[ CAS No. 87199-18-6 ] {[proInfo.proName]}

Name: 87199-18-6|(3-Hydroxyphenyl)boronic acid|98%
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Quality Control of [ 87199-18-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 87199-18-6 ]

Product Details of [ 87199-18-6 ]

CAS No. :	87199-18-6	MDL No. :	MFCD01074603
Formula :	C₆H₇BO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WFWQWTPAPNEOFE-UHFFFAOYSA-N
M.W :	137.93	Pubchem ID :	2734359
Synonyms :	3-Hydroxybenzeneboronic acid

Calculated chemistry of [ 87199-18-6 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	3.0
Molar Refractivity :	38.29
TPSA :	60.69 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-6.81 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	0.47
Log Po/w (WLOGP) :	-0.93
Log Po/w (MLOGP) :	-0.36
Log Po/w (SILICOS-IT) :	-1.2
Consensus Log Po/w :	-0.4

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.37
Solubility :	5.89 mg/ml ; 0.0427 mol/l
Class :	Very soluble
Log S (Ali) :	-1.31
Solubility :	6.7 mg/ml ; 0.0486 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.68
Solubility :	28.6 mg/ml ; 0.207 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.59

Safety of [ 87199-18-6 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 87199-18-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 87199-18-6 ]
Downstream synthetic route of [ 87199-18-6 ]

[ 87199-18-6 ] Synthesis Path-Upstream 1~9

1
[ 87199-18-6 ]
[ 98-88-4 ]
[ 6949-73-1 ]

Reference： [1] ChemCatChem, 2016, vol. 8, # 20, p. 3207 - 3212

2
[ 121-43-7 ]
[ 591-20-8 ]
[ 87199-18-6 ]

Yield	Reaction Conditions	Operation in experiment
58%	With sec.-butyllithium In tetrahydrofuran	(vi) Preparation of 3-hydroxylphenyl boronic acid 3-Bromophenol (8.65 g, 50 mmol) in dry THF (150 mL) was treated with sodium hydride (60percent, 2.4 g, 60 mmol) at r.t. After 1 h, sec-butyllithium (1.3 M, 50 mL, 65 mmoL) was added dropwise to the reaction solution at -78° C. The reaction mixture was then allowed to stir at the same temperature for 30 min prior to addition of trimethyl borate (15 mL). After warming up to r.t. for 2 hrs, the reaction mixture was quenched with water (50 mL), and extracted with dichloromethane (2*100 mL). The combined organic phases were dried over MgSO₄ and evaporated to give the title compound as a white solid (4.0 g, 58 percent), which was used in the Suzuki coupling reactions without further purification.

Reference： [1] Patent: US2003/187022, 2003, A1,

3
[ 30418-59-8 ]
[ 87199-18-6 ]

Reference： [1] Journal of the American Chemical Society, 1932, vol. 54, p. 4415,4418
[2] Patent: US2007/209123, 2007, A1, . Location in patent: Page/Page column 7

4
[ 108-43-0 ]
[ 87199-18-6 ]

Reference： [1] Journal of the American Chemical Society, 2012, vol. 134, # 28, p. 11667 - 11673
[2] Organic Letters, 2012, vol. 14, # 18, p. 4814 - 4817,4

5
[ 13331-27-6 ]
[ 87199-18-6 ]

Reference： [1] Journal of the American Chemical Society, 1932, vol. 54, p. 4415,4418

6
[ 76-09-5 ]
[ 87199-18-6 ]
[ 214360-76-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	at 20℃; for 48 h;	To a 500 mL three-necked flask, 3-hydroxyphenylboronic acid (10.0 g, 72.46 mmol, 1.0 eq) and methylene chloride (300 mL) were added, and pinacol (10.0 g, 84.60 mmol, 1.2 eq) was added under stirring, followed by stirring at room temperature for 48 h. The reaction solution was poured into water (400 mL). The mixed solution was poured into a separatory funnel. The organic phase was separated and the aqueous phase was extracted twice with dichloromethane (400 mL). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The crude product was purified by column chromatography (200-300 mesh silica gel, methylene chloride/methanol mixed solvent at a volume ratio of 100/1 as eluent) to obtain 15.0 g of a white solid with a yield of 94percent and a purity of 97percent.

Reference： [1] Patent: CN107188901, 2017, A, . Location in patent: Paragraph 0035; 0036
[2] Organic Letters, 2010, vol. 12, # 23, p. 5474 - 5477

7
[ 87199-18-6 ]
[ 871231-45-7 ]

Reference： [1] Journal of the American Chemical Society, 2012, vol. 134, # 28, p. 11667 - 11673
[2] Organic Letters, 2012, vol. 14, # 18, p. 4814 - 4817,4

8
[ 585-76-2 ]
[ 87199-18-6 ]
[ 171047-01-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate In 1,4-dioxane; water at 95℃; Inert atmosphere	General procedure: The halo aryl (1.0 equiv) was dissolved in a mixture of water:dioxane (1:1). The boronic acid or ester(1.5 equiv) and potassium phosphate (5.0 equiv) were added. The solution was degassed byvacuum/argon cycles (10 times) before addition of PdCl2(PPh3)2 (10 molpercent) and further degassed (5times). The resulting mixture was stirred at 95 °C under argon atmosphere for 16-20 hours. Thereaction mixture was filtered through Celite and diluted with water (approx. 30 mL) before washingwith chloroform (3 x 30 mL). If not stated otherwise, the aqueous phase was concentrated underreduced pressure and applied to a C18 precolumn before purification on a 10g or 60 g C18 column witha gradient of acetonitrile in water (10-100percent) to yield the desired product.

Reference： [1] European Journal of Medicinal Chemistry, 2018, vol. 145, p. 634 - 648

9
[ 87199-18-6 ]
[ 1293915-42-0 ]

Reference： [1] Patent: WO2012/52753, 2012, A1,
[2] Patent: WO2013/136075, 2013, A1,

[ 87199-18-6 ] Synthesis Path-Downstream 1~88

1
[ 87199-18-6 ]
[ 90914-41-3 ]
[ 108-42-9 ]
3-(3-hydroxy-phenyl)-4-(3-chloro-phenylamino)-1H-pyrazolo[3,4-d]pyrimidine [ No CAS ]

Reference： [1]Organic Letters,2003,vol. 5,p. 3587 - 3590

2
[ 591-20-8 ]
[ 87199-18-6 ]
[ 612-76-0 ]

Reference： [1]Journal of Organic Chemistry,2014,vol. 79,p. 4104 - 4118
[2]Journal of Medicinal Chemistry,2004,vol. 47,p. 4998 - 5008

3
[ 22726-00-7 ]
[ 87199-18-6 ]
[ 681161-44-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 60℃; for 24h;	Water (10 ml), sodium carbonate (4.76 g) and tetrakistriphenylphosphine palladium (866 mg) were added in that order to a dimethoxyethane (50 ml) solution containing <strong>[22726-00-7]3-bromobenzamide</strong> (3.0 g) and (3-hydroxyphenyl)boronic acid (2.27 g), followed by stirring at 60C for 24 hours. The reaction solution was cooled, diluted with EtOAc, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: EtOAc) to obtain a pale yellow powder (2.74 g). Using the resulting compound and in the same manner as in Reference Example 1, the compound of Reference Example 28 was obtained.

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4998 - 5008
[2]Patent: EP1849773,2007,A1 .Location in patent: Page/Page column 28

4
[ 28229-69-8 ]
[ 87199-18-6 ]
3'-(2-hydoxyethyl)biphenyl-3-ol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4998 - 5008

5
[ 87199-18-6 ]
[ 106920-05-2 ]
[ 1004980-16-8 ]

Yield	Reaction Conditions	Operation in experiment
77%	With sodium carbonate In water; acetonitrile at 80℃; for 1h;	10.B3_2 Method B3_2 Synthesis of intermediate: 3-(5-chloro-8-isopropoxyquinolin-7-yl)phenol; 5-chloro-7-iodo-8-isopropoxyquinoline (500mg, 1.7mmol), (3- hydroxyphenyl)boronic acid (238mg, Ummol) and PdPCy3 (18mg, 0.028mmol) were dissolved/suspended in a mixture of acetonitrile/water (4ml: 1ml respectively) and sodium carbonate solution (2M, 5ml) added. The mixture was then heated to 80oC under N2 with stirring for 1 hour. TIc indicated complete consumption of starting iodo compound. The solvent was removed in vacuo, the residue dissolved/suspended in ethyl acetate and washed with water and brine. The organic phase was dried over anhydrous magnesium sulphate and concentrated in vacuo to yield essentially pure product (tic and nmr) (350mg, 77%). MS 314 (MH+); 1 H NMR (CDCI3), 400 MHz δ: 9.01 (bs, 1 H), 8.92 (d, 1H), 8.51 (d, 1H), 7.55 (s, 1 H), 7.47 (dd, 1H), 7.35 (t, 1 H), 7.32 (s, 1 H), 6.97-7.02 (m, 2H), 4.36 (sept, 1 H), 1.12 (d, 6H).

Reference： [1]Current Patent Assignee: FORUM PHARMACEUTICALS INC; CHRONOGEN - WO2008/14602, 2008, A1 Location in patent: Page/Page column 53

6
[ 934495-31-5 ]
[ 87199-18-6 ]
[ 1013098-88-8 ]

Yield	Reaction Conditions	Operation in experiment
79%	With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 0.166667h; Microwave irradiation;	1 Example 1. 2-Amino-8-cvclopentyl-6-(3-hvdroxyphenyl)-4-methylpyridof2.3-d\|pyrimidin-7(8/-/)-one (Compound 147); To a solution of 2-amino-6-bromo-8-cyclopentyl-4-methylpyrido[2,3-d]pyrimidin-7(8/-/)-one (100 mg, 0.31 mmol), 3-hydroxyphenylboronic acid ( 50 mg, 1.2 equiv), dichlorobis(triphenylphosphine)palladium(ll) (6.5 mg, 009 mmol), DMF (2 ml_) in a 10 mL microwave vial was added potassium carbonate (3 M, 0.8 mL). The solution was degassed with N2 for 10 min before being capped and heated in the microwave reactor for 10 min at 120 0C. Once complete, the reaction was diluted with 1 N NaOH (10 mL) and EtOAc (50 mL). The EtOAc layer was separatted, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude product was submitted for chromatography purification. The title compound was obtained in (82.1 mg, 79% yield). LRMS: 337 (M+H)+. 1H NMR (DMSO-cfe, 400 MHz): 9.37 (1 H, s), 7.87 (1 H, s), 7.19 (3H, m), 7.11 (1 H, s), 7.03 (1 H, d), 6.74- 6.71 (1 H, m), 6.04-5.99 (1 H, m), 2.55 (3H, s), 2.24-2.22 (2H, m), 2.02 (2H, m), 1.77-1.75 (2H, m), 1.60- 1.58 (2H, m).

Reference： [1]Current Patent Assignee: PFIZER INC - WO2008/32162, 2008, A1 Location in patent: Page/Page column 35

7
[ 101066-87-9 ]
[ 87199-18-6 ]
C₁₄H₈F₃NO [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5529 - 5532

8
[ 87199-18-6 ]
[ 209808-18-4 ]
[ 692246-40-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium carbonate In ethanol; water; toluene at 90℃; for 5h;	7 INTERMEDIATE 7: tert-butyl 4- [ {4- [ (DIETHYLAMINO) carbonyl] phenyl} (3- hydroxyphenyl) methylene] piperidine-1-carboxylate A solution of INTERMEDIATE 5 (4.08 g, 9.04 mmol), 3-hydroxyphenylboronic acid (1.97 g, 14.3 mmol) and aqueous 2N sodium carbonate (11.3 mL, 22.6 mmol) in a 1: 1 mixture of toluene/ethanol (200 mL) was degassed for 20 minutes. Palladium tetrakistriphenylphosphine (1.05 g, 0.909 mmol) was added and the reaction mixture was purged with nitrogen and heated to 90 °C. After 5 h, the reaction was cooled to room temperature and saturated aqueous ammonium chloride was added. The mixture was extracted with two portions of ethyl acetate and the combined organic extracts were dried (NA2SO4), filtered and concentrated. The residue was purified by flash chromatography eluting with 0% to 100% ethyl acetate in hexanes to yield INTERMEDIATE 7 as a white solid (4.24 g, 100%). 1H NMR (400MHZ, CDC13) 8 1.10 (t, J = 7.42 Hz, 3H), 1.20 (t, J = 7.03 Hz, 3H), 1.42 (s, 9H), 2.25-2. 33 (m, 4H), 3.23-3. 31 (m, 2H), 3.39-3. 46 (m, 4H), 3.46-3. 54 (m, 2H), 6.51 (dd, J = 2.15, 1.56 Hz, 1H), 6.57 (ddd, J = 7.62, 1.56, 0.98 Hz, 1H), 6.62 (ddd, J = 8.20, 2.54, 0.98 Hz, 1H), 7.06-7. 12 (m, 1H), 7.19 (d, J = 8.40 Hz, 2H), 7.29 (d, J = 8.40 Hz, 2H).
100%	With sodium carbonate In ethanol; water; toluene at 90℃; for 5h;	6 INTERMEDIATE 6: TERT-BUTYL 4- [ {4- [ (DIETHYLAMINO) CARBONYL] PHENYL} (3- hydroxyphenyl) methylene] PIPERIDINE-1-CARBOXYLATE To a flask containing INTERMEDIATE 5 (4.08 g, 9.04 mmol) was added toluene (100 ML), ethanol (100 mL), 3-hydroxyphenylboronic acid (1. 97 g, 14.3 MMOL), and aqueous 2N sodium carbonate (11. 3 mL, 22.6 MMOL). The solution was degassed for 20 minutes, then palladium tetrakistriphenylphosphine (1. 05 g, 0.909 mmol) was added. The reaction mixture was purged with nitrogen and heated to 90 °C. After 5 h, the reaction was cooled to rt and saturated aqueous ammonium chloride was added. The mixture was extracted with two portions of ethyl acetate and the combined organic extracts were dried (NA2SO4), filtered and concentrated. The residue was purified by flash chromatography, eluting 0% to 100% ethyl acetate in hexanes, to yield INTERMEDIATE 6 as a colourless solid (4.24 g, 100%).'H NMR (400MHZ, CDCL3) 6 1. 10 (t, J = 7.42 Hz, 3H), 1.20 (t, J = 7.03 Hz, 3H), 1.42 (s, 9H), 2.25-2. 33 (M, 4H), 3.23-3. 31 (M, 2H), 3.39-3. 46 (M, 4H), 3.46-3. 54 (M, 2H), 6.51 (dd, J = 2.15, 1. 56 Hz, 1H), 6.57 (ddd, J = 7.62, 1.56, 0.98 Hz, 1H), 6.62 (ddd, J = 8. 20, 2.54, 0.98 Hz, 1H), 7.06-7. 12 (M, 1H), 7.19 (d, J = 8.40 Hz, 2H), 7.29 (d, J = 8. 40 Hz, 2H).
100%	With sodium carbonate In ethanol; water; toluene at 20 - 90℃; for 5.33333h;	INTERMEDIATE 7: tert-butyl 4-[{4-[(DIETHYLAMINO) CARBONYL] PHENYL} (3- hydroxyphenyl) methylene] piperidine-I-carboxylate To a flask containing INTERMEDIATE 5 (4.08 g, 9.04 mmol) was added toluene (100 mL), ethanol (100 mL), 3-hydroxyphenylboronic acid (1.97 g, 14.3 MMOL), and aqueous 2N sodium carbonate (11. 3 mL, 22.6 MMOL). The solution was degassed for 20 minutes, then palladium tetrakistriphenylphosphine (1. 05 g, 0.909 mmol) was added. The reaction mixture was purged with nitrogen and heated to 90 °C. After 5 h, the reaction was cooled to rt and saturated aqueous ammonium chloride was added. The mixture was extracted with two portions of ethyl acetate and the combined organic extracts were dried (NA2SO4), filtered and concentrated. The residue was purified by flash chromatography, eluting 0% to 100% ethyl acetate in hexanes, to yield INTERMEDIATE 7 as a colourless solid (4.24 g, 100%). 1H NMR (400MHZ, CDCL3) No. 1.10 (t, J = 7.42 Hz, 3H), 1.20 (t, J = 7.03 Hz, 3H), 1.42 (s, 9H), 2.25-2. 33 (m, 4H), 3.23-3. 31 (m, 2H), 3.39-3. 46 (m, 4H), 3.46-3. 54 (m, 2H), 6.51 (dd, J = 2.15, 1.56 Hz, 1H), 6.57 (ddd, J = 7.62, 1.56, 0.98 Hz, 1H), 6.62 (ddd, J = 8. 20, 2.54, 0.98 Hz, 1H), 7.06-7. 12 (m, 1H), 7.19 (d, J = 8.40 Hz, 2H), 7.29 (d, J = 8. 40 Hz, 2H).

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2004/41784, 2004, A1 Location in patent: Page 65
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2004/101521, 2004, A1 Location in patent: Page 18; 33-34
[3]Current Patent Assignee: ASTRAZENECA PLC - WO2004/100952, 2004, A1 Location in patent: Page 40

9
[ 852204-22-9 ]
[ 87199-18-6 ]
[ 915215-37-1 ]

Yield	Reaction Conditions	Operation in experiment
69%	With potassium carbonate In ethanol; water; toluene at 70℃; for 1.5h;	42 [00137] Example 42. (3R, 4S)-4- (3, 3'-Dihydroxybiphenyl-4-yl)-3- [ (3S)-3- (4- fluorophenyl)-3-hydroxypropyl]-1-phenylazetidin-2-one [00138] Using Suzuki coupling methodology, 5-Bromo-2-{(2S,3R)-3-{(3S)-3-[tert- butyl (dimethyl) silyl] oxy}-3- (4-fluorophenyl) propyl]-4-oxo-1-phenylazetidin-2-yl} phenyl acetate (100 mg, 0.16 mmol) was combined with 3-hydroxyphenyl boronic acid (29 mg, 0.21 mmol) with deoxygenated toluene (3 mL) and deoxygenated ethanol (1 mL). 2.0 M aqueous potassium carbonate (0.31 mL, 0.31 mmol) was added and the vessel was purged with nitrogen. Tetrakis (triphenylphosphine) palladium (O) (9 mg, 0.008 mmol) was added and the vessel purged again. The reaction was heated to 70 °C for 1.5 h, cooled, diluted with water and extracted with ethyl acetate (2 x). The combined organic layers were washed with water, brine, dried over sodium sulfate, filtered, concentrated and purified by chromatography (40 g silica gel, 20% to 90% ethyl acetate-hexane) to afford 4-{(2S, 3R)- 3- [ (3S)-3- ( [tert-butyl (dimethyl) silyl] oxy}-3- (4-fluorophenyl) propyl]-4-oxo-1- phenylazetidin-2-yl}-3'-hydroxybiphenyl-3-yl acetate (70 mg, 69% yield) ) ; Rf 0.34 (1: 2 ethyl acetate-hexane) ; 1H NMR (300 MHz, Cl) Cl3) 6 7.34-7. 17 (m, lOH), 7.06-6. 90 (m, 5H), 6.79 (ddd, J= 8.1, 2.5, 0.8 Hz, 1H), 6.03 (br s, 1H), 4.67 (d, J = 2.3 Hz, 1H), 4.64 (t, J= 5.6 Hz, 1H), 3.26 (ddd, J= 4.8, 2.5, 2.4 Hz, 1H), 2.27 (s, 3H), 1. 94-1.73 (m, 4H), 0.84 (s, 9H), -0. 02 (s, 3H), -0. 19 (s, 3H) ppm; MS [M-OSi (CH3) 2C (CH3) 3] + 508.0
69%	With potassium carbonate In ethanol; water; toluene at 70℃; for 1.5h;	42 Using Suzuki coupling methodology, 5-Bromo-2- {(2S,3R)-3-[(3S)-3- [tert- butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-4-oxo-l-phenylazetidin-2- yl}phenyl acetate (100 mg, 0.16 mmol) was combined with 3-hydroxyphenyl boronic acid (29 mg, 0.21 mmol) with deoxygenated toluene (3 mL) and deoxygenated ethanol (1 mL). 2.0 M aqueous potassium carbonate (0.31 mL, 0.31 mmol) was added and the vessel was purged with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (9 mg, 0.008 mmol) was added and the vessel purged again. The reaction was heated to 70 °C for 1.5 h, cooled, diluted with water and extracted with ethyl acetate (2 x). The combined organic layers were washed with water, brine, dried over sodium sulfate, filtered, concentrated and purified by chromatography (40 g silica gel, 20% to 90% ethyl acetate-hexane) to afford 4-{(2S,3R)-3-[(3S)-3-[tert-butyl(dimethyl)silyl]oxy}- 3-(4-fluorophenyl)propyl]-4-oxo-l-phenylazetidin-2-yl}-3'-hydroxybiphenyl-3-yl acetate (70 mg, 69% yield) ); Rf 0.34 (1 :2 ethyl acetate-hexane); 1H NMR (300 MHz, CDCl3) δ 7.34-7.17 (m, 10H), 7.06-6.90 (m, 5H), 6.79 (ddd, J = 8.1, 2.5, 0.8 Hz, IH), 6.03 (br s, IH), 4.67 (d, J = 2.3 Hz, IH), 4.64 (t, J = 5.6 Hz, IH), 3.26 (ddd, J = 4.8, 2.5, 2.4 Hz, IH), 2.27 (s, 3H), 1.94-1.73 (m, 4H), 0.84 (s, 9H), -0.02 (s, 3H), -0.19 (s, 3H) ppm; MS [M-OSi(CH3) 2C(CH3) 3]+ 508.0

Reference： [1]Current Patent Assignee: IRONWOOD PHARMACEUTICALS INC - WO2005/47248, 2005, A1 Location in patent: Page/Page column 75
[2]Current Patent Assignee: MARTINEZ EDUARDO; KONINKLIJKE DSM N.V. - WO2006/124713, 2006, A2 Location in patent: Page/Page column 247

10
[ 832711-58-7 ]
[ 87199-18-6 ]
[ 832711-59-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium carbonate In 1,4-dioxane; water at 90℃; for 16h;	9.9B Step 9B: Preparation of 5-(3-hydroxyphenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-6-methyl-3-[N-(benzyloxycarbonyl)-1(R)-1,2,3,4-tetrahydroisoquinoline]methylpyrimidine-2,4(1H,3H)-dione 9b To compound 9a (3.3 g, 5.0 mmol) in dioxane/water (90/10 mL) was added 3-hydroxyphenylboronic acid (1. 38 g, 10 mmol) and NA2CO3 (3.18 g, 30 mmol). The mixture was deoxygenated with nitrogen for 15 min, tetrakis (triphenylphosphine) palladium (0) (0.58 g, 0.5 mmol) was added and the reaction mixture was heated at 90 °C for 16 hr. The reaction mixture was evaporated and partitioned between EtOAc and H20. The organic layer was washed with brine, dried over NA2S04, concentrated and purified by column chromatography on silica gel with ethyl acetate/hexanes 2/3 to 1/1 to afford compound 9b (3.12 g, 93%). MS (CI) NILZ 674.0 (MH+).

Reference： [1]Current Patent Assignee: NEUROCRINE BIOSCIENCES INC - WO2005/7164, 2005, A1 Location in patent: Page 47

11
[ 109-04-6 ]
[ 87199-18-6 ]
[ 98061-22-4 ]

Yield	Reaction Conditions	Operation in experiment
88%	With phosphate potassium salt In DMF (N,N-dimethyl-formamide) at 80℃; for 12.25h;	XV. E 3-Pyridin-2-yl-phenol [0284] In a vial, a mixture of potassium phosphate (1.28 g, 6 mmol), 2- bromo-pyridine (0.2 mL, 2 mmol), 3-hydroxy-phenylboronic acid (338 mg, 2.4 mmol) in DMF (4 mL) was purged with argon while stirring for 15 min. After Pd (PPh3) 4 (235 mg, 0.1 mmol) was added and the vial was sealed. The mixture was heated for 12 h at 80 °C and at room temp, the mixture was quenched with water (lmL). The mixture was extracted with dichloromethane once the pH was adjusted to 7-8 with 10 % HC1. The combined organic phase was concentrated. The residue in ethyl acetate (35 mL) was washed with brine (5 x 20 mL) and water (25 mL) then concentrated. Flash column chromatography provided the product (300 mg, 88 %). 1H NMR (acetone-d6). No. : 6.92 (ddd, 1H, J = 8.0, 2.5 & 0.9 Hz), 7.32 (m, 2H), 7.59 (ddd, 1H, J = 7. 8, 2.5 & 1.0 Hz), 7. 67 (dd, 1H, J = 2.3 & 1.9 Hz), 7. 88 (m, 2H), 8.49 (s, 1H, OH), 8.66 (ddd, 1H, J = 4.8, 1.7 &1. 0 Hz).
81%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In ethanol; water; toluene Reflux;
76.1%	With potassium phosphate; palladium diacetate In water; isopropyl alcohol for 6h; Reflux;	1 synthesis of 3-(2-pyridyl)phenol (4-C) synthesis of 3-(2-pyridyl)phenol (4-C) Sequentially 1. 66g (12mmol) 3- hydroxyphenyl boronic acid (4-A), L 58g (lOmmol) 2- bromopyridine (4-B), 5. 33g (25mmol) potassium phosphate, 45mg (0. 2mmol) palladium acetate, 50ml of isopropanol and 50ml of water were added to a 250ml three reaction flask was heated to reflux for 6 hours. Completion of the reaction, after removal of isopropanol by rotary evaporation plus 40ml X 3 and extracted with ethyl acetate, dried over anhydrous magnesium sulfate and filtered two hours, solvent removal, crystallization, and dried to give 1. 32g as a pale yellow solid, i.e. Compound 4 -C, content of 98. 6% (HPLC), yield 76.1%.

76.1%	With potassium phosphate; palladium diacetate In water; isopropyl alcohol at 80℃; for 6h;	1 Synthesis of 3-(2-pyridinyl)phenol (4-C) 3-hydroxyphenylboronic acid (formula 4-A, 20 mmol, 2.77 g), 2-bromopyridine (formula 4-B, 10 mmol, 1.58 g), potassium phosphate (30 mmol, 6.39 g), palladium acetate (0.2 mmol, 45 mg), isopropanol (50 ml) and water (50 ml) were added to a 250 ml, three-necked reaction flask successively, heated to 80° C. to react for 6 hours. When the reaction was finished, isopropanol was removed by rotary evaporation and ethyl acetate (40 ml×3) was added for extraction, then the obtained organic phase was dried, filtered, desolventized, crystallized and dried to obtain 1.32 g of pale yellow solid, i.e. compound 4-C, with the content of 98.6% (HPLC) and the yield of 76.1%.
65%	With 1,1',1'',1'''-benzene-1,2,4,5-tetrayltetrakis(methylene)tetrakis-(piperidin-4-ol); palladium diacetate; potassium carbonate In ethanol; water at 20℃;

Reference： [1]Current Patent Assignee: ENDORECHERCHE, INC. - WO2005/66194, 2005, A1 Location in patent: Page/Page column 165-166
[2]Zhang, Yi; Zhao, Yu; Luo, Yu; Xiao, Liuqing; Huang, Yuxing; Li, Xingrong; Peng, Qitao; Liu, Yizhen; Yang, Bo; Zhu, Caizhen; Zhou, Xuechang; Zhang, Junmin [Organic Letters, 2017, vol. 19, # 24, p. 6470 - 6473]
[3]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN103910670, 2016, B Location in patent: Paragraph 0052; 0054; 0055
[4]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - US2017/1961, 2017, A1 Location in patent: Paragraph 0026; 0027
[5]Nallasivam, Jothi L.; Fernandes, Rodney A. [European Journal of Organic Chemistry, 2015, vol. 2015, # 16, p. 3558 - 3567]

12
N-(5-bromo-pyridin-3-yl)-3-methoxy-4-methyl-benzamide [ No CAS ]
[ 87199-18-6 ]
N-[5-(3-hydroxy-phenyl)-pyridin-3-yl]-3-methoxy-4-methyl-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium hydrogencarbonate In water; N,N-dimethyl-formamide at 80℃; for 18h;	Preparation of N-[5-(3-hydroxy-phenyl)-pyridin-3-yl]-3-methoxy-4-methyl-benzamide 267; To a solution of N-(5-bromo-pyridin-3-yl)-3-methoxy-4-methyl-benzamide (482mg, 1.50mmol) in de-gassed DMF (8ml) under a Na atmosphere, 3-hydroxyphenyl boronic acid (414mg, 3.8mmol), NaHCO3 (504mg, 6.00mmol), de-gassed de-ionised water (4ml), triphenylphosphine (59mg, 0.22mmol) and palladium acetate (17mg, 0.073mmol) were added. Reaction was stirred at 80°C for 18 hours. Reaction was cooled and evaporated to dryness. Residue was dissolved in EtOAc (40ml) and washed with NaaCOs (30ml) and de-ionised water (30ml), dried over MgSO4, filtered and evaporated to dryness. Residue was purified by flash chromatography. Mixture was pre absorbed onto flash silica and eluted with 5% MeOH/DCM. Compound 267 was isolated in a 95% yield. LC-MS, m/z [MH]+ 335. Retention time, 1.89 minutes. Method B. 1H NMR (DMSO-c/e, 400MHz): 5 = 3.42 (s, 3H, CH3), 4.10 (s, 3H, CH3), 7.05 (d, 1H, Ar-H), 7.25 (s, 1H, Ar-H), 7.32 (d, 1H, Ar-H), 7.53 (t, 2H, Ar-H) 7.72 (s, 1H, Ar-H), 7.78 (d, 1H, Ar-H), 8.62 (s, 1H, Ar-H), 8.87 (s, 1H, Ar-H), 9.12 (s, 1H, Ar-H) 9.85 (s, 1H, OH), 10.65 (s, 1H, NH).

Reference： [1]Current Patent Assignee: VICHEM CHEMIE KFT - WO2006/10637, 2006, A2 Location in patent: Page/Page column 107

13
3-(5-bromo-pyridin-3-yl-carbamoyl)-2-methyl-phenyl-acetate [ No CAS ]
[ 87199-18-6 ]
3-hydroxy-N-[5-(3-hydroxy-phenyl)-pyridin-3-yl]-2-methyl-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium hydrogencarbonate In water; N,N-dimethyl-formamide at 80℃; for 18h;	Preparation of 3-hydroxy-N-[5-(3-hydroxy-phenyI)-pyridin-3-yl]-2-methyl-benzamide (269); To a solution of 3-(5-bromo-pyridin-3-yl carbamoyl)-2-methyl phenyl acetate (542mg, 1.55mmol) in de-gassed DMF (8ml) under a Na atmosphere, 3-hydroxyphenyl boronic acid (428mg, 3.10mmol), NaHCO3 (522mg, 6.20mmol), degassed de-ionised water (4ml), triphenylphosphine (61 mg, 0.23mmol) and palladium acetate (17mg, 0.08mmol) were added. Reaction was stirred at 80°C for 18 hours. Reaction was cooled and evaporated to dryness. Residue wasdissolved in EtOAc (40ml) and washed Na2CO3 (30ml) and de-ionised water(30ml), dried over MgSCXt, filtered and evaporated to dryness. Residue waspurified by flash chromatography. Mixture was pre absorbed onto flash silica andeluted with 10% MeOH/DCM. Compound 269 was isolated in a 75% yield.LC-MS, m/z [MH]+ 321. Retention time, 1.45 minutes. Method B.1H NMR (DMSO-c/e, 400MHz): 8 = 2.09 (s, 3H, CH3), 6.85 (d, 1H, Ar-H), 6.89 (d,2H, Ar-H), 6.98 (s, 1H, Ar-H), 7.04 (m, 2H, Ar-H), 7.24 (t, 1H, Ar-H), 8.32 (s, 1H,Ar-H), 8.45 (s, 1H, Ar-H), 8.75 (s, 1H, Ar-H), 9.51 (d, 1H, O-H), 9.53 (s, 1H, O-H),10.45(sf 1H, N-H).

Reference： [1]Current Patent Assignee: VICHEM CHEMIE KFT - WO2006/10637, 2006, A2 Location in patent: Page/Page column 109-110

14
(5-bromo-pyridin-3-yl)-(3-methoxy-benzyl)-methyl-amine [ No CAS ]
[ 87199-18-6 ]
3-{5-[(3-methoxy-benzyl)-methyl-amino]-pyridin-3-yl}-phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium hydrogencarbonate In water; N,N-dimethyl-formamide at 80℃; for 18h;	Preparation of 3-{5-[(3-methoxy-benzyl)-methyl-amino]-pyridin-3-yl}-phenol(261); To a solution of (5-bromo-pyridin-3-yl)-(3-methoxy-benyl)-methyl-amine (160mg, 0.52mmol) in de-gassed DMF (10ml) under a N2 atmosphere, 3-hydroxyphenyl boronic acid (144mg, 1.04mmol), NaHCO3 (175mg, 2.10mmol), de-gassed de-ionised water (5ml), triphenylphosphine (21 mg, 0.078mmol) and palladium acetate (6mg, 0.026mmol) were added. Reaction was stirred at 80°C for 18 hours. Reaction was cooled and evaporated to dryness. Residue was dissolved in EtOAc (40ml) and washed with Na2CO3 (30ml) and de-ionised water (30ml), dried over MgSO4) filtered and evaporated to dryness. Residue was purified by flash chromatography. Mixture was pre absorbed onto flash silica, loaded onto a 10g isolute flash Si cartridge and eluted using CombiFlash instrumentation, with a gradient of 0-100% EtOAc/petroleum ether 40/60 (v:v). Compound 261 was isolated in 75% yield.LC-MS, m/z [MH]+ 321. Retention time, 2.00 minutes. Method B.1H NMR (DMSO-c/6, 400MHz): 8 = 3.10 (s, 3H, N-CH3), 3.70 (s, 3H, O-CH3), 4.65(s, 2H, CH2), 6.79 (m, 4H, Ar-H), 6.98 (s, 1H, Ar-H), 7.01 (d, 1H, Ar-H), 7.13 (s,1H, Ar-H), 7.21 (m, 2H, Ar-H), 8.03 (s, 2H, Ar-H), 9.52 (s, 1H, OH).

Reference： [1]Current Patent Assignee: VICHEM CHEMIE KFT - WO2006/10637, 2006, A2 Location in patent: Page/Page column 112

15
[ 913369-88-7 ]
[ 87199-18-6 ]
(3R,4S)-4-[3-(benzyloxy)-3'-hydroxybiphenyl-4-yl]-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-1-phenylazetidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: (3R,4S)-4-[2-(benzyloxy)-4-bromophenyl]-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-1-phenylazetidin-2-one; 3-hydroxyphenylboronic acid In ethanol; toluene at 20℃; for 0.7h; Stage #2: With potassium carbonate In ethanol; toluene at 90℃; for 5.66667h;	7 A 500-mL three-necked round-bottom flask was charged with (3i?,45)-4-[2- (benzyloxy)-4-bromophenyl]-3-[(35)-3-(4-fluorophenyl)-3-hydroxypropyl]-l- phenylazetidin-2-one (21.7 g, 38.7 mmol) and 3-hydroxyphenylboronic acid (6.4 g, 46.4 mmol) followed by addition of degassed 4:1 toluene-ethanol (97.5 niL, 0.4 M). The mixture was stirred using a mechanical stirrer at room temperature while nitrogen gas was bubbled directly into the solution for 25 min to displace oxygen. The starting materials dissolved completely after 17 min, and to the tan solution was added degassed 2.0 M aqueous potassium carbonate (39.0 mL, 78.0 mmol) followed by addition of solid palladium(O) tetrakis(triphenylphosphine) (2.23 g, 1.93 mmol). Nitrogen gas was bubbled directly into the solution for an additional 10 min to displace oxygen. The solution turned a yellow color and the mixture was heated to 90 0C (during heating the reaction remains yellow). The reaction was stirred for 5.5 h at 90 °C, cooled to room temperature, poured into ice cold water (300 mL), extracted with 1:1 ethyl acetate-heptane (250 mL) and washed with brine (100 mL). The aqueous layers were back-extracted sequentially with 1:1 ethyl acetate-heptane (250 mL). The combined organic layers were charged with silica gel (2.25 g) and activated carbon (2.25 g) and stirred overnight. The solution was filtered through Celite, washed with 1:1 ethyl acetate-heptane (200 mL) and concentrated to give an orange oil (26.8 g). The oil was dissolved in dichloromethane (65 mL), charged with silica gel (25 g) and transferred to a pad of silica gel (125 g) packed with dichloromethane. The pad was first eluted with dichloromethane (200 mL), 20% ethyl acetate-hexane (1000 mL) to remove impurities and 40% ethyl acetate-hexane (1500 mL) to elute the desired material. The solvent was concentrate in vacuo to afford (3i-,45)-4-[3-(benzyloxy)-3'-hydroxybiphenyl-4-yl]-3-[(3)S)-3-(4-fluorophenyl)-3- EPO hydroxypropyl]-l-phenylazetidin-2-one (Fl) (20.1 g, 91% yield) as a light tan foam; R/ 0.31 (1:1 ethyl acetate-hexane); HPLC purity 97.5 A%; 1H NMR (300 MHz, CDCl3) δ 7.45-7.26 (m, 9H), 7.23-7.15 (m, 5H), 7.11-7.02 (m, 4H), 6.95 (t, J= 8.8 Hz, 2H), 6.86-6.82 (m, IH), 5.20 (d, J= 11.4 Hz, IH), 5.14 (d, J= 11.4 Hz, IH), 5.12 (d, J= 2.3 Hz, IH), 4.59-4.53 (m, IH), 3.13-3.08 (m, IH), 2.20 (d, J= 4.4 Hz, IH), 1.98-1.80 (m, 4H) ppm.

Reference： [1]Current Patent Assignee: IRONWOOD PHARMACEUTICALS INC - WO2006/122216, 2006, A2 Location in patent: Page/Page column 47-48

16
[ 863783-61-3 ]
[ 87199-18-6 ]
3-[4-(5,6-Dimethyl-[2,2']bipyridin-3-yloxy)-quinolin-6-yl]-phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate In water; N,N-dimethyl-formamide at 70℃; for 3h;	11 N,N-Dimethylformamide (1 ml) and a 2 M aqueous potassium carbonate solution (0.5 ml) were added to 3-(6-bromo-quinolin-4-yloxy)-5,6-dimethyl-[2,2']bipyridine (30 mg), tetrakistriphenylphosphine palladium (9 mg) and 3-hydroxyphenylboric acid (31 mg) under an argon atmosphere, and the mixture was stirred at 70°C for 3 hr. The reaction mixture was cooled to room temperature, water was added to the cooled mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then extracted with 1 N hydrochloric acid, and the aqueous layer was washed with ethyl acetate. The aqueous layer was rendered alkaline by the addition of potassium carbonate and was extracted with ethyl acetate. The ethyl acetate layer was washed with water and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography with a chloroform-acetone system to give the title compound (31 mg, yield 100%). 1H-NMR (CDCl3, 400 MHz): δ 2.33 (s, 3H), 2.61 (s, 3H), 6.40 (d, J = 5.1 Hz, 1H), 6.77 - 6.84 (m, 1H), 7.06 (ddd, J = 7.6, 4.9, 1.0 Hz, 1H), 7.18 - 7.34 (m, 4H), 7.55 (ddd, J = 7.8, 7.8, 2.0 Hz, 1H), 7.79 (ddd, J = 8.0, 1.0, 1.0 Hz, 1H), 7.93 (dd, J = 9.0, 2.2 Hz, 1H), 8.09 (d, J = 8.8 Hz, 1H), 8.42 - 8.47 (m, 1H), 8.53 (d, J = 5.4 Hz, 1H), 8.57 (d, J = 2.2 Hz, 1H) Mass spectrometric value (ESI-MS, m/z): 420 (M+1)+

Reference： [1]Current Patent Assignee: Kyowa Kirin (in: Kirin Holdings); KIRIN HOLDINGS CO., LTD. - EP1724268, 2006, A1 Location in patent: Page/Page column 44

17
[ 863783-73-7 ]
[ 87199-18-6 ]
3-[4-(5,6-Dimethyl-[2,2']bipyridinyl-3-yloxy)-quinolin-7-yl]-phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate In water; N,N-dimethyl-formamide at 70℃; for 5h;	106 N,N-Dimethylformamide (1 ml) and a 2 M aqueous potassium carbonate solution (0.5 ml) were added to 3-(7-Bromo-quinolin-4-yloxy)-5,6-dimethyl-[2,2']bipyridine (compound 14) (30 mg), tetrakistriphenylphosphine palladium (9 mg), and 3-hydroxyphenylboric acid (31 mg) under an argon atmosphere, and the mixture was stirred at 70°C for 5 hr. The reaction mixture was cooled to room temperature, water was added to the cooled mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then extracted with 1 N hydrochloric acid, and the aqueous layer was washed with ethyl acetate. The aqueous layer was rendered alkaline by the addition of potassium carbonate and was extracted with ethyl acetate. The ethyl acetate layer was washed with water and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography with a hexane-acetone system to give the title compound (31 mg, yield 100%). 1H-NMR (DMSO-d6, 400 MHz): δ 2.35 (s, 3H), 2.54 (s, 3H), 6.49 (d, J = 5.1 Hz, 1H), 6.83 (ddd, J = 8.0, 2.4, 1.0 Hz, 1H), 7.16 - 7.27 (m, 3H), 7.33 (dd, J = 7.8, 7.8 Hz, 1H), 7.66 (s, 1H), 7.76 (ddd, J = 7.8, 7.8, 2.0 Hz, 1H), 7.83 - 7.89 (m, 2H), 8.11 (d, J = 1.7 Hz, 1H), 8.20 - 8.23 (m, 2H), 8.31 (d, J = 1.8 Hz, 1H), 8.57 (d, J = 5.1 Hz, 1H) Mass spectrometric value (ESI-MS, m/z): 418 (M-1)-

Reference： [1]Current Patent Assignee: Kyowa Kirin (in: Kirin Holdings); KIRIN HOLDINGS CO., LTD. - EP1724268, 2006, A1 Location in patent: Page/Page column 74

18
[ 87199-18-6 ]
[ 120157-97-3 ]
[ 921625-82-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; tricyclohexylphosphine;palladium diacetate; In 1,4-dioxane; water; at 90℃; for 3h;Micro wave conditions;	A mixture of [2-(4-bromo-phenyl)-ethyl]-carbamic acid tert-butyl ester (500 mg), 3-hydroxy- benzeneboronic acid (296 mg), sodium carbonate (265 mg), palladium (II) acetate (7 mg) and tricyclohexylphosphine (10 mg) in water (3 ml) and dioxane (12 ml) is kept at 90C under micro wave conditions for 180 min. The mixture is cooled down to rt and is filtered through an EXTUBE extraction column (Varian) with EtOAc ( 200 ml). The filtrate is evaporated and the resulting crude product is purified on silica (15Og) with cyclohexane /EtOAc 5/1 to afford pure [2-(3'-hydroxy-biphenyl-4-yl)-ethyl]-carbamic acid tert-butyl ester.MS (ESI+): 336 [M+Na]; Rf: (EtOAc/hexane = 1/2): 0.28.

Reference： [1]Patent: WO2007/9715,2007,A1 .Location in patent: Page/Page column 34

19
[ 68819-84-1 ]
[ 87199-18-6 ]
[ 880156-96-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; tricyclohexylphosphine;palladium diacetate; In 1,4-dioxane; water; at 90℃; for 3.83333h;Micro wave conditions;	(3'-Hydroxy-biphenyl-4-ylmethyl)-carbamic acid tert-butyl ester A mixture of (4-bromo-benzyl)-carbamic acid tert-butyl ester (600 mg), 3-hydroxybenzene- boronic acid (373 mg), sodium carbonate (333 mg), palladium (II) acetate (10 mg) and tri- cyclohexylphosphine (13 mg) in water (3.5 ml) and dioxane (14 ml) is kept at 900C under micro wave conditions for 230 min. The mixture is cooled down to rt and is filtered through an EXTUBE extraction column with EtOAc ( 200 ml). The filtrate is evaporated and the resulting crude product is purified on silica (9Og) with cyclohexane /EtOAc 95:5 to 70:30 to afford pure (3'-hydroxy-biphenyl-4-ylmethyl)-carbamic acid tert-butyl ester.MS (ESI+): 322 [M+Na]; Rf: (EtOAc/hexane = 1/2): 0.28.

Reference： [1]Patent: WO2007/9715,2007,A1 .Location in patent: Page/Page column 30

20
[ 3934-20-1 ]
[ 87199-18-6 ]
[ 937271-43-7 ]

Yield	Reaction Conditions	Operation in experiment
88%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾ In 1,2-dimethoxyethane at 80℃; for 7h; Inert atmosphere; Alkaline aq. solution;
88%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾ In 1,2-dimethoxyethane at 80℃;
61.6%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium fluoride dihydrate In 1,4-dioxane; water at 90℃; for 4h; Inert atmosphere;	4.2.1 3-(2-Chloropyrimidin-4-yl)phenol (4) To a degassed (nitrogen) solution of 2,4-dichloropyrimidine (10g, 67.1mmol) and (3-hydroxyphenyl)boronic acid (11.1g, 80.5mmol) in dioxane (100mL) were added KF2H2O (25.5g, 268.4mmol), Pd(PPh3)4 (5.4g, 4.7mmol) and 5mL of water. The reaction mixture was heated at 90°C for 4h. After cooling to room temperature, it was filtered and the filtrate was concentrated under reduced pressure to give the reddish-brown residue, which was purified by recrystallization from ethyl acetate. Compound 4 was obtained as a yellowish solid (8.5g, 61.6%). 1HNMR (400MHz, DMSO-d6, δ): 9.83 (s, 1H), 8.80 (d, J=5.2Hz, 1H), 8.07 (d, J=5.2Hz, 1H), 7.63-7.61 (m, 2H), 7.38 (t, J=8.0Hz, 1H), 6.99 (ddd, J=8.0Hz, J=2.4Hz, J=1.0Hz, 1H); MS m/z: [M+H]+ 207.

40%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In 1,2-dimethoxyethane; water at 80 - 85℃; for 4h; Inert atmosphere;
26%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In 1,2-dimethoxyethane; water at 80℃;
23%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In tetrahydrofuran; water at 90℃; for 16h;	1.1 Step 1: 3-(2-chloropyrimidin-4-yl)phenol (intermediate 1) To 5 g (33.6 mmol) of 2,4-dichloropyrimidine in 250 mL of anhydrous tetrahydrofuran (THF) is added 4.41 g (32 mmol) of (3-hydroxyphenyl)boronic acid. The reaction mixture is stirred at room temperature for 10 minutes then 8.47 g (80 mmol) of sodium carbonate dissolved in 20 mL of water then 462 mg (1.59 mmol) of tetrakis(triphenylphosphine)palladium(0) is added at room temperature. The reaction mixture is stirred at 90° C. for 16 hours. Ethyl acetate is added and the organic phase is washed with saturated sodium chloride solution, dried over magnesium sulfate and filtered. The filtrate is evaporated and the residue purified by silica column chromatography using Companion (eluent: cyclohexane/ethyl acetate: 0 to 10%) to afford 1.54 g (23%) of 3-(2-chloropyrimidin-4-yl)phenol as a white solid. (0277) LCMS (EI, m/z): (M+1) 207.62 (0278) 1H NMR: dH ppm (400 MHz, DMSO): 9.82 (1H, s, OH), 8.79-8.80 (1H, d, CHarom), 8.06-8.08 (1H, d, CHarom), 7.61-7.62 (2H, m, CHarom), 7.35-7.39 (1H, d, CHarom), 6.99-7.01 (1H, t, CHarom)
	With sodium carbonate In 1,2-dimethoxyethane at 80 - 85℃; for 4h;	3-(2-Chloro-pyrimidin-4-yl)-phenoI (XIIIaI); (XIIaI) (Ia) (XIIIaI)To a degassed solution of (Ia) (1.Og, 6.71 mmol) and (XIIaI) (1.1g, 8.05 mmol) in 1 ,2 dimethoxy ethane (10 mL) was added sequentially, aqueous Na2CO3 ((1.06g, 10.06 mmol) and Pd(PPh3)4 (0.387g, 0.335 mmol). The resultant mixture was stirred at 80-85 O0C for 4 h, cooled to O0C and quenched with saturated NH4CI. The product was extracted with CH2CI2 thrice and the combined organic extracts were washed brine, dried over Na2SO4 and concentrated under reduced pressure. The crude mixture was column purified (EtOAc/Hexane) to furnish 0.450 g of (XIIIaI). LC-MS (ESI positive mode) m/z 207 ([M+H]+); 1H NMR (400MHz, CDCI3): δ 9.74 (s, 1 H), 9.23 (d, 1 H), 8.83 (d, 1 H)1 8.01 (dd, 1 H), 7.60-7.65 (m, 1 H), 7.35 (t, 1 H), 6.94-6.99 (m, 1H).
	With palladium diacetate In tetrahydrofuran	1 Example 1 Processes for the synthesis of 14-methyl-20-Oxa-5,7,14,27-tetraazatetracyclo-[19.3.1.12,6.18,12]heptacosa-1(25),2,4,6,8,10,12(26),16,21,23-decaene (Compound I) As illustrated in Scheme 1, 2,4-dichloropyrimidine (1) was subjected to a palladium (II)-mediated cross-coupling reaction with 3-hydroxyphenylboronic acid (2) to give the 4-substituted pyrimidine 3. Alkylation with 1-bromo-3-butene followed by condensation with aniline 7 afforded the tricyclic alkene 8. Subjecting compound 8 to the ring closing metathesis reaction provided Compound I which was isolated as the hydrochloride salt.
0.45 g	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In 1,2-dimethoxyethane; water at 80 - 85℃; for 4h; Inert atmosphere;	3.1 Synthesis Example 3: Preparation of intermediate 7 (IM-16-2) Step 1: to a degassed solution of 2,4-dichloropyrimidine (7 mmol) and (3- hydroxyphenyl)boronic acid (8 mmol) in 1 ,2 dimethoxy ethane (10 mL) was added sequentially, aqueous Na2C03 (10 mmol) and Pd(PPh3)4 (0.335 mmol). The resultant mixture was stirred at 80-85°C for 4 h, cooled to 0°C and quenched with saturated aqueous NH4CI solution. The product was extracted with CH2CI2 thrice and the combined organic extracts were washed with brine, dried over Na2S04 and concentrated under reduced pressure. The crude mixture was column purified (EtOAc/Hexane) to obtain 0.45g of intermediate 5. 1H NMR (400MHz, CDCI3): δ 9.74 (s, 1 H)i 9.23 (d, 1 H), 8.83 (d, 1 H), 8.01 (dd, 1 H), 7.60-7.65 (m, 1H), 7.35 (t, 1H), 6.94-6.99 (m, 1H). MS (m/z): 207 [MH]+.
	Stage #1: 2,6-Dichloropyrimidine; 3-hydroxyphenylboronic acid With sodium carbonate In 1,2-dimethoxyethane; water at 80 - 85℃; for 4h; Stage #2: With ammonium chloride In 1,2-dimethoxyethane; water at 0℃;	1.1a.1 Example 1a; Preparation of 4-(3-But-3-enyloxy-phenyl)-2-chloro-pyrimidine (Ia); XIM IaStep 1 : 3-{2-Chloro-pyrimidin-4-yl)-phenol (XIM); To a degassed solution of X-1 (1.0 g, 6.71 mmol) and XI-1 (1.1 g, 8.05 mmol) in 1 ,2-dimethoxy ethane (10 ml_) was added sequentially, aqueous Na2CO3 (1.06 g, 10.06 mmol) and Pd(PPh3)4 (0.387 g, 0.335 mmol). The resultant mixture was stirred at 80-850C for 4 h, cooled to O0C and quenched with saturated aqueous NH4CI solution The product was extracted with CH2CI2 thrice and the combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude mixture was purified by flash column chromatography (EtOAc/Hexane) to furnish 0.450 g of XIM.LC-MS m/z: 207 ([MH]+). 1H NMR (CDCI3) δ 9.74 (s, 1H), 9.23 (d, 1 H), 8.83 (d, 1H), 8.01(dd, 1 H), 7.60-7.65 (m, 1H), 7.35 (t, 1 H), 6.94-6.99 (m, 1 H).

Reference： [1]Location in patent: experimental part William, Anthony D.; Lee, Angeline C.-H.; Goh, Kee Chuan; Blanchard, Stéphanie; Poulsen, Anders; Teo, Ee Ling; Nagaraj, Harish; Lee, Chai Ping; Wang, Haishan; Williams, Meredith; Sun, Eric T.; Hu, Changyong; Jayaraman, Ramesh; Pasha, Mohammed Khalid; Ethirajulu, Kantharaj; Wood, Jeanette M.; Dymock, Brian W. [Journal of Medicinal Chemistry, 2012, vol. 55, # 1, p. 169 - 196]
[2]William, Anthony D.; Lee, Angeline C.-H. [Chimia, 2015, vol. 69, # 3, p. 142 - 145]
[3]Ning, Cheng-Qing; Lu, Cheng; Hu, Liang; Bi, Yan-Jing; Yao, Lei; He, Yu-Jun; Liu, Li-Fei; Liu, Xiao-Yu; Yu, Nie-Fang [European Journal of Medicinal Chemistry, 2015, vol. 95, p. 104 - 115]
[4]Location in patent: experimental part William, Anthony D.; Lee, Angeline C.-H.; Blanchard, Stéphanie; Poulsen, Anders; Teo, Ee Ling; Nagaraj, Harish; Tan, Evelyn; Chen, Dizhong; Williams, Meredith; Sun, Eric T.; Goh, Kee Chuan; Ong, Wai Chung; Goh, Siok Kun; Hart, Stefan; Jayaraman, Ramesh; Pasha, Mohammed Khalid; Ethirajulu, Kantharaj; Wood, Jeanette M.; Dymock, Brian W. [Journal of Medicinal Chemistry, 2011, vol. 54, # 13, p. 4638 - 4658]
[5]Monty, Olivier B. C.; Nyshadham, Pranavanand; Bohren, Kurt M.; Palaniappan, Murugesan; Matzuk, Martin M.; Young, Damian W.; Simmons, Nicholas [ACS Combinatorial Science, 2020, vol. 22, # 2, p. 80 - 88]
[6]Current Patent Assignee: PIERRE FABRE PARCIPATIONS - US2017/281622, 2017, A1 Location in patent: Paragraph 0275-0278
[7]Current Patent Assignee: CTI BIOPHARMA CORP. - WO2007/58627, 2007, A1 Location in patent: Page/Page column 72
[8]Current Patent Assignee: COTHERA BIOSCIENCE - US9120815, 2015, B2 Location in patent: Page/Page column 18-19
[9]Current Patent Assignee: NEWAVE PHARMACEUTICAL INC - WO2016/149031, 2016, A1 Location in patent: Page/Page column 59-60
[10]Current Patent Assignee: S BIO - WO2008/140420, 2008, A2 Location in patent: Page/Page column 64

21
[ 871116-69-7 ]
[ 87199-18-6 ]
3-((1H-1,2,4-triazol-1-yl)methyl)-3'-hydroxybiphenyl-4-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With tetrabutylammomium bromide; potassium carbonate In ethanol; water at 120℃; for 0.05h; Irradiation;	3 '-Hydroxy-3- [1 ,2,4] triazol-1-ylmethy I-biphenyI-4-carbonitriIe (TJA01141, STX1843) C16H12N4O MW 276.29. A 10 mL microwave vial was loaded with TJA01046 (0.200 g, 0.760 mmol), 3- hydroxyphenylboronic acid (0.160 g, 1.14 mmol), potassium carbonate (0.263 g, 1.90 mmol), tetrabutylammonium bromide (0.253 g, 0.760 mmol), Pd(OAc)2 (0.005-0.006 g, 2-3 mol %), ethanol (1.5 mL) and distilled water (3.5 mL). The vial was sealed and loaded (with no prior degassing) into a CEM Discover Microwave. After a run time of 3 min at 120 0C the reaction mixture was allowed to cool and ethyl acetate (50 mL) added.This was then washed with distilled water (30 mL x 3) and brine (30 mL). The organic layer was dried over MgSO4, filtered and solvent removed in vacuo to leave a yellow/brown residue. The crude product was purified by flash chromatography (20 g column, methodT) eluting the title compound as a white solid (0.184 g, 89 %), mp 182.7-184.3 0C;Rf. 0.33 (ethyl acetate);1HNMR (270 MHz, DMSO-d6) δ 5.68 (2H, s, ArCH2N), 6.83-6.87 (IH5 dd, J= 2.5 & 8.2 Hz, ArH), 7.01-7.10 (2H, m, ArH)5 7.28-7.34 (IH, t, J= 7.9 Hz, ArH)5 7.68 (IH5 s, ArH)57.76-7.79 (IH5 dd, J= 1.8 & 8.1 Hz, ArH), 7.93-7.96 (IH5 d, J= 8.2 Hz5 ArH), 8.06 (IH5 S5C2H2N3), 8.75 (IH5 S5 C2H2N3) and 9.73 (IH, S5 ArOH);13C NMR (67.9 MHz5 DMSO-^6) δ 51.0 (CH2), 110.5 (C)5 114.2 (CH), 116.5 (CH),117.7 (C)5 118.3 (CH), 127.6 (CH), 128.4 (CH)5 130.9 (CH), 134.5 (CH)5 139.8 (C)5 140.2 (C), 145.5 (CH), 145.6 (C)5 152.7 (CH) and 158.6 (C);HPLC (90 % CH3CN in H2O) tτ= 1.963 (100 %); LCMS (APCI), m/z 277.39 (M++ H, 100 %).
89%	With tetrabutylammomium bromide; palladium diacetate; potassium carbonate In ethanol; water at 120℃; Microwave irradiation;

Reference： [1]Current Patent Assignee: IPSEN SA - WO2007/68905, 2007, A1 Location in patent: Page/Page column 117-118
[2]Location in patent: experimental part Lawrence Woo; Jackson, Toby; Putey, Aurélien; Cozier, Gyles; Leonard, Philip; Ravi Acharya; Chander, Surinder K.; Purohit, Atul; Reed, Michael J.; Potter, Barry V. L. [Journal of Medicinal Chemistry, 2010, vol. 53, # 5, p. 2155 - 2170]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; at 150℃; for 3h;Reactivity (does not react);	No evidence of product formation corresponding to xanthene structure.

23
[ 905590-33-2 ]
aqueous potassium carbonate [ No CAS ]
[ 87199-18-6 ]
[ 247940-06-3 ]
4-(3,4-diethoxyphenyl)-N-[4-(3-hydroxyphenyl)-6-phenylpyridin-2-yl]-4-oxobutanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0);	Example 134 4-(3,4-diethoxyphenyl)-N-[4-(3-hydroxyphenyl)-6-phenylpyridin-2-yl]-4-oxobutanamide Using N-(4-chloro-6-phenylpyridin-2-yl)-4-(3,4-diethoxyphenyl)-4-oxobutanamide obtained in Example 43-(3) (22.6 mg), tris(dibenzylideneacetone)dipalladium (1.1 mg), biphenyl-2-yl(dicyclohexyl)phosphine (1.8 mg), 1N aqueous potassium carbonate solution (0.1 mL) and (3-hydroxyphenyl)boronic acid (17.2 mg) as starting materials and in the same manner as in Example 119, 4-(3,4-diethoxyphenyl)-N-[4-(3-hydroxyphenyl)-6-phenylpyridin-2-yl]-4-oxobutanamide (11.0 mg) was obtained. HPLC (220 nm) purity 91% (retention time 1.94 min) MS (ESI+, m/e) 511 (M+H)

Reference： [1]Patent: EP1845081,2007,A1

24
[ 905590-58-1 ]
aqueous potassium carbonate [ No CAS ]
[ 87199-18-6 ]
[ 247940-06-3 ]
4-(2,3-dihydro-1-benzofuran-5-yl)-N-[4-(3-hydroxyphenyl)-6-phenylpyridin-2-yl]-4-oxobutanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0);	Example 165 4-(2,3-dihydro-1-benzofuran-5-yl)-N-[4-(3-hydroxyphenyl)-6-phenylpyridin-2-yl]-4-oxobutanamide Using N-(4-chloro-6-phenylpyridin-2-yl)-4-(2,3-dihydro-1-benzofuran-5-yl)-4-oxobutanamide obtained in Example 114-(1) (20.3 mg), tris(dibenzylideneacetone)dipalladium (1.1 mg), biphenyl-2-yl(dicyclohexyl)phosphine (1.8 mg), 1N aqueous potassium carbonate solution (0.1 mL) and (3-hydroxyphenyl)boronic acid (17.2 mg) as starting materials and in the same manner as in Example 119, 4-(2,3-dihydro-1-benzofuran-5-yl)-N-[4-(3-hydroxyphenyl)-6-phenylpyridin-2-yl]-4-oxobutanamide (11.5 mg) was obtained. HPLC (220 nm) purity 91% (retention time 1.88 min) MS (ESI+, m/e) 465 (M+H)

Reference： [1]Patent: EP1845081,2007,A1

25
[ 1020329-80-9 ]
[ 87199-18-6 ]
[ 1020329-87-6 ]

Yield	Reaction Conditions	Operation in experiment
66%	With potassium phosphate In tetrahydrofuran; water at 50℃; for 1.5h;	57.3 Step 3 tert-Butyl 4-(3-hydroxybenzylidene)piperidine-1-carboxylate To a solution of tert-butyl 4-(bromomethylene)piperidine-1-carboxylate (38 g, 0.1376 mol) in dry THF (380 mL) was added 3-hydroxyphenyl boronic acid (22.77 g, 0.165 mol), potassium phosphate (88.2 g, 0.415 mol) and water (7.6 mL). The mixture was degassed with argon. 1,1'-Bis(diphenylphosphino)ferrocene palladium(II) dichloride dichloromethane complex (11.23 g, 0.01376 mol) was added and the mixture was degassed again. The reaction was heated at 50° C. for 1.5 h and then allowed to cool to RT. Water was added and the mixture was extracted with ethyl acetate (3*). The total organic extract was washed with brine, dried over sodium sulfate and evaporated to dryness. The residue was purified by silica gel chromatography using 100-200 mesh silica gel (8% ethyl acetate in hexane) to give the title compound (26.3 g, 66%). 1H NMR (500 MHz, CDCl3): δ 7.16 (t, J=7.5 Hz, 1H), 6.74 (d, J=7.5 Hz, 1H), 6.68 (d, J=9 Hz, 1H), 6.68 (s, 1H), 6.30 (s, 1H), 5.37 (bs, 1H), 3.49 (m, 2H), 3.40 (m, 2H), 2.46 (m, 2H), 2.31 (m, 2H), 1.48 (s, 9H); 13C NMR (125 MHz, CDCl3): δ 156.09, 155.09, 138.87, 138.15, 129.31, 124.58, 120.98, 115.74, 113.54, 80.10, 45.45, 44.57, 36.08, 29.23, 28.50.
66%	With potassium phosphate In tetrahydrofuran; water at 50℃; for 1.5h; Inert atmosphere;	To a solution of tert-butyl 4-(bromomethylene)piperidine-1-carboxylate (38 g, 0.1376 mol) in dry THF (380 mL) was added 3-hydroxyphenyl boronic acid (22.77 g, 0.165 mol), potassium phosphate (88.2 g, 0.415 mol) and water (7.6 mL). The mixture was degassed with argon. 1,1'-Bis(diphenylphosphino)ferrocene palladium(ll) dichloride dichloromethane complex (11.23 g, 0.01376 mol) was added and the mixture was degassed again. The reaction was heated at 500C for 1.5 h and then allowed to cool to RT. Water was added and the mixture was extracted with ethyl acetate (3x). The total organic extract was washed with brine, dried over sodium sulfate and evaporated to dryness. The residue was purified by silica gel chromatography using 100-200 mesh silica gel (8% ethyl acetate in hexane) to give the title compound (26.3 g, 66 %). 1H NMR (500 MHz, CDCI3): δ 7.16 (t, J = 7.5 Hz, 1 H), 6.74 (d, J = 7.5 Hz, 1 H), 6.68 (d, J = 9 Hz, 1 H), 6.68 (s, 1 H), 6.30 (s, 1 H), 5.37 (bs, 1 H), 3.49 (m, 2 H), 3.40 (m, 2 H), 2.46 (m, 2 H), 2.31 (m, 2 H), 1.48 (S, 9 H).
66%	With potassium phosphate In tetrahydrofuran; water at 50℃; for 1.5h; Inert atmosphere;	To a solution of tert-butyl 4-(bromomethylene)piperidine-1-carboxylate (38 g, 0.1376 mol) in dry THF (380 mL) was added 3-hydroxyphenyl boronic acid (22.77 g, 0.165 mol), potassium phosphate (88.2 g, 0.415 mol) and water (7.6 mL). The mixture was degassed with argon. 1,1'-Bis(diphenylphosphino)ferrocene palladium(ll) dichloride dichloromethane complex (11.23 g, 0.01376 mol) was added and the mixture was degassed again. The reaction was heated at 50 0C for 1.5 h and then allowed to cool to RT. Water was added and the mixture was extracted with ethyl acetate (3x). The total organic extract was washed with brine, dried over sodium sulfate and evaporated to dryness. The residue was purified by silica gel chromatography using 100-200 mesh silica gel (8% ethyl acetate in hexane) to give the title compound (26.3 g, 66 %). 1H NMR (500 MHz, CDCI3): δ 7.16 (t, J = 7.5 Hz, 1 H), 6.74 (d, J = 7.5 Hz, 1 H), 6.68 (d, J = 9 Hz, 1 H), 6.68 (s, 1 H)1 6.30 (s, 1 H), 5.37 (bs, 1 H), 3.49 (m, 2 H), 3.40 (m, 2 H), 2.46 (m, 2 H), 2.31 (m, 2 H), 1.48 (s, 9 H).

Reference： [1]Current Patent Assignee: PFIZER INC - US2008/261941, 2008, A1 Location in patent: Page/Page column 37
[2]Current Patent Assignee: PFIZER INC - WO2009/127943, 2009, A1 Location in patent: Page/Page column 27
[3]Current Patent Assignee: PFIZER INC - WO2009/127944, 2009, A1 Location in patent: Page/Page column 27

26
[ 4010-81-5 ]
[ 87199-18-6 ]
[ 934545-07-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 180℃; for 1h;	A mixture of <strong>[4010-81-5]4-(2-chloro-9H-purin-6-yl)morpholine</strong> (0.18 g, 0.75 mmol), tetrakis(triphenylphosphine)palladium (30 mg), and 3-hydroxyphenylboronic acid (0.16 g, 1.1 mmol) in 1,2-dimethoxyethane (2.6 mL) and 2 M aqueous sodium carbonate (0.75 mL) was heated in a microwave reactor for one hour at 180 C. After being allowed to cool to room temperature, the mixture was acidified with 5% aqueous potassium hydrogen sulfate solution and then extracted with ethyl acetate. Organics were washed successively with water and saturated aqueous sodium hydrogen carbonate solution, then dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to afford a crude white solid. The crude material was purified by reverse phase HPLC, employing a gradient elution of 85% A solvent (0.1% aqueous trifluoroacetic acid) to 100% B solvent (acetonitrile) to afford 3-(6-morpholino-9H-purin-2-yl)phenol as a white powder (80 mg). MS (ES+): 298.0 (M+H)+

Reference： [1]Patent: US2008/233127,2008,A1 .Location in patent: Page/Page column 37
[2]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 636 - 639
[3]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 653 - 656

27
[ 1093871-51-2 ]
[ 87199-18-6 ]
[ 1093871-17-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium phosphate In water; toluene at 85℃; for 2.5h;	N-f3-f3-Hydroxyphenyl)-l-methyl-lH-pyrazolo[3,4-blpyridine-5-yl)acetamide (A.4): Palladium acetate (35.5 mg, 0.16 mmol, 0.05 eq.) is added to a suspension of 5a (1.0 g, 3.16 mmol), 3-hydroxyphenyl boronic acid (698 mg, 5.10 mmol, 1.6 eq.), potassium phosphate (1.34 g, 6.33 mmol, 2 eq.), (2-biphenyl)dicyclohexyl phosphine (111 mg, 0.32 mmol, 0.1 eq.) in a degassed mixture of toluene: water (36 mL, 5:1). The reaction mixture is stirred under an atmosphere of nitrogen at 85 0C for 2.5 h. The reaction is filtered, the solid collected and washed with toluene (50 mL), water (2x50 mL), then diethyl ether (2x50 mL). The crude material is purified by flash column chromatography over silica gel, eluting with hexanes:ethyl acetate methanol (5:5:0.2 to 5:5:1) to afford 755 mg (85 %) of the title compound A.4. Ci5Hi4N4O2 (282.3): MS-APCI: 282.9 ([M+H]+). HPLC (Method A) R1 in min (purity) = 3.11 (100).

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2009/832, 2008, A2 Location in patent: Page/Page column 20-21

28
[ 104-92-7 ]
[ 87199-18-6 ]
[ 33104-27-7 ]

Yield	Reaction Conditions	Operation in experiment
91%	With palladium diacetate; potassium carbonate In tetrahydrofuran; water monomer for 5h; Inert atmosphere; Reflux;
78%	With palladium diacetate; potassium carbonate In water monomer; acetone at 20℃; for 0.333333h; Inert atmosphere;	PATHWAY G PATHWAY G Nitrogen was bubbled through a mixture of 1-bromo-4-methoxybenzene (5.0 g, 26.8 mmol), 3-hydroxyphenylboronic acid (6.8 g, 49.6 mmol), aqueous potassium carbonate (2 M, 20 mL, 40 mmol), acetone (170 mL) and H20 (300 mL) for 5 minutes. Pd(OAc)2 (800 mg,3.55 mmol) was added and the mixture was stirred under a nitrogen atmosphere at room temperature for 20 minutes, after which time LC-MS analysis showed the reaction to be complete. The reaction mixture was concentrated under vacuum then diluted with ethyl acetate (200 mL). The resulting suspension was filtered through a pad of celite, and the aqueous phase was then separated and extracted with EtOAc (2 x 100 mL). The combined organics were dried over MgSO4, filtered and concentrated to dryness under vacuum. The crude product was loaded onto a 340 g Biotage silica cartridge and purified by Biotage chromatography (eluting with iso-hexane/EtOAc, gradient 0 to 50 %). The target compound 4’-methoxy-[1,1’-biphenyll-3-ol was isolated as a white solid (5.66 g, 78 % yield).
78%	With palladium diacetate; potassium carbonate In water monomer; acetone at 20℃; for 0.416667h; Inert atmosphere;	G Pathway G Nitrogen was bubbled through a mixture of 1-bromo-4-methoxybenzene (5.0 g, 26.8 mmol), 3-hydroxyphenylboronic acid (6.8 g, 49.6 mmol), aqueous potassium carbonate (2 M, 20 mL, 40 mmol), acetone (170 mL) and H2O (300 mL) for 5 minutes. Pd(OAc)2 (800 mg, 3.55 mmol) was added and the mixture was stirred under a nitrogen atmosphere at room temperature for 20 minutes, after which time LC-MS analysis showed the reaction to be complete. The reaction mixture was concentrated under vacuum then diluted with ethyl acetate (200 mL). The resulting suspension was filtered through a pad of celite, and the aqueous phase was then separated and extracted with EtOAc (2×100 mL). The combined organics were dried over MgSO4, filtered and concentrated to dryness under vacuum. The crude product was loaded onto a 340 g Biotage silica cartridge and purified by Biotage chromatography (eluting with iso-hexane/EtOAc, gradient 0 to 50%). The target compound 4′-methoxy-[1,1′-biphenyl]-3-ol was isolated as a white solid (5.66 g, 78% yield).

74.8%	With tetrakis-(triphenylphosphine)-palladium; anhydrous sodium carbonate In ethanol; water monomer; toluene at 80℃; for 12h;	1. 2-(2-fluoro-4-(((4'-methoxy-[1,1'-biphenyl]-3-yl)oxy)methyl)phenoxy)acetic acid (compound 17) (3-hydroxyphenyl)boronic acid (0.37 g, 2.67 mmol), 14a (0.50 g, 2.67 mmol), Pd(PPh3)4 (0.37 g, 0.32 mmol) and sodium carbonate (0.85 g, 8.02 mmol) in toluene/ethanol/H2O (35 mL, 3/1/3) was refluxed under nitrogen atmosphere for 24 h. Then the mixture was diluted with saturated ammonium chloride solution and ethyl acetate, and the insoluble material was filtered through Celite. The organic layer of the filtrate was washed with water (25 mL) and brine (25 mL), dried over anhydrous sodium sulfate, and evaporated in vacuo. The residue was purified by column chromatography using a mixture of petroleum petroleum ether /ethyl acetate (10:1, v/v) as eluent to afford the desired product 15a 0.4 g (yield: 74.8%) as a white solid.
74.8%	With tetrakis-(triphenylphosphine)-palladium; anhydrous sodium carbonate In ethanol; water monomer; toluene at 80℃; for 12h;	1. 2-(2-fluoro-4-(((4'-methoxy-[1,1'-biphenyl]-3-yl)oxy)methyl)phenoxy)acetic acid (compound 17) (3-hydroxyphenyl)boronic acid (0.37 g, 2.67 mmol), 14a (0.50 g, 2.67 mmol), Pd(PPh3)4 (0.37 g, 0.32 mmol) and sodium carbonate (0.85 g, 8.02 mmol) in toluene/ethanol/H2O (35 mL, 3/1/3) was refluxed under nitrogen atmosphere for 24 h. Then the mixture was diluted with saturated ammonium chloride solution and ethyl acetate, and the insoluble material was filtered through Celite. The organic layer of the filtrate was washed with water (25 mL) and brine (25 mL), dried over anhydrous sodium sulfate, and evaporated in vacuo. The residue was purified by column chromatography using a mixture of petroleum petroleum ether /ethyl acetate (10:1, v/v) as eluent to afford the desired product 15a 0.4 g (yield: 74.8%) as a white solid.
69%	With palladium 10% on activated carbon; n-tetrabutylammonium fluoride trihydrate at 150℃; for 0.5h; Microwave irradiation; Inert atmosphere;

Reference： [1]Razler, Thomas M.; Hsiao, Yi; Qian, Feng; Fu, Ruiling; Khan, Rana Kashif; Doubleday, Wendel [Journal of Organic Chemistry, 2009, vol. 74, # 3, p. 1381 - 1384]
[2]Current Patent Assignee: ATXA THERAPEUTICS - WO2013/156861, 2013, A2 Location in patent: Page/Page column 35
[3]Current Patent Assignee: ATXA THERAPEUTICS - US2016/102051, 2016, A1 Location in patent: Paragraph 0094-0095
[4]Cai, Zongyu; Deng, Liming; Geng, Xinqian; Hu, Lijun; Jiao, Shixuan; Li, Zheng; Ren, Qiang; Wang, Bin; Yang, Ying; Zhang, Luyong; Zhou, Zongtao [European Journal of Medicinal Chemistry, 2022, vol. 229]
[5]Cai, Zongyu; Deng, Liming; Geng, Xinqian; Hu, Lijun; Jiao, Shixuan; Li, Zheng; Ren, Qiang; Wang, Bin; Yang, Ying; Zhang, Luyong; Zhou, Zongtao [European Journal of Medicinal Chemistry, 2022, vol. 229]
[6]Schmidt, Bernd; Riemer, Martin [Journal of Organic Chemistry, 2014, vol. 79, # 9, p. 4104 - 4118]

29
[ 1174766-04-1 ]
[ 87199-18-6 ]
C₂₆H₃₁N₅O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium carbonate In 1,2-dimethoxyethane; water at 130℃; for 0.5h; Microwave irradiation;	40 Preparation of 3-[6-(3,6-dihydro-2H-pyran-4-yl)-9-piperidin-4-yl-9H-purin-2-yl]phenolExample 40To a microwave processing tube dimethoxyethane (2 mL), aqueous Na2CO3 (2 molar) (0.5 mL, 1 mmol), (Ph3P)4Pd (66 mg, 0.05 mmol), 3-hydroxyphenyl-boronic acid (108 mg, 0.78 mmol, 1.6 eq) and tert-butyl 4-(2-chloro-6-(3,6-dihydro-2H-pyran-4-yl)-9H-purin-9-yl)piperidine-1-carboxylate (200 mg, 0.48 mmol) were added and the vessel was sealed. The mixture was heated to 130° C. for 30 minutes. The solvents were removed on a rotary evaporator and the crude compound was purified by silica gel chromatography (50% hexane/EtOAc) to give the product as a white solid (200 mg, 87% yield).

Reference： [1]Current Patent Assignee: PFIZER INC - US2009/192176, 2009, A1 Location in patent: Page/Page column 43

30
[ 1202885-73-1 ]
[ 87199-18-6 ]
[ 1202884-49-8 ]

Yield	Reaction Conditions	Operation in experiment
78%	With sodium carbonate In 1,2-dimethoxyethane at 150℃; for 0.666667h; Microwave irradiation;	6.2 Step 2: Synthesis of 3-{7-[2-(dimethylamino)ethyl]-4-morpholin-4-yl-7H-pyrrolo[2,3-d]pyrimidin-2-yl}phenol To a 10 mL vial were added 2-chloro-4-morpholin-4-yl-7-[2-(dimethylamino)ethyl]-7H-pyrrolo[2,3-d]pyrimidine (80 mg, 0.26 mmol), 3-hydroxyphenylboronic acid (54 mg, 0.38 mmol), Pd(PPh3)4 (15 mg, 5 mol %), 1,2-dimethoxyethane (DME, 3 mL) and sodium carbonate aqueous solution (2M, 2 mL). The resulting mixture was heated at 150° C. for 40 min in microwave oven, and then cooled to room temperature. The aqueous phase was extracted with EtOAc, and the combined organic solution was concentrated under reduced pressure. The residue was subjected to HPLC separation to give the title compound as off-white solid (81.9 mg, 78% yield). MS(ESI) m/z 368.4.
81.9 mg	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In 1,2-dimethoxyethane; water at 120℃; for 1h; Microwave irradiation;

Reference： [1]Current Patent Assignee: PFIZER INC - US2010/3250, 2010, A1 Location in patent: Page/Page column 21
[2]Location in patent: experimental part Chen, Zecheng; Venkatesan, Aranapakam M.; Dehnhardt, Christoph M.; Ayral-Kaloustian, Semiramis; Brooijmans, Natasja; Mallon, Robert; Feldberg, Larry; Hollander, Irwin; Lucas, Judy; Yu, Ker; Kong, Fangming; Mansour, Tarek S. [Journal of Medicinal Chemistry, 2010, vol. 53, # 8, p. 3169 - 3182]

31
[ 13191-36-1 ]
[ 87199-18-6 ]
[ 1193524-70-7 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 6724 - 6743

32
[ 23779-97-7 ]
[ 87199-18-6 ]
[ 854774-58-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 209 - 212

33
[ 21617-12-9 ]
[ 87199-18-6 ]
[ 1207842-25-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 209 - 212

34
[ 30483-75-1 ]
[ 87199-18-6 ]
[ 1233720-64-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3494 - 3505

35
[ 87199-18-6 ]
[ 836-59-9 ]
[ 1233720-65-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3494 - 3505

36
[ 87199-18-6 ]
[ 95162-14-4 ]
[ 1253690-71-9 ]

Reference： [1]Heterocycles,2010,vol. 81,p. 1509 - 1516

37
[ 76-09-5 ]
[ 87199-18-6 ]
[ 214360-76-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	In dichloromethane; at 20℃; for 48h;	To a 500 mL three-necked flask, 3-hydroxyphenylboronic acid (10.0 g, 72.46 mmol, 1.0 eq) and methylene chloride (300 mL) were added, and pinacol (10.0 g, 84.60 mmol, 1.2 eq) was added under stirring, followed by stirring at room temperature for 48 h. The reaction solution was poured into water (400 mL). The mixed solution was poured into a separatory funnel. The organic phase was separated and the aqueous phase was extracted twice with dichloromethane (400 mL). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The crude product was purified by column chromatography (200-300 mesh silica gel, methylene chloride/methanol mixed solvent at a volume ratio of 100/1 as eluent) to obtain 15.0 g of a white solid with a yield of 94% and a purity of 97%.

Reference： [1]Patent: CN107188901,2017,A .Location in patent: Paragraph 0035; 0036
[2]Organic Letters,2010,vol. 12,p. 5474 - 5477

38
[ 16239-18-2 ]
[ 87199-18-6 ]
[ 1064680-81-4 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 534 - 547

39
[ 1273189-69-7 ]
[ 87199-18-6 ]
[ 1273189-96-0 ]

Yield	Reaction Conditions	Operation in experiment
52%	With sodium carbonate In 1,2-dimethoxyethane; ethanol; water at 85℃; for 1h;	119 To 5 tert-butyl 5-chloro-3-formylpyrazolo[l,5-a]pyrimidin-7-yl(cyclopropyl)carbamate (650 mg, 1.93 mmol) in 14 mL of a 2: 1 mixture of 1,2- Dimethoxyethane/ EtOH was added 3-hydroxyphenyl boronic acid (399 mg, 2.89mmol), tetrakis(triphenylphosphine)palladium(0) (112 mg, 0.096 mmol), and 2M aqueous solution of Na2C03 (2.9 mL, 5.79 mmol). The mixture was stirred at 85°C for lh. The volatiles were removed by rotary evaporation and the residue was purified by silica gel chromatography (0%-30% EtOAc/Hexanes) to provide 400 mg of tert-butyl cyclopropyl(3-formyl-5-(3- hydroxyphenyl)pyrazolo[l,5-a]pyrimidin-7-yl)carbamate. (52%) ( LCMS (M+l=395)
52%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In 1,2-dimethoxyethane; ethanol at 85℃; for 1h;	38; 97 Synthesis of tert-butyl cyclopropyl(3-formyl-5-(3-hydroxyphenyl)pyrazolo[1,5-a]pyrimidin-7-yl)carbamate Example 97 Synthesis of tert-butyl cyclopropyl(3-formyl-5-(3-hydroxyphenyl)pyrazolo[1,5-a]pyrimidin-7-yl)carbamate To tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate (650 mg, 1.93 mmol) in 14 mL of a 2:1 mixture of 1,2-dimethoxyethane/EtOH was added 3-hydroxyphenyl boronic acid (399 mg, 2.89 mmol), tetrakis(triphenylphosphine)palladium(0) (112 mg, 0.096 mmol), and 2M aqueous solution of Na2CO3 (2.9 mL, 5.79 mmol). The mixture was stirred at 85° C. for 1 h. The volatiles were removed by rotary evaporation and the residue was purified by silica gel chromatography (0%-30% EtOAc/Hexanes) to provide 400 mg of tert-butyl cyclopropyl(3-formyl-5-(3-hydroxyphenyl)pyrazolo[1,5-a]pyrimidin-7-yl)carbamate. (52%). LCMS (M+1=395)
52%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In 1,2-dimethoxyethane; ethanol; water at 85℃; for 1h;	38; 97 Synthesis of tert-butyl cyclopropyl(3-formyl-5-(3-hydroxyphenyl)pyrazolo[1,5-a]pyrimidin-7-yl)carbamate To 5 tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate (650 mg, 1.93 mmol) in 14 mL of a 2:1 mixture of 1,2-dimethoxyethane/EtOH was added 3-hydroxyphenyl boronic acid (399 mg, 2.89 mmol), tetrakis(triphenylphosphine)palladium(0) (112 mg, 0.096 mmol), and 2M aqueous solution of Na 2CO 3 (2.9 mL, 5.79 mmol). The mixture was stirred at 85° C. for 1 h. The volatiles were removed by rotary evaporation and the residue was purified by silica gel chromatography (0%-30% EtOAc/Hexanes) to provide 400 mg of tert-butyl cyclopropyl(3-formyl-5-(3-hydroxyphenyl)pyrazolo[1,5-a]pyrimidin-7-yl)carbamate.

Reference： [1]Current Patent Assignee: SENHWA BIOSCIENCES - WO2011/31979, 2011, A1 Location in patent: Page/Page column 137
[2]Current Patent Assignee: SENHWA BIOSCIENCES - US9303033, 2016, B2 Location in patent: Page/Page column 179; 114
[3]Current Patent Assignee: SENHWA BIOSCIENCES - JP5802676, 2015, B2 Location in patent: Paragraph 0340

40
[ 87199-18-6 ]
[ 151266-23-8 ]
3-(4-amino-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With potassium phosphate In water; N,N-dimethyl-formamide at 120℃; for 2h; Inert atmosphere;	To a stirred suspension of 3-iodo-1 /-/-pyrazolo[3,4-c/]pyrimidin-4-amine (1 ) (8.22 g, 31 .5 mmol), 3-phenol boronic acid (13.0 g, 94.5 mmol) and potassium phosphate (10.0 g, 47.3 mmol) in degassed DMF/water (3:2, 140 mL) was added [dppf] palladium (II) dichloride (13.0 g, 15.7 mmol). The reaction mixture was flushed with nitrogen, heated at 120 C for 2 hr and then allowed to cool to RT. The reaction mixture was diluted with EtOAc (500 mL) and aqueous hydrochloric acid (2 M, 500 mL) and the resulting suspension was filtered. The filtrate was extracted with aqueous hydrochloric acid (2 M, 2 x 500 mL). The combined aqueous extracts were basified with a saturated aq solution of sodium carbonate to pH 10. The precipitate formed was filtered and the filtrate was extracted with EtOAc (3 x 1 L). The combined organic extracts were dried, filtered and the solvent removed in vacuo to afford a grey solid. All solid materials generated during the workup procedure were combined and triturated with DCM to afford 3-(4- amino-1 /-/-pyrazolo[3,4-c/]pyrimidin-3-yl)phenol (2) (6.04 g, 84%) as a grey solid: m/z 228 (M+H)+ (ES+).
84%	Stage #1: 3-hydroxyphenylboronic acid; 4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidine With potassium phosphate In water; N,N-dimethyl-formamide at 120℃; for 2h; Inert atmosphere; Stage #2: With hydrogenchloride In water; ethyl acetate; N,N-dimethyl-formamide Stage #3: With sodium carbonate In water	3-(3-(tert-Butyldimethylsilyloxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (3) To a stirred suspension of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1) (8.22 g, 31.5 mmol), 3-phenol boronic acid (13.0 g, 94.5 mmol) and potassium phosphate (10.0 g, 47.3 mmol) in degassed DMF/water (3:2, 140 mL) was added [dppf] palladium (II) dichloride (13.0 g, 15.7 mmol). The reaction mixture was flushed with nitrogen, heated at 120° C. for 2 hr and then allowed to cool to RT. The reaction mixture was diluted with EtOAc (500 mL) and aqueous hydrochloric acid (2 M, 500 mL) and the resulting suspension was filtered. The filtrate was extracted with aqueous hydrochloric acid (2 M, 2500 mL). The combined aqueous extracts were basified with a saturated aq solution of sodium carbonate to pH 10. The precipitate formed was filtered and the filtrate was extracted with EtOAc (31 L). The combined organic extracts were dried, filtered and the solvent removed in vacuo to afford a grey solid. All solid materials generated during the workup procedure were combined and triturated with DCM to afford 3-(4-amino-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenol (2) (6.04 g, 84%) as a grey solid: m/z 228 (M+H)+ (ES+).
84%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate In water; N,N-dimethyl-formamide at 120℃; for 2h; Inert atmosphere;	1 3- (3-(tert-Butyldimethylsilyloxy)phenyl)-1H^yrazolo[3,4-d]pyrimidin-4-amine (6) To a stirred suspension of 3-iodo-1 /-/-pyrazolo[3,4-c]pyrimidin-4-amine (3) (8.22 g, 31.5 mmol), 3-phenol boronic acid (13.0 g, 94.5 mmol) and potassium phosphate (10.0 g, 47.3 mmol) in degassed DMF/water (3:2, 140 mL) was added Pd(dppf)CI2(13.0 g, 15.7 mmol). The reaction mixture was flushed with nitrogen, heated at 120 C for 2 hr and then allowed to cool to RT. The reaction mixture was diluted with EtOAc (500 mL) and hydrochloric acid (2 M, 500 mL) and the resulting suspension was filtered. The filtrate was extracted with hydrochloric acid (2 M, 2 x 500 mL). The combined aqueous extracts were basified with a saturated aqueous solution of sodium carbonate to pH 10. The precipitate formed was filtered and the filtrate was extracted with EtOAc (3 x 1 L). The combined organic extracts were dried, filtered and the solvent removed in vacuo to afford a grey solid. All solid materials generated during the workup procedure were combined and triturated with DCM to afford 3-(4-amino-1 /-/-pyrazolo[3,4-c]pyrimidin-3-yl)phenol (5) (6.04 g, 84%) as a grey solid: m/z 228 (M+H)+(ES+).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2011/48111, 2011, A1 Location in patent: Page/Page column 42
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - US2012/208799, 2012, A1 Location in patent: Page/Page column 19
[3]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2013/136075, 2013, A1 Location in patent: Page/Page column 20

41
[ 87199-18-6 ]
[ 612-76-0 ]
[ 108-46-3 ]

Reference： [1]European Journal of Inorganic Chemistry,2011,p. 3232 - 3239

42
[ 81971-39-3 ]
[ 87199-18-6 ]
[ 1349798-36-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7076 - 7080

43
[ 117719-17-2 ]
[ 87199-18-6 ]
[ 1252598-09-6 ]

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 1082 - 1084

44
[ 117718-74-8 ]
[ 87199-18-6 ]
[ 1252594-43-6 ]

Yield	Reaction Conditions	Operation in experiment
68%	With sodium carbonate In 1,2-dimethoxyethane at 130℃; for 0.05h; Microwave irradiation;	B1 Preparation of Final Product 2-01 A mixture of intermediate I-12 (100 mg, 0.282 mmol), 3-hydroxyphenylboronic acid (85 mg, 0.685 mmol), and PdCl2(dppf).DCM (23 mg. 0.028 mmol) in DME (1.2 mL) was added a saturated aqueous solution of sodium carbonate (1 mL). The mixture was heated to 130° C. under microwave irradiation for 3 min. The reaction mixture was cooled, diluted with chloroform, washed with brine. The organic phase was dried (Na2SO4), filtered and the solvent removed in vacuo. The residue was purifired by biotage chromatography with a gradient cyclohexane/EtOAc: from 100% to 50:50. The desired fractions were collected and the solvent evaporated. The resulting solid was crystallised with MeOH to obtain a white solid as final product 2-01 (44 mg, Y: 68% yield).
68%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate In 1,2-dimethoxyethane; water at 130℃; for 0.05h; Microwave irradiation;	B1 Preparation of Final Product 2-01 A mixture of intermediate 1-12 (100 mg, 0.282 mmol), 3-hydroxyphenylboronic acid (85 mg, 0.685 mmol), and PdC12(dppf)DCM (23 mg. 0.028 mmol) in DME (1.2 mE) was added a saturated aqueous solution of sodium carbonate (1 mE). The mixture was heated to 130° C. under microwave irradiation for 3 mm. The reaction mixture was cooled, diluted with chloroform, washed with brine. The organic phase was dried (Na2SO4), filtered and the solvent removed in vacuo. The residue was purified by biotage chromatography with a gradient cyclohexane/EtOAc: from 100% to 50:50. The desired fractions were collected and the solvent evaporated. The resulting solid was crystallised with MeOR to obtain a white solid as final product 2-01 (44 mg, Y: 68%yield).

Reference： [1]Current Patent Assignee: SPANISH NATIONAL CANCER RESEARCH CENTER - US2012/83492, 2012, A1 Location in patent: Page/Page column 99
[2]Current Patent Assignee: SPANISH NATIONAL CANCER RESEARCH CENTER - US9993554, 2018, B2 Location in patent: Page/Page column 255

45
[ 659731-48-3 ]
[ 87199-18-6 ]
[ 1377697-97-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,2-dimethoxyethane; ethanol; at 100℃; for 2h;	To <strong>[659731-48-3]5-chloro-2-fluoro-4-iodopyridine</strong> (516 mg, 2.004 mmol) add 3- hydroxyphenylboronic acid (498 mg, 3.61 mmol), PdC12(dppf).CH2C12 adduct (164 mg, 0.200 mmol), DME (12.5 ml), Ethanol (1.5 ml) and last add 2M sodium carbonate (3.51 ml, 7.02 mmol). The reaction was stirred at 100 C for 2 hr and followed by LCMS. The reaction was cooled, 200 ml of ethyl acetate was added, and washed with saturated sodium bicarbonate, water, saturated salt solution, dried sodium sulfate, filtered and concentrated to crude product. The crude was purified by silica gel chromatography using 40g column eluting with 0%-35% ethyl acetate with hexane. The desired fractions were concentrated to constant mass, giving 425 mg of the titled compound as free base used without further purification. LCMS (m/z): 224.1 (MH+), rt = 0.85 min.

Reference： [1]Patent: WO2012/66065,2012,A1 .Location in patent: Page/Page column 110

46
[ 87199-18-6 ]
[ 871231-45-7 ]

Reference： [1]Journal of the American Chemical Society,2012,vol. 134,p. 11667 - 11673
[2]Organic Letters,2012,vol. 14,p. 4814 - 4817,4

47
[ 97165-77-0 ]
[ 87199-18-6 ]
5-bromo-3'-hydroxybiphenyl-3-carbonitrile [ No CAS ]
C₁₉H₁₃NO₂ [ No CAS ]

Reference： [1]Chemical Biology and Drug Design,2012,vol. 80,p. 775 - 780,6

48
[ 51628-12-7 ]
[ 87199-18-6 ]
[ 1443159-80-5 ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); potassium bromide; In 1,4-dioxane; at 85℃;Inert atmosphere;	General procedure: A stirred mixture of <strong>[51628-12-7]4-iodophenylacetonitrile</strong> (35), arylboronic acid (36-45) (1.1 equiv), Pd(PPh3)4 (0.03 equiv), KBr (1.1 equiv), and K3PO4 (2.5 equiv) in dioxane (5 mL/mmol) was purged with N2 for10 min at room temperature and then stirred overnight at 85 C under N2. The mixture was diluted with water and extracted with AcOEt. The organic phase was washed three times with water, dried (Na2SO4), and evaporated under vacuum. The residue was chromatographedon silica gel.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 63,p. 118 - 132

49
[ 87199-18-6 ]
[ 16234-15-4 ]
3-(4-morpholinothieno[3,2-d]pyrimidin-2-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 6h;Inert atmosphere;	General procedure: A mixture of 4 (1.5g, 5.9mmol), 4-hydroxyphenyl boronic acid (1.4g, 9.9mmol), K2CO3 (1.2g, 8.8mmol), Pd (PPh3)4 (0.2g, 0.2mmol) and DMF (20mL) was heated at 85C under nitrogen. After 6h, the reaction was was poured to H2O (30mL) and extracted with ethyl acetate. The combined organic was washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated under vacuum. The residue was recrystallized from ethanol to give a yellowed solid 5a. Yield 80%.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 358 - 365

50
[ 626-02-8 ]
[ 87199-18-6 ]
[ 612-76-0 ]

Reference： [1]Journal of Organic Chemistry,2014,vol. 79,p. 4104 - 4118
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 2648 - 2659
[3]Frontiers in Immunology,2020,vol. 11

51
[ 87199-18-6 ]
[ 436799-32-5 ]
3-[6-(trifluoromethyl)pyridin-3-yl]phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86.6%	With potassium phosphate; palladium diacetate; In tetrahydrofuran; water; for 6h;Reflux;	3-hydroxyphenyl boronic acid (formula 48-A, 12 mmol, 1.66 g), 2-bromo-5-trifluoromethyl-pyridine (formula 48-B, 10 mmol, 2.26 g), potassium phosphate (25 mmol, 5.33 g), palladium acetate (0.1 mmol, 23 mg), THF (50 ml) and water (50 ml) were successively added to a 250 ml, three-necked reaction flask, heated to reflux temperature to react for 6 hours. When the reaction was finished, THF was removed by rotary evaporation and ethyl acetate (40 ml×3) was added for extraction, dried, filtered, desolventized, crystallized and dried to obtain 2.10 g of pale yellow solid, i.e. compound of formula 48-C, with the content of 98.2% (HPLC) and the yield of 86.6%.

Reference： [1]Patent: US2017/1961,2017,A1 .Location in patent: Paragraph 0034; 0035
[2]Molecular Crystals and Liquid Crystals,2015,vol. 607,p. 264 - 271

52
[ 118-72-9 ]
[ 87199-18-6 ]
3-((2,6-dimethylphenyl)thio)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With copper diacetate; triethylamine; In dichloromethane; at 0 - 5℃; for 4h;Sonication; Green chemistry;	General procedure: Naphthylboronic acid (0.25 g, 1.5 mmol) was added with 0.094 g of phenol (1.0 mmol) to 15 mL of DCM. Copper(II) acetate (0.36 g, 2.0 mmol) was then added along with triethylamine (0.5g, 5.0 mmol), and the dismembrator horn placed in the reaction vessel. The sonicator was set to 55 watts and the reaction was allowed to proceed for 4 hours (1 minute pulse with a 3 second rest). Post reaction, the product was isolated by column chromatography. Product yields were determined by weight and purity was confirmed by GC/MS and NMR.

Reference： [1]Heterocycles,2015,vol. 90,p. 271 - 297

53
[ 1532-71-4 ]
[ 87199-18-6 ]
[ 134948-98-4 ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 6766 - 6769

54
[ 4295-11-8 ]
[ 87199-18-6 ]
3-(6-methylquinolin-2-yl)phenol [ No CAS ]

Reference： [1]RSC Advances,2015,vol. 5,p. 77948 - 77957

55
[ 87199-18-6 ]
[ 203436-45-7 ]
3-(2-chloro-9-isopropyl-9H-purin-6-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 70℃; for 5h;Inert atmosphere;	Step 1: synthesis of 3-(2-chloro-9-isopropyl-9H-purin-6-yl)phenol (5a)To a pre-stirred of solution of <strong>[203436-45-7]2,6-dichloro-9-isopropyl-9H-purine</strong> 3a (230 mg, 1.0 mmol), (3- hydroxyphenyl)boronic acid 4c (152 mg, 1.1 mmol) in dioxane (10 mL), were added a solution of K2C03 (345 mg, 2.5 mmol) in deionized water (1.0 mL). The mixture was degassed for 30 mm then added Pd(dppf)C12.CH2C12 (41 mg), and the resulting mixture was heated at 70C for 5 hours. LC-MS showed the reaction completed. After a simple workup, the product 5a (215 mg, 75%) was obtained by flash chromatography (silica, 20% to 50% ethyl acetate in hexanes).
75%		To a pre-stirred of solution of 2,6-dichloro-9-isopropyl-9Hpurine13a (230 mg, 1.0 mmol), (3-hydroxyphenyl)boronic acid 14a(152 mg, 1.1 mmol) in dioxane (10 mL), were added a solution of K2CO3 (345 mg, 2.5 mmol) in deionized water (1.0 mL). The mixturewas degassed for 30 min then added Pd(dppf)Cl2·CH2Cl2 (41 mg), andthe resulting mixture was heated at 70 C for 5 h. LC-MS showed the reaction completed. After a simple workup, the product 15a (215 mg,75%) was obtained by flash chromatography (silica, 20% to 50% ethylacetate in hexanes). LC-MS m/z (relative intensity): [M + H]+ 289.3(100%), 291.3 (33.5%). 1H NMR (400 MHz, CDCl3) δ 8.33 (dt, J = 7.8and 1.2 Hz, 1H), 8.24 (dd, J = 2.5 and 1.6 Hz, 1H), 8.18 (s, 1H), 7.43(t, J = 8.0 Hz, 1H), 7.04 (ddd, J = 8.1, 2.6, and 0.9 Hz, 1H), 5.92 (s,1H), 4.97 (septet, J = 6.8 Hz, 1H), 1.66 (d, J = 6.8 Hz, 6H).

Reference： [1]Patent: WO2015/137887,2015,A1 .Location in patent: Page/Page column 62; 63
[2]Bioorganic Chemistry,2020,vol. 98

56
[ 452-79-9 ]
[ 87199-18-6 ]
3-(2-fluoro-4-methylphenyl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With palladium diacetate; potassium carbonate; In 2-methoxy-ethanol; water; at 20℃; for 15h;	General procedure: To a solution of the corresponding boronic acid (1.2mmol) in EGME/H2O (3:1, 0.25M) were added Pd(OAc)2 (0.05mmol) and K2CO3 (1.2mmol), followed by the addition of the corresponding phenyl iodide (1.0mmol). The dark reaction mixture was stirred at rt for 15h, then diluted with EtOAc (40mL) and filtered through a pad of Celite. The resulting filtrate was washed with H2O (20mL) and a 1M solution of Na2SO3 (20mL). After separation, the organic phase was dried over Na2SO4 and concentrated under reduced pressure. The residues were purified by column chromatography (Cy/EtOAc).

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 109,p. 216 - 237

57
[ 452-79-9 ]
[ 87199-18-6 ]
[3-(2-fluoro-4-methylphenyl)phenyl] N-hexylcarbamate [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 109,p. 216 - 237

58
[ 68162-47-0 ]
[ 87199-18-6 ]
C₁₃H₁₄B₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In tetrahydrofuran; N,N-dimethyl-formamide; at 20℃;	3-Hydroxyphenylboronic acid (40 mg, 1.05 equiv) and 4-(bromomethyl)phenylboronic acid (65 mg, 1.0 equiv) were dissolved in 6 mE solution of tetrahydrothranN,Ndimethylforamide (1:1 v/v). Sodium hydride (36 mg, 5.0 equiv) is added and the reaction is allowed to stir at room temperature overnight. Water (25 mE) is then added and the reaction is acidified to pH<2 with iN HC1 and transferred to a separatory flannel. The water layer is washed with ethyl acetate (1 x75 mE) and diethyl ether (1 x75 mE). The water layer is then concentrated under vacuum to provide crude oil which is triturated with tetrahydrofuran and methanol to provide the desired boronic acid 326. [2M-3H20]=488.0 mlz. Activity: A

Reference： [1]Patent: US2015/368278,2015,A1 .Location in patent: Paragraph 1304; 1305

59
[ 41731-23-1 ]
[ 87199-18-6 ]
3-(5-methyl-1,3-thiazol-2-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 110℃; for 0.5h;Microwave irradiation;	(3-Hydroxyphenyl) boronic acid (170 mg, 1.235 mmol), 2-bromo-5-methyl- l,3-thiazole (200 mg, 1.123 mmol), K3P04 (481 mg, 2.246 mmol) and Pd(Ph3)4 (131 mg, 0.1 12 mmol) in a mixture 3: 1 of dioxane/ water (12 mL : 4 mL) was heated in MW at 1 10 C for 30 min. The mixture was concentrated under vacuum and NaOH aq solution 1 M and DCM were added. The water was extracted several times with more DCM. The layers were separated. To the aqueous phase HC1 1M aqueous solution was added and the phase was extracted again with more DCM. The combined organics were filtered though a phase separator tube and concentrated in vacuo to give the desired product (190 mg, 0.99 mmol, Yield=75%). LC-MS (ESI): mlz (M+l)+, 191.9.

Reference： [1]Patent: WO2016/4272,2016,A1 .Location in patent: Paragraph 00958

60
[ 446273-59-2 ]
[ 87199-18-6 ]
3-(3-amino-6-chloropyridazin-4-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 110℃; for 1.5h;Inert atmosphere;	General procedure: Preparation of 6-chloro-4-arylpyridazin-3-amines Suzuki Method A mixture of sodium carbonate (336 mg, 3.17 mmol),water (5 mL) and 1,4-dioxane (15 mL) were de-gassed with nitrogen for 10 minutesand then treated with the appropriate boronic acid (199 mg, 1.63 mmol) and<strong>[446273-59-2]4-bromo-6-chloropyridazin-3-amine</strong> (330 mg, 1.58 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II),complex with dichloromethane (1:1) (129 mg, 0.16 mmol). The reaction mixturewas heated at 110 Cunder nitrogen for 90 minutes and then cooled to room temperature. The mixturewas partitioned between ethyl acetate and aq brine, the organic layer wasdried, filtered and evaporated under reduced pressure. The crude product waspurified by flash silica chromatography, see below for individual conditions.Fractions containing product were evaporated under reduced pressure to yieldthe desired target.

Reference： [1]Tetrahedron Letters,2015,vol. 56,p. 6791 - 6794

61
[ 3989-13-7 ]
[ 87199-18-6 ]
3'-((trimethylsilyl)ethynyl)-[1,1'-biphenyl]-3-ol [ No CAS ]

Reference： [1]Chinese Chemical Letters,2016,vol. 27,p. 961 - 963

62
[ 166402-16-0 ]
[ 87199-18-6 ]
3-(7-aminoquinoxalin-2-yl)phenol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 6169 - 6186

63
[ 40473-01-6 ]
[ 87199-18-6 ]
3-(3-chloro-6-pyridyl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.4%	With palladium diacetate; cesium fluoride; In ethylene glycol; at -10℃; for 6h;	synthesis of 3-(3-chloro-6-pyridyl)phenol (19-C) The sequentially 1.66g (12mmol) 3-hydroxy-phenylboronic acid (19-A), 1.92g (10mmol) 2-chloro-5-bromo pyridine (19-B), 3.80g (25mmol) cesium fluoride, 45 mg (0.2mmol) palladium acetate, 50 ml of ethylene glycol added to the 250 ml three port in the reaction bottle, controls heats to -10 C reaction 6 hours. After the reaction is complete, add 40 ml × 3 ethyl acetate extraction, with 40 ml × 3 saturated salt water extraction, anhydrous magnesium sulphate drying 2 hours, filtering, desolvation, crystallization, the drying of 1.67g strawcoloured solid, i.e. compound 19-C, content 99.2% (HPLC), the yield is 80.4%.

Reference： [1]Patent: CN103910670,2016,B .Location in patent: Paragraph 0062; 0063; 0064

64
[ 87199-18-6 ]
[ 98-88-4 ]
[ 6949-73-1 ]

Reference： [1]ChemCatChem,2016,vol. 8,p. 3207 - 3212

65
[ 13195-50-1 ]
[ 87199-18-6 ]
3-(5-nitrothiophen-2-yl)phenol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 8830 - 8847

66
[ 108-86-1 ]
[ 87199-18-6 ]
[ 580-51-8 ]

Yield	Reaction Conditions	Operation in experiment
81%	With potassium carbonate; In water; at 70℃; for 0.5h;Inert atmosphere;	General procedure: In a typical run, h-BN(at)Fur(at)Pd(OAc)2 (0.05 mmol) was added to a mixture of arylboronic acid 1 (1.0 mmol), aryl bromide 2 (1.5 mmol) and K2CO3 (1.5 mmol) in water (1 mL). The resulting mixture was stirred at 70 C under Ar protection, and the progress of the reaction was monitored by TLC. After completion of the reaction, ethyl acetate was added to the reaction mixture and the catalyst was separated. The organic phase was washed with water, dried over anhydrous Na2SO4 and the solvent was evaporated under reduced pressure. Finally, the residue was isolated by chromatography on a column of silica gel to afford the corresponding product 3.

Reference： [1]Advanced Synthesis and Catalysis,2017,vol. 359,p. 454 - 466
[2]Applied Organometallic Chemistry,2017,vol. 31
[3]Tetrahedron,2016,vol. 72,p. 8557 - 8564

67
[ 87199-18-6 ]
[ 175205-82-0 ]
3-(3-trifluoromethyl-2-pyridyl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.6%	With palladium diacetate; potassium carbonate; In 1,4-dioxane; water; for 6h;Reflux;	3-hydroxyphenyl boronic acid (formula 86-A, 12 mmol, 1.66 g), 2-bromo-5-trifluoromethyl-pyridine (formula 86-B, 10 mmol, 2.26 g), potassium carbonate (25 mmol, 3.45 g), palladium acetate (0.5 mmol, 110 mg), dioxane (50 ml) and water (50 ml) were successively added to a 250 ml, three-necked reaction flask, heated for reflux temperature to react for 6 hours. When the reaction was finished, dioxane was removed by rotary evaporation and ethyl acetate (40 ml×3) was added for extraction, the organic phase was dried, filtered, desolventized, crystallized and dried to obtain 1.94 g of pale yellow solid, i.e. compound of formula 86-C, with the content of 99.1% (HPLC) and the yield of 80.6%.

Reference： [1]Patent: US2017/1961,2017,A1 .Location in patent: Paragraph 0038; 0039

68
[ 87199-18-6 ]
[ 175205-81-9 ]
3-(4-trifluoromethyl-2-pyridyl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85.5%	With palladium diacetate; cesium fluoride; In toluene; at 25℃; for 6h;	3-hydroxyphenyl boronic acid (formula 87-A, 12 mmol, 1.66 g), 2-bromo-5-trifluoromethyl-pyridine (formula 87-B, 10 mmol, 2.26 g), cesium fluoride (25 mmol, 3.80 g), palladium acetate (0.2 mmol, 45 mg), toluene (50 ml) were successively added to a 25 ml, three-necked reaction flask to react at room temperature (25° C.) for 6 hours. When the reaction was finished, the solution was extracted with ethyl acetate (40 ml×3) and water (40 ml), the organic phase was dried, filtered, desolventized, crystallized and dried to obtain 2.09 g of pale yellow solid, i.e. compound of formula 87-C, with the content of 97.8percent (HPLC) and the yield of 85.5percent.

Reference： [1]Patent: US2017/1961,2017,A1 .Location in patent: Paragraph 0042; 0043

69
[ 87199-18-6 ]
[ 175205-81-9 ]
C₂₃H₁₉F₃N₂O₄ [ No CAS ]

Reference： [1]Patent: US2017/1961,2017,A1

70
[ 22960-18-5 ]
[ 87199-18-6 ]
3-(6-fluoroquinolin-8-yl)phenol [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 9996 - 10000

71
[ 917251-92-4 ]
[ 87199-18-6 ]
3-(5-(trifluoromethyl)quinolin-8-yl)phenol [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 9996 - 10000

72
[ 139366-35-1 ]
[ 87199-18-6 ]
3-(5-nitroquinolin-8-yl)phenol [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 9996 - 10000

73
[ 14482-51-0 ]
[ 87199-18-6 ]
C₂₂H₁₈Cl₂N₂O₄ [ No CAS ]

Reference： [1]Journal of Agricultural and Food Chemistry,2017,vol. 65,p. 6114 - 6121

74
[ 14482-51-0 ]
[ 87199-18-6 ]
C₁₁H₇Cl₂NO [ No CAS ]

Reference： [1]Journal of Agricultural and Food Chemistry,2017,vol. 65,p. 6114 - 6121

75
[ 87199-18-6 ]
[ 162102-79-6 ]
C₁₅H₁₃NO₅ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 7267 - 7283

76
[ 585-76-2 ]
[ 87199-18-6 ]
[ 171047-01-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate; In 1,4-dioxane; water; at 95.0℃;Inert atmosphere;	General procedure: The halo aryl (1.0 equiv) was dissolved in a mixture of water:dioxane (1:1). The boronic acid or ester(1.5 equiv) and potassium phosphate (5.0 equiv) were added. The solution was degassed byvacuum/argon cycles (10 times) before addition of PdCl2(PPh3)2 (10 mol%) and further degassed (5times). The resulting mixture was stirred at 95 C under argon atmosphere for 16-20 hours. Thereaction mixture was filtered through Celite and diluted with water (approx. 30 mL) before washingwith chloroform (3 x 30 mL). If not stated otherwise, the aqueous phase was concentrated underreduced pressure and applied to a C18 precolumn before purification on a 10g or 60 g C18 column witha gradient of acetonitrile in water (10-100%) to yield the desired product.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 145,p. 634 - 648

77
[ 69518-17-8 ]
[ 87199-18-6 ]
C₁₄H₈N₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%		Pd(PPh3)4 (45mg, OM39mmol) was added to a solution of <strong>[69518-17-8]4-iodo-phthalonitrile</strong>(lg, 3.937mmo1) in dry THF (35mL) and the reaction mixture was stirred for 20 minutes.K2C03 (544 mg, 3.937 rnmol), 3hydroxyphenylboronic acid (543 mg, 3.937 mmol) andH20 (10 mL) were added and the reaction mixture refluxed for 24 hours, after which itwas cooled to room temperature. The THF was evaporated and the resulting solidsuspended in H20 was filtered, washed with H20, redissolved in THF and dried over Na2504. After evaporation of the solvent the solid was purified by column chromatography on silica gel, using heptane/EtOAc 2:1 as eluent, yielding 1 (0.867g, 1 ,338mmo1, 34%) as a white solid.1H NMR (300 MHz, CDC13), oe (ppm): 7.98 (p, J = 9.3 Hz, 1H, H1), 7.93 - 7,83 (m,2H, H), 7.38 (d, J = 7.5 Hz, 1H, H1), 7.14 (d, J = 8.5 Hz, 1H, H), 7.05 (s, 1H, H),6.95 (d, J = 9.5 Hz, 1H, H), 4.93 (s, 1H, OH).13 NMR (300 MHz, MCOD), 6 (ppm): 141.48, 136.46, 134.14, 131.77, 123.63, 98.96.HRMS (MALDITOF, DCTB), in/z: Caic. for C14H8N2ONa: 243.0528, found 243.0524 [M+Na]

Reference： [1]Patent: WO2018/2170,2018,A1 .Location in patent: Page/Page column 32; 33

78
[ 87199-18-6 ]
[ 16097-63-5 ]
3-(2-(methylthio)-6-(trifluoromethyl)pyrimidin-4-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 110℃; for 5.0h;Inert atmosphere;	To a solution of 4-chloro-2- (methylthio) -6- (trifluoromethyl) pyrimidine (200mg, 0.87mmol) and (3-hydroxyphenyl) boronic acid (150mg, 1.05mmol) in DME/H2O (5mL/1mL) was added Pd (dppf) 2Cl2 (32mg, 0.04mmol) followed by Na2CO3 (280mg, 2.62mmol) under N2 atmosphere. The reaction mixture was refluxed at 110 for 5hrs. The reaction mixture was cooled to room temperature and filtered over celite. Solvents were removed in vacuo, and the residue was extracted by DCM and H2O 3 times. The organic layer was combined, washed with brine, dried over Na2SO4 and further purified by silica gel column chromatography (PE/EA30/1) to give 104mg of 3- (2- (methylthio) -6- (trifluoromethyl) pyrimidin-4-yl) phenol (71-01) as a white solid (41)

Reference： [1]Patent: WO2018/14802,2018,A1 .Location in patent: Paragraph 0277

79
[ 87199-18-6 ]
[ 405224-23-9 ]
C₁₂H₇ClN₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In methanol; water; toluene;Inert atmosphere;	General procedure: <strong>[405224-23-9]5-bromo-2-chloronicotinonitrile</strong> (5, 2.16 g, 10 mmol), aromatic boronic acid (10 mmol), (PPh3)2PdCl2 (175 mg, 0.25 mmol), Na2CO3 (2.12 g, 20 mmol) were dissolved in a mixed solvent (22 mL, toluene: ethanol: water = 10: 10: 2). Nitrogen gas was bubbled through the reaction mixture for 5 min, and then the mixture was heated to 60C under inert atmosphere for 6 h. The mixture was filtered and the filtrate was concentrated under vacuum. The crude product was extracted with ethyl acetate and the organic layer was concentrated, then the solid was washed with ethyl acetate and petroleum ether to give compounds 6.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 1386 - 1391

80
[ 5941-55-9 ]
[ 87199-18-6 ]
ethyl 3-(3-hydroxyphenyl)-3-ethoxypropanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With chloro(1,5-cyclooctadiene)rhodium(I) dimer; potassium hydroxide; In 1,4-dioxane; water; at 50℃; for 2h;Inert atmosphere; Sealed tube;	A mixture of (E)-<strong>[5941-55-9]ethyl 3-ethoxyacrylate</strong> (0.600 mL, 4.00 mmol), 3-hydroxyphenyl boronic acid (1.70 g, 12.0 mmol), Rh(COD)Ch (102 mg, 0.207 mmol) and potassium hydroxide (234 mg, 4.17 mmol) in 1,4-dioxane (5 mL) and water (0.5 mL) was stirred for 2 h under a nitrogen atmosphere at 50 C in a sealed tube. The reaction mixture was allowed to cool to RT and poured into 50 mL of saturated aq. H4CI, followed by extraction with ethyl acetate (3 x 50 mL). The organic layers were combined, dried over Na2S04 and concentrated. The residue obtained was purified on silica gel with ethyl acetate/petroleum ether (0-10%) to give compound 24a. Mass Spectrum (LCMS, ESI pos.): Calcd. For CisHieCU: 237.1 [M-H]+; found: 237.1.

Reference： [1]Patent: WO2018/81047,2018,A1 .Location in patent: Page/Page column 123-124

81
[ 21014-26-6 ]
[ 87199-18-6 ]
(S)-ethyl 3-cyclopropyl-3-(3-hydroxyphenyl)propanoate [ No CAS ]
(R)-ethyl 3-cyclopropyl-3-(3-hydroxyphenyl)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With chloro(1,5-cyclooctadiene)rhodium(I) dimer; sodium hydroxide In 1,4-dioxane at 50℃; for 16h; Inert atmosphere;	36.E (E) Ethyl (,S)-3-cyclopropyl-3-(3-hydroxyphenyl)propanoate, (36e-l) and ethyl (R)-3- cyclopropyl-3-(3-hydroxyphenyl)propanoate, (36e-2) To a solution of chloro(l,5-cyclooctadiene)rhodium (I) dimer (2.46 g, 4.99 mmol) in 1,4-dioxane (50 mL) was added NaOH (aq. IN, 150 mL, 150 mmol) at RT under a nitrogen atmosphere. (3-Hydroxyphenyl)boronic acid (27.6 g, 200 mmol) was added, followed by the addition of ethyl (E)-3-cyclopropylacrylate, cpd 36d (14 g, 100 mmol) in 1,4-dioxane (50 mL). The mixture was stirred at 50 °C for 16 h. The mixture was poured into ethyl acetate/water and acidified with 2N HC1 to pH~4. The aqueous layer was extracted with ethyl acetate (2x). The combined organic layers were dried (Na2S04), filtered and concentrated. The resulting residue was first purified by flash chromatography on silica gel with EtO Ac/heptane (0-30%) to give a yellow oil, which was further purified by chiral SFC on a Chiralcel OD-H 5μιη column (250 x 30mm) using 93% CO2, 7% i- PrOH to afford compounds 36e-l ([CX]D20= +35.7 ) and 36e-2. Cpd 36e-2 : 1H NMR (CDCh) δ (ppm): 7.17 (t, J=7.8 Hz, 1H), 6.81 (d, J=7.6 Hz, 1H), 6.72 (t, J=2.0 Hz, 1H), 6.67-6.71 (m, 1H), 4.98 (s, 1H), 4.07 (qd, J=7.1, 3.5 Hz, 2H), 2.66-2.79 (m, 2H), 2.32 (dt, J=9.6, 7.6 Hz, 1H), 1.18 (t, J=7.3 Hz, 3H), 0.95-1.06 (m, 1H), 0.54-0.62 (m, 1H), 0.39-0.48 (m, 1H), 0.27 (dq, J=9.5, 4.7 Hz, 1H), 0.12-0.19 (m, 1H).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2018/81047, 2018, A1 Location in patent: Page/Page column 153

82
[ 850832-54-1 ]
[ 87199-18-6 ]
methyl 4-(3-hydroxyphenyl)-5-methylisoxazole-3-carboxylate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 8337 - 8352

83
[ 87199-18-6 ]
[ 139308-52-4 ]
C₁₃H₁₄N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27.3%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; water; at 70℃; for 6h;	To a solution of compound 142B (3.4 g, 14.59 mmol) and (3- hydroxyphenyl)boronic acid (2.41 g, 17.51 mmol) in dioxane/H20 (50 mL/10 mL) was added K3PO4 (9.29 g, 43.77 mmol) and Pd(dppf)Cl2 (1.07 g, 1.46 mmol). The mixture was stirred at 70 C for 6 h. The reaction mixture was concentrated under reduced pressure to remove solvent. The residue was diluted with H20 (80 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine (50 mL x 2), dried over Na2S04, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate = 10/1 to 7: 1) to give the Compound 142C (1.0 g, yield: 27.3%) was obtained as a yellow solid. 1H NMR (400MHz, CDC13) delta 8.01 - 7.87 (m, 1H), 7.36 - 7.32 (m, 1H), 7.30 - 7.26 (m, 2H), 6.90 - 6.79 (m, 1H), 5.41 - 5.30 (m, 1H), 4.24 (q, J=7.1 Hz, 2H), 3.94 (s, 3H), 1.28 (t, J=7.2 Hz, 3H). MS (ESI) m/z (M+H)+ 247.0.

Reference： [1]Patent: WO2018/9417,2018,A1 .Location in patent: Paragraph 0576

84
[ 87199-18-6 ]
[ 4027-57-0 ]
C₁₃H₁₄N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25.04%	With pyridine; oxygen; copper diacetate; In dichloromethane; at 28℃; under 775.743 Torr; for 48h;Molecular sieve;	To a solution of ethyl 3-methyl-lH-pyrazole-5-carboxylate (20 g, 129.73 mmol), (3-hydroxyphenyl)boronic acid (27 g, 194.59 mmol), 4A MS (30 g) and Py (12 mL, 142.70 mmol) in DCM (500 mL) was added Cu(OAc)2 (26 g, 142.70 mmol). After addition, the reaction mixture was stirred at 28 C for 48h under 02 (15 psi) atmosphere. 100 mL of DCM was added into the reaction mixture and the mixture was filtered. The filtrate was concentrated in vacuum and the residue was dissolved into 300 mL of EtOAc. The mixture was filtered and the filtrate was concentrated in vacuum. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate = 5/1 to 4: 1 to 3/1) to afford compound 3 (8.0 g, yield 25.04%) as light yellow solid. 1H NMR (400MHz, DMSO-d6) delta 7.21 (t, J=7.9 Hz, 1H), 6.85 - 6.69 (m, 4H), 4.15 (q, J=7.1 Hz, 2H), 2.23 (s, 3H), 1.16 - 1.12 (m, 3H). MS (ESI) m/z (M +H)+ 246.9.

Reference： [1]Patent: WO2018/9417,2018,A1 .Location in patent: Paragraph 0569

85
[ 156682-54-1 ]
[ 87199-18-6 ]

Yield	Reaction Conditions	Operation in experiment
84%	With palladium 10% on activated carbon; hydrogen In ethyl acetate at 30 - 35℃; for 8h;	2 Under the protection of nitrogen, add 24.9g (0.095mol) of the above solid to 80mL of tetrahydrofuran, and dissolve completely under stirring,After cooling to -10 ° C to 0 ° C, 1.3M isopropylmagnesium chloride-lithium chloride / tetrahydrofuran solution (94mL, 0.122mol) was added dropwise. After the addition was completed, the heat exchange reaction was continued for 1 hour.After the reaction was completed, the above solution was added dropwise to a solution (50 mL) of trimethyl borate (14.7 g, 0.141 mol) dissolved in tetrahydrofuran,After the dropwise addition was completed, the heat preservation was continued to stir for 5 hours, and then it was naturally raised to room temperature and stirred to react overnight.Add 10% hydrochloric acid to quench, adjust pH = 3-4, extract twice with ethyl acetate, and wash with saturated brine.The ethyl acetate layer (containing 19.5g of product in the external calibration solution) was transferred to the hydrogenation reactor,Add 0.8 grams of 10% wet palladium carbon, heat to 30-35 , fill with hydrogen pressure 0.3MPa, stir the reaction for 8 hours,After the reaction is completed, the palladium carbon is filtered off (for reuse), the filtrate is distilled under reduced pressure, and the crude product is slurried with acetone and heptane,12.44 g of white solid was obtained, the total yield in two steps was 84%, and the purity of HPLC was 99.7%.

Reference： [1]Current Patent Assignee: CANGZHOU PURUIDONGFANG TECH - CN111072698, 2020, A Location in patent: Paragraph 0026-0027; 0029

86
[ 50-00-0 ]
[ 87199-18-6 ]
[ 1196473-37-6 ]

Yield	Reaction Conditions	Operation in experiment
25%	With trifluoroacetic acid; In chloroform; at 40℃; for 20h;Schlenk technique; Inert atmosphere; Sealed tube;	Into the Schlenk tube, add the stirring magnet, the compound 1m (138mg, 1mmol) of the above formula, and the paraformaldehyde 2 (36mg, 1.2mmol) in sequence,Under nitrogen protection, trichloromethane (10 mL) was added, and trifluoroacetic acid (297 μL, 4 mmol) was added with stirring, and then sealed, heated and stirred at 40 C for reaction for 20 hours. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography to obtain the compound of formula 3m (37 mg, 25%).

Reference： [1]Patent: CN112625056,2021,A .Location in patent: Paragraph 0092-0095

87
[ 87199-18-6 ]
[ 612-76-0 ]

Reference： [1]Organic Letters,2021,vol. 23,p. 2873 - 2877

88
[ 936-08-3 ]
[ 87199-18-6 ]
5-chloro-3'-hydroxy-[1,1'-biphenyl]-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	Stage #1: 2-bromo-4-chlorobenzoic acid; 3-hydroxyphenylboronic acid With palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride; anhydrous sodium carbonate In toluene for 14h; Inert atmosphere; Stage #2: With sodium hydroxide In tetrahydrofuran; methanol; water monomer at 20℃;

Reference： [1]Luo, Dan; Hu, Liangzhen; Gao, Tianyong; Zhang, Xiaohui; Xiong, Yan [Journal of Organic Chemistry, 2022, vol. 87, # 8, p. 5065 - 5075]

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P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

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

[ CAS No. 87199-18-6 ] {[proInfo.proName]}

Quality Control of [ 87199-18-6 ]

Related Doc. of [ 87199-18-6 ]

Product Details of [ 87199-18-6 ]

Calculated chemistry of [ 87199-18-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 87199-18-6 ]

Application In Synthesis of [ 87199-18-6 ]

[ 87199-18-6 ] Synthesis Path-Upstream 1~9

[ 87199-18-6 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 87199-18-6 ]

Organoboron

Aryls

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 87199-18-6 ]