[2]Patent: CN110857295,2020,A .Location in patent: Paragraph 0126; 0127

75
[ 50-00-0 ]
[ 45597-00-0 ]
[ 486-66-8 ]
8-(((3R,5S)-3,5-dimethylmorpholino)methyl)-7-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one [ No CAS ]

Reference： [1]Journal of Enzyme Inhibition and Medicinal Chemistry,2018,vol. 33,p. 1545 - 1553

76
[ 15191-27-2 ]
[ 486-66-8 ]
C₂₇H₂₄N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82.15%	With dmap; formaldehyd; In 1,4-dioxane; at 101.1℃; for 3h;	General procedure: Compound B (1 mmol, 0.254 g) was dissolved in dioxane (15 ml), and genistein (1.2 mmol, 0.48 g) or its derivative compound 1 (1.2 mmol, 0.307 g) or compound 2 (1.2 mmol, 0.417 g) or compound 3 (1.2 mmol, 0.266 g) or compound 4 (1.2 mmol, 0.282 g),37% formaldehyde (0.06-0.065ml, 1.2mmol), DMAP (2.5mg, 0.02mmol), reflux at 101.1 C for 3h, after the reaction, the reaction solution was extracted with dichloromethane more than three times. The solution was concentrated under pressure, and then subjected to column chromatography with 200-300 mesh silica gel. The dichloromethane / methanol volume ratio of 30-50: 1 was used as the eluent. The eluate containing the target compound was collected and evaporated under reduced pressure Solvent and drying, the target products B-0 (0.375g, 82.15%), B-1 (0.332g, 63.34%), B-2 (0.385g, 62.67%), B-3 (0.290g, 59.17%) were obtained. ), B-4 (0.275 g, 55.37%).

Reference： [1]Patent: CN110804056,2020,A .Location in patent: Paragraph 0067; 0068; 0069

77
[ 50-00-0 ]
[ 486-66-8 ]
[ 485-35-8 ]
(1R,5S)-3-((7-hydroxy-3-(4-hydroxyphenyl)-4-oxo-4H-chromen-8-yl)methyl)-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With dmap; In 1,4-dioxane; at 101.1℃; for 3.0h;	General procedure: The flavonoids compound (A ~ E, 1.0 mmol) was dissolved in 1,4-dioxane (10 ml), followed by addition of (-)-<strong>[485-35-8]cytisine</strong> (1, 1.2 mmol) or its derivative compounds (2~5, 1.2 mmol), HCHO (2.0 mmol, 37 ~ 40%), DMAP (0.02 mmol, 2.5 mg), heated and reflux at 101.1 C for 3 h, and the completion of the reaction was detected by TLC. After the reaction was completed, the mixture was cooled to room temperature and then treated with CH2Cl2 (20 mL) and water (40 mL), and then extracted with CH2Cl2 (20 mL × 3). After that, it was washed with brine, dried over anhydrous dried over anhydrous Na2SO4, and concentrated in vacuum. The residue was purified by silica-gel column chromatography using dichloromethane/methyl alcohol as eluant to give desired products.

Reference： [1]Tetrahedron Letters,2020

78
[ 486-66-8 ]
[ 75187-63-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: potassium carbonate / acetone / 12 h / 60 °C 2.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 2.5 h / 0 °C 3.1: copper(I) bromide / N,N-dimethyl-formamide; methanol / 1 h 3.2: 2 h / 120 °C 4.1: aluminum (III) chloride; dimethylsulfide / dichloromethane / 6 h / 5 - 20 °C

Reference： [1]Current Patent Assignee: THE 940TH HOSPITAL OF PLA JOINT LOGISTICS SUPPORT FORCES - CN111574490, 2020, A

79
[ 486-66-8 ]
[ 2106-10-7 ]
daidzein 7-α-O-glucoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With α-glucosidase from sulfolobus solfataricus; In dimethyl sulfoxide; at 45℃; for 2h;pH 9.0;Enzymatic reaction;	General procedure: A mixture of donor sugar (1, 0.12mmol) and acceptor (0.1mmol) in Tris-HCl buffer (5mL; 0.2M; pH 9.0) containing 30% DMSO was treated with MalA-D416A (1mg), and the mixture was incubated for 2h at 45C. The flavonoid glucosides were purified on a C18 SEP PAK cartridge (Waters) to remove unreacted sugar, DMSO, proteins and salts. After the solvent was evaporated under reduced pressure, transfer products were isolated by flash silica gel chromatography by solvent gradient elution (ethyl acetate/methanol/water, 17:2:1 to 7:2:1). The structures of purified product were characterized by LC-MS, 1D (1H and 13C) and 2D (COSY, HSQC, HMBC, and NOESY) NMR spectra, successively. The isolation yield of each transfer product was calculated using the weight of the isolated product based on the subjected flavonoid as the substrate.

Reference： [1]Bioorganic Chemistry,2021,vol. 107

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	486-66-8	MDL No. :
Formula :	C₁₅H₁₀O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZQSIJRDFPHDXIC-UHFFFAOYSA-N
M.W :	254.24	Pubchem ID :	5281708
Synonyms :		Chemical Name :	7-Hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one

Num. heavy atoms :	19
Num. arom. heavy atoms :	16
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	71.97
TPSA :	70.67 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-6.1 cm/s

Log Po/w (iLOGP) :	1.77
Log Po/w (XLOGP3) :	2.47
Log Po/w (WLOGP) :	2.87
Log Po/w (MLOGP) :	1.08
Log Po/w (SILICOS-IT) :	3.02
Consensus Log Po/w :	2.24

[ CAS No. 486-66-8 ] {[proInfo.proName]}

Quality Control of [ 486-66-8 ]

Related Doc. of [ 486-66-8 ]

Product Details of [ 486-66-8 ]

Calculated chemistry of [ 486-66-8 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 486-66-8 ]

Application In Synthesis of [ 486-66-8 ]

[ 486-66-8 ] Synthesis Path-Upstream 1~6

[ 486-66-8 ] Synthesis Path-Downstream 1~79

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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

Log S (ESOL) :	-3.53
Solubility :	0.0751 mg/ml ; 0.000295 mol/l
Class :	Soluble
Log S (Ali) :	-3.6
Solubility :	0.0641 mg/ml ; 0.000252 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.98
Solubility :	0.00264 mg/ml ; 0.0000104 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.79

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

Precautionary Statements-General
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Prevention
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P280	Wear protective gloves/protective clothing/eye protection/face protection.
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P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
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Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
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P311	Call a POISON CENTER or doctor/physician.
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P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
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P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
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P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
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P411
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P413
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P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling