[ CAS No. 173194-95-1 ] {[proInfo.proName]}

Name: 173194-95-1|(6-Hydroxynaphthalen-2-yl)boronic acid|98%
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Quality Control of [ 173194-95-1 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 173194-95-1 ]

Product Details of [ 173194-95-1 ]

CAS No. :	173194-95-1	MDL No. :	MFCD00092986
Formula :	C₁₀H₉BO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SNJANQMHRGSHFN-UHFFFAOYSA-N
M.W :	187.99	Pubchem ID :	4349738
Synonyms :

Calculated chemistry of [ 173194-95-1 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	3.0
Molar Refractivity :	55.8
TPSA :	60.69 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.23 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.72
Log Po/w (WLOGP) :	0.23
Log Po/w (MLOGP) :	0.73
Log Po/w (SILICOS-IT) :	-0.16
Consensus Log Po/w :	0.5

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.55
Solubility :	0.528 mg/ml ; 0.00281 mol/l
Class :	Soluble
Log S (Ali) :	-2.61
Solubility :	0.461 mg/ml ; 0.00245 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.39
Solubility :	0.764 mg/ml ; 0.00406 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.57

Safety of [ 173194-95-1 ]

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

Application In Synthesis of [ 173194-95-1 ]

* 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 [ 173194-95-1 ]
Downstream synthetic route of [ 173194-95-1 ]

[ 173194-95-1 ] Synthesis Path-Upstream 1~2

1
[ 15231-91-1 ]
[ 173194-95-1 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -70℃; for 2 h; Inert atmosphere Stage #2: With Triisopropyl borate In tetrahydrofuran; hexane at -70 - 20℃; for 3.5 h; Inert atmosphere Stage #3: With hydrogenchloride In tetrahydrofuran; hexane; water at 20℃; for 2 h;	5.58 g (25 mmol) of 6-bromo-2-naphthol was dissolved in 125 ml of dehydrated tetrahydrofuran in an argon atmosphere. After cooling the solution to -70°C, 33 ml (55 mmol) of a hexane solution of n-butyllithium was slowly added dropwise to the solution over 30 minutes. The mixture was stirred at -70°C for 1.5 hours. After the addition of 11.5 ml (50 mmol) of triisopropyl borate, the mixture was stirred at -70°C for 30 minutes. The mixture was then stirred for 3 hours while allowing the mixture to slowly return to room temperature. After the addition of 100 ml of 2 M hydrochloric acid to the reaction mixture, the mixture was stirred at room temperature for 2 hours. The reaction solution was then separated, and the aqueous phase was extracted with ethyl acetate. The organic phase was combined, washed with a saturated sodium chloride solution, and dried with anhydrous sodium sulfate, and the solvent was evaporated. The residue was washed with dichloromethane in a suspended state to obtain 4.02 g of 6-hydroxynaphthalen-2-ylboronic acid (yield: 85percent).
43%	Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1.33333 h; Stage #2: With Triisopropyl borate In tetrahydrofuran; hexane at -78℃; for 0.25 h; Stage #3: With hydrogenchloride In tetrahydrofuran; hexane; water at 0℃; for 0.25 h;	6-Hydroxynaphthalen-2-yI-2-boronic acid (TJA02057) Ci₀H₉BO₃ MW 187.99. A dry 250 ml r.b. flask was loaded with 6-bromo-2-naphthol (5.38 g, 24.1 mmol) and purged with N_2(g>. Anhydrous THF (80 mL) added with stirring and the vessel cooled to -78 ⁰C (dry ice/acetone bath). After 30 mins n-BuLi, 2.3 M in hexanes, (12.9 mL, 28.9 mmol) was added dropwise over 20 min. The reaction was left to stir for 1 h. Triisopropyl borate (6.65 mL, 28.9 mmol) was added dropwise with the reaction still at -78 °C. After 15 min of stirring at this temperature the dry ice/acetone bath was removed. At 0 ⁰C 2 M HCl(_aq) (5 mL) was added and the reaction left to stir for a further 15 min. THF removed under vacuum and residues taken up in distilled water (20 mL) and dichloromethane (50 mL) added. The resulting white precipitate was filtered and washed with dichloromethane and distilled water. Dried under vacuum at 70 ⁰C to give the title compound as an off white solid (1.88 g, 43 percent).¹H NMR (270 MHz₅ DMSCW₆) δ 7.04-7.08 (2H, m, ArH), 7.58-7.61 (IH, d, J= 8.4 Hz, ArH), 7.73-7.76 (2H₅ d, J= 8.4 Hz, ArH)₅ 7.72-7.73 (IH₅ d₅ J= 1.5 Hz₅ ArH)₅ 8.06 (2H₅ S₅ ArB(OH)₂), 8.23 (IH₅ S₅ ArH) and 9.83 (IH₅ S₅ ArOH); HPLC (70 percent CH₃CN in H₂O) t_τ= 5.431 (97.67 percent); LCMS (APCI)₅ m/z 187.04 (M^" - H₅ 100 percent), 142.92 ((M^" - H) - B(OH)₂, 55).

Reference： [1] Patent: EP2597094, 2013, A1, . Location in patent: Paragraph 0093
[2] Patent: WO2007/68905, 2007, A1, . Location in patent: Page/Page column 69-70
[3] Patent: US2004/44258, 2004, A1, . Location in patent: Page 60

2
[ 173194-95-1 ]
[ 1132935-63-7 ]

Reference： [1] Patent: US2012/14913, 2012, A1,

[ 173194-95-1 ] Synthesis Path-Downstream 1~45

1
[ 862730-04-9 ]
[ 173194-95-1 ]
6-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)naphthalen-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; at 80℃;	Synthesis of 6-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)naphthalen-2-ol (BA17); A solution of 6-hydroxynaphthalen-2-yl-2-boronic acid (15 mg, 0.08 mmol) in EtOH (3.3 ml) was added to a solution of <strong>[862730-04-9]3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine</strong> (20 mg, 0.07 mmol) in DME (12 ml). Pd(PPh3)4 (16 mg, 0.014 mmol) and saturated Na2CO3 (1.9 ml) were added and the reaction was heated to 80 C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by RP-HPLC (MeCN:H2O:0.1% TFA) to yield BA15 (4.8 mg, 23% yield). ESI-MS (M+H)+ m/z calcd 320.1, found 320.1.

Reference： [1]Patent: US2007/293516,2007,A1 .Location in patent: Page/Page column 13; 16

2
[ 15231-91-1 ]
[ 173194-95-1 ]

Yield	Reaction Conditions	Operation in experiment
85%		5.58 g (25 mmol) of 6-bromo-2-naphthol was dissolved in 125 ml of dehydrated tetrahydrofuran in an argon atmosphere. After cooling the solution to -70C, 33 ml (55 mmol) of a hexane solution of n-butyllithium was slowly added dropwise to the solution over 30 minutes. The mixture was stirred at -70C for 1.5 hours. After the addition of 11.5 ml (50 mmol) of triisopropyl borate, the mixture was stirred at -70C for 30 minutes. The mixture was then stirred for 3 hours while allowing the mixture to slowly return to room temperature. After the addition of 100 ml of 2 M hydrochloric acid to the reaction mixture, the mixture was stirred at room temperature for 2 hours. The reaction solution was then separated, and the aqueous phase was extracted with ethyl acetate. The organic phase was combined, washed with a saturated sodium chloride solution, and dried with anhydrous sodium sulfate, and the solvent was evaporated. The residue was washed with dichloromethane in a suspended state to obtain 4.02 g of 6-hydroxynaphthalen-2-ylboronic acid (yield: 85%).
43%		6-Hydroxynaphthalen-2-yI-2-boronic acid (TJA02057) Ci0H9BO3 MW 187.99. A dry 250 ml r.b. flask was loaded with 6-bromo-2-naphthol (5.38 g, 24.1 mmol) and purged with N2(g>. Anhydrous THF (80 mL) added with stirring and the vessel cooled to -78 0C (dry ice/acetone bath). After 30 mins n-BuLi, 2.3 M in hexanes, (12.9 mL, 28.9 mmol) was added dropwise over 20 min. The reaction was left to stir for 1 h. Triisopropyl borate (6.65 mL, 28.9 mmol) was added dropwise with the reaction still at -78 C. After 15 min of stirring at this temperature the dry ice/acetone bath was removed. At 0 0C 2 M HCl(aq) (5 mL) was added and the reaction left to stir for a further 15 min. THF removed under vacuum and residues taken up in distilled water (20 mL) and dichloromethane (50 mL) added. The resulting white precipitate was filtered and washed with dichloromethane and distilled water. Dried under vacuum at 70 0C to give the title compound as an off white solid (1.88 g, 43 %).1H NMR (270 MHz5 DMSCW6) delta 7.04-7.08 (2H, m, ArH), 7.58-7.61 (IH, d, J= 8.4 Hz, ArH), 7.73-7.76 (2H5 d, J= 8.4 Hz, ArH)5 7.72-7.73 (IH5 d5 J= 1.5 Hz5 ArH)5 8.06 (2H5 S5 ArB(OH)2), 8.23 (IH5 S5 ArH) and 9.83 (IH5 S5 ArOH); HPLC (70 % CH3CN in H2O) ttau= 5.431 (97.67 %); LCMS (APCI)5 m/z 187.04 (M" - H5 100 %), 142.92 ((M" - H) - B(OH)2, 55).
		Example 1 Synthesis of methyl 3-[4-cyclohexylmethyloxy-3-(6-hydroxynaphthalen-2-yl)-phenyl]Propionate (Compound No. 001) (Preparation Method 4, Step d-1) A solution of 2-bromo-6-hydroxynaphthalene (1.15 g, TCI) in anhydrous THF (50 ml) was cooled to -78 C. under argon atmosphere, added dropwise with 1.6 M solution of n-butyllithium in hexane (6.88 ml, Ald) over 20 minutes and stirred for 30 minutes.The reaction mixture was added dropwise with triisopropyloxyborane (henceforth abbreviated as "(IPrO)3B, 1.73 ml, Ald) over 10 minutes, stirred for 30 minutes, then warmed to room temperature and further stirred for 2 hours.The reaction mixture was added with 0.5 M aqueous sulfuric acid (10 ml) and extracted with diethyl ether (100 ml*3).The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure to obtain crude 6-hydroxy-2-naphthaleneboronic acid (1.85 g).A solution of this product in ethanol (5.0 ml), Intermediate 7 (1.16 g) and 2 M aqueous sodium carbonate (12.0 ml) were added with toluene (10.0 ml) and tetrakistriphenylphosphine palladium (0) (henceforth abbreviated as "(Ph3P)4Pd", 570 mg, Nacalai Tesque) and stirred at 100 C. for 25 hours.The reaction mixture was added with ethyl acetate (300 ml) and washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine.The organic layer was dried, and then the solvent was evaporated under reduced pressure.The residue was purified by flash column chromatography (hexane:ethyl acetate=6:1) to obtain the title compound (Compound No. 001, 1.04 g).

Reference： [1]Patent: EP2597094,2013,A1 .Location in patent: Paragraph 0093
[2]Patent: WO2007/68905,2007,A1 .Location in patent: Page/Page column 69-70
[3]Patent: US2004/44258,2004,A1 .Location in patent: Page 60

3
methyl (3-bromo-4-cyclohexylmethyloxyphenyl)propionate [ No CAS ]
[ 173194-95-1 ]
[ 590411-10-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 100℃; for 25h;	A solution of 2-bromo-6-hydroxynaphthalene (1.15 g, TCI) in anhydrous THF (50 ml) was cooled to -78 C. under argon atmosphere, added dropwise with 1.6 M solution of n-butyllithium in hexane (6.88 ml, Ald) over 20 minutes and stirred for 30 minutes.The reaction mixture was added dropwise with triisopropyloxyborane (henceforth abbreviated as "(IPrO)3B, 1.73 ml, Ald) over 10 minutes, stirred for 30 minutes, then warmed to room temperature and further stirred for 2 hours.The reaction mixture was added with 0.5 M aqueous sulfuric acid (10 ml) and extracted with diethyl ether (100 ml*3).The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure to obtain crude <strong>[173194-95-1]6-hydroxy-2-naphthaleneboronic acid</strong> (1.85 g).A solution of this product in ethanol (5.0 ml), Intermediate 7 (1.16 g) and 2 M aqueous sodium carbonate (12.0 ml) were added with toluene (10.0 ml) and tetrakistriphenylphosphine palladium (0) (henceforth abbreviated as "(Ph3P)4Pd", 570 mg, Nacalai Tesque) and stirred at 100 C. for 25 hours.The reaction mixture was added with ethyl acetate (300 ml) and washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine.The organic layer was dried, and then the solvent was evaporated under reduced pressure.The residue was purified by flash column chromatography (hexane:ethyl acetate=6:1) to obtain the title compound (Compound No. 001, 1.04 g).

Reference： [1]Patent: US2004/44258,2004,A1 .Location in patent: Page 60

4
[ 848485-51-8 ]
[ 173194-95-1 ]
[ 898825-94-0 ]

Yield	Reaction Conditions	Operation in experiment
		Example 128Step 1. 3-Cyclohexyl-1-(2-morpholin-4-yI-2-oxo-ethyl)-2-(6-trifluoromethane- sulfonyloxy-naphthalen-2-y1)-1H-indole-6-carboxylic acid methyl ester (151)[0367] Compound 150 (200 mg, 0.38 mmol, prepared from compound 121 and 6- hydroxynaphthalen-2-y1boronic acid) and pyridine (460 muL, 0.57 mmol) were dissolved in 4 mL CH2Cl2 under argon and cooled to 0 C. Trifluoroacetic anhydride (479 mL, 2.8 mmol) was added. After 5 min, the reaction was allowed to warm to room temperature and washed with saturated sodium bicarbonate and water, and concentrated. The crude product was purified using RP-HPLC to give 134 mg (54 %) of compound 151. MS: 659.2 (M+H+); H1-NMR (DMSO-d6): delta(ppm) 8.25-8.19 (m, 3H), 8.02-8.00 (m, 2H), 7.88 (d, 1H, J=8.4Hz), 7.71-7.65 (m, 2H), 7.54 (d, 1H, J=8.4Hz), 4.99 (s, 2H), 3.86 (s, 3H), 3.44-3.31 (m, 8H), 2.63 (m, 1H), 1.87-1.61 (m, 7H), 1.30-1.15 (m, 3H).

Reference： [1]Patent: WO2006/76529,2006,A1 .Location in patent: Page/Page column 155

5
[ 5332-24-1 ]
[ 173194-95-1 ]
6-(quinolin-3-yl)-naphthalen-2-ol [ No CAS ]
[ 90449-28-8 ]

Yield	Reaction Conditions	Operation in experiment
74%; 9%	With potassium carbonate;palladium diacetate; In N,N-dimethyl-formamide; at 90℃; for 1.5 - 12h;	To a degassed solution of the aryl bromide (68, 74 or 77, Schemes 8 and 9) in DMF (4.0 niL) was added aryl boronic acid (53, 55, 63 or 71, 1.2 equiv), EPO <DP n="103"/>Pd(OAc>2 (0.05 equiv) and K2CO3 (2 equiv) at room temperature. After degassing and purging with argon (repeated thrice), the reaction mixture was stirred at 9O0C. Reaction times vary from 1.5 hours to 12 hours. The mixture was allowed to cool to room temperature and diluted with H2O (15 mL). The aqueous solution was extracted with ethyl acetate (5 x 15 mL) and the combined organic layer was concentrated under reduced pressure. The residue was purified by flash column chromatography.6-(Quinolin-3-yl)-naphthalen-2-ol (69)[00370] Light yellow solid (0.107 g, 74%). 1H NMR (DMSO): 7.18 (d, IH,J=8.7 ), 7.21 (s, IH), 7.67 (t, IH, J=7.3), 7.78 (t, IH, J=7.5), 7.86-7.95 (m, 3H), 8.07 (s, IH), 8.36 (s, IH), 8.74 (s, IH), 9.39 (s, IH), 9.90 (s, IH); 13C NMR (DMSO): 109.1, 119.8, 125.7, 126.4, 127.5, 127.6, 128.3, 128.5, 128.8, 129.2, 129.8, 130.5, 131.6, 132.8, 133.4, 134.7, 147.1, 150.2, 156.5.

Reference： [1]Patent: WO2006/125324,2006,A1 .Location in patent: Page/Page column 101-102

6
[ 36748-89-7 ]
[ 173194-95-1 ]
6-benzofuran-2-yl-naphthalen-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	With potassium carbonate;palladium diacetate; In N,N-dimethyl-formamide; at 90℃; for 2 - 2.5h;	To a degassed solution of 59, 60 or 62 (0.300-0.400 mmol) in DMF (4 mL) was added Pd(OAc)2 (0.05 eq.), K2CO3 (2 eq.) and 6-hydroxy-3- EPO <DP n="101"/>naphthaleneboronic acid 63 (1.3 eq.) at room temperature (Scheme 12). After degassing and purging with argon (repeated thrice), the reaction mixture was stirred at 9O0C for 2-2.5 hours. The mixture was allowed to cool to room temperature and diluted with H2O (15 mL). The aqueous solution was extracted with ethyl acetate (5 x 15 mL) and combined organic layer was concentrated under reduced pressure. The residue was purified by flash column chromatography using 30 % ethyl acetate in hexane as solvent system to afford 64, 65 or 66.6-Benzofiiotaran-2-yl-naphthalen-2-ol {betaA)[00365] Light brown solid (0.049 g, 46%); 1H NMR (CDCl3): 7.09 (s, IH),7.13-7.17 (m, 2H), 7.21-7.25 (m, 3H), 7.55 (d, IH, J=7.2), 7.59 (d, IH, J=6.7) 7.74 (d, IH, J=7.7), 7.84 (d, IH, J=7.6), 7.88 (d, IH, J=8.1), 8.31 (s, IH).

Reference： [1]Patent: WO2006/125324,2006,A1 .Location in patent: Page/Page column 99-100

7
[ 34128-30-8 ]
[ 173194-95-1 ]
3-(6-hydroxy-naphthalen-2-yl)-benzothiophene-2-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Patent: WO2006/125324,2006,A1 .Location in patent: Page/Page column 103-104

8
[ 265652-38-8 ]
[ 173194-95-1 ]
C₁₇H₁₄O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; lithium chloride;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; ethanol; water;Heating / reflux;	A solution of 4-bromo-3-methylthiophene carboxylic acid (1 g) in methanol was treated with a stock solution of trimethylsilyl diazomethane (2M hexanes) in excess. Upon full consumption of the carboxylic acid, the reaction mixture was quenched with acetic acid and concentrated in vacuo. This bromo methyl ester intermediate (100 mg, 0.43 mmol) was diluted into (0.1M, 1:1) ethanol-dioxane co- solvent, and combined with IM aqueous sodium bicarbonate (0.85 mL, 0.85 mmol), lithium chloride (36 mg, 0.85 mmol), 6-hydroxy-2-naphthyl boronic acid (160 mg, 0.85 mmol), and catalytic Pd(Ph3P)4. The reaction mixture was heated at reflux overnight, cooled, concentrated in vacuo, partitioned between water and methylene chloride, the organic phase concentrated, and the residue purified by preparative RPHPLC. The methyl ester was saponified at room temperature using excess IM aqueous lithium hydroxide in (3 : 1 : 1 ) THF-methanol-water. The reaction mixture was concentrated in vacuo to remove volatiles, acidified with IN aqueous HCl, and partitioned with water and 30% isopropanol-chloroform. The organic phase was concentrated in vacuo, and the dried solid (79 mg, 0.28 mmol) was diluted into methylene chloride (0.1 M), treated with triethylamine (0.12 mL, 0.83 mmol), methanesulfonyl chloride (0.027 mL, 0.34 mmol), and anthranilic acid (38 mg, 0.28 mmol). The reaction mixture was maintained at room temperature overnight, concentrated in vacuo, the solid acid (as naphthol sulfonate) treated with excess 1 M aqueous lithium hydroxide in (3 : 1 : 1 ) THF-methanol-water, again concentrated in vacuo to remove volatiles, acidified with IN aqueous HCl to pH7, and purified by preparative RPHPLC. 1H NMR (DMSO-d6, 500 MHz) delta 9.8 (s, IH), 8.6 (d, IH), 8.1 (d, IH), 7.8 (m, 4H), 7.6 (t, IH), 7.4 (d, IH), 7.2 (m, 3H), 2.5 (s, 3H); LCMS m/z 404 (M+l).

Reference： [1]Patent: WO2007/35478,2007,A2 .Location in patent: Page/Page column 24-25

9
[ 757905-89-8 ]
[ 173194-95-1 ]
2-(3-((1H-1,2,4-triazol-1-yl)methyl)-5-(2-hydroxynaphthalen-6-yl)phenyl)-2-methylpropanenitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With tetrabutylammomium bromide; potassium carbonate;palladium diacetate; In ethanol; water; at 150℃; for 0.166667h;Irradiation;	2-(3-((lH-l,254-Triazol-l-yl)methyI)-5-(2-hydroxynaphthalen-6-yI)phenyI)-2- methylpropanenitrile (TJA02061)C23H20N4O MW 368.43. A 10 mL microwave vial was loaded with TJA02004 (0.150 g, 0.492 mmol), TJA02057 (0.138 g, 0.737 mmol), potassium carbonate (0.170 g, 1.23 mmol), tetrabutylammonium bromide (0.164 g, 0.492 mmol), Pd(OAc)2 (0.003-0.004 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 Explorer Microwave. After a run time of 10 min at 150 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 via flash chromatography (20 g column, method4) which eluted the title compound as a light yellow solid (0.130 g, 72 %), mp 193.7-198.40C; R/. 0.42 (ethyl acetate);1B NMR (270 MHz, DMSO-d6) delta 1.76 (6H, s, ArC(CH3)2CN)5 5.55 (2H5 s, ArCH2N), 7.11-7.21 (2H, m5 ArH), 7.47 (IH, s, ArH), 7.66 (IH, s, ArH), 7.68-7.72 (IH, dd, J= 1.8 & 8.7 Hz, ArH), 7.79-7.81 (2H, m, ArH), 7.85-7.88 (IH, d, J= 8.7 Hz, ArH), 8.02 (IH, s, C2H2N3), 8.09 (IH, s, ArH), 8.76 (IH, s, C2H2N3) and 9.88 (IH, s, ArOH); 13C NMR (67.9 MHz, DMSO-d6) delta 28.9 (CH3), 37.4 (C), 52.6 (CH2), 109.0 (CH), 119.8 (CH), 123.6 (CH)5 124.1 (CH), 125.1 (C), 125.8 (CH), 126.1 (CH), 126.4 (CH), 127.4 (CH), 128.4 (C), 130.5 (CH)5 134.0 (C), 134.7 (C), 138.2 (C), 142.0 (C)5 143.3 (C), 145.0 (CH), 152.4 (CH) and 156.3 (C); HPLC (90 % CH3CN UiH2O) tr= 3.697 (100 %); LCMS (APCI), m/z 369.65 (M+ + H, 100 %).

Reference： [1]Patent: WO2007/68905,2007,A1 .Location in patent: Page/Page column 73-74

10
[ 173194-95-1 ]
[ 942154-19-0 ]
6-(3-(1H-1,2,4-triazol-1-ylmethyl)phenyl)naphthalen-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With tetrabutylammomium bromide; potassium carbonate;palladium diacetate; In ethanol; water; at 150℃; for 0.166667h;Irradiation;	6-(3-((lH-l,2,4-TriazoI-l-yl)methyI)phenyl)naphthaIen-2-ol (TJA02059) C19H15N3O MW 301.34. A 10 niL microwave vial was loaded with TJA01009 (0.150 g, 0.630 mmol), TJA02057 (0.178 g5 0.945 mmol), potassium carbonate (0.218 g, 1.58 mmol), tetrabutylammonium bromide (0.209 g5 0.630 mmol), Pd(OAc)2 (0.004-0.005 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 Explorer Microwave. After a run time of 10 min at 150 0C the reaction mixture was allowed to cool and ethyl acetate (50 mL) added. This was then washed with distilled water (25 mL x 3) and brine (25 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 via flash chromatography (20 g column, method4) which eluted the title compound as a white solid (0.155 g, 82 %), Rf. 0.51 (ethyl acetate); 1H NMR (270 MEIz, DMSO-J6) delta 5.50 (2H5 s, ArCH2N), 7.10-7.14 (2H, m, ArH), 7.23- 7.26 (IH5 d, J= 7.7 Hz, AxH)5 7.44-7.50 (IH5 1, J= 7.7 Hz5 ArH)5 7.66-7.86 (5H5 m, ArH), 8.00 (IH, S5 C2H2N3), 8.05 (IH5 s, ArH), 8.72 (IH5 S5 C2H2N3) and 9.85 (IH, bs5 ArOH); 13C NMR (67.9 MHz5 DMSO-J6) delta 52.7 (CH2), 109.0 (CH)5 119.7 (CH)5 125.7 (CH)5 125.8 (CH)5 126.8 (CH)5 126.9 (CH), 127.1 (CH)5 127.3 (CH)5 128.5 (C), 129.9 (CH), 130.4 (CH)5 134.4 (C)5 134.5 (C)5 137.5 (C)5 141.2 (C)5 144.9 (CH)5 152.3 (CH) and 156.2 (C);HPLC (90 % CH3CN in H2O) ttau= 3.136 (97.81 %); LCMS (APCI), m/z 300.38 (M - H, 100 %).

Reference： [1]Patent: WO2007/68905,2007,A1 .Location in patent: Page/Page column 143-144

11
[ 173194-95-1 ]
[ 189265-99-4 ]
[ 1027786-50-0 ]

Yield	Reaction Conditions	Operation in experiment
40%	With potassium carbonate;palladium diacetate; In N,N-dimethyl-formamide; at 20 - 90℃; for 1.5 - 12h;	Example 1 Preparation by Suzuki-coupling reaction[00149] Compounds QR-0159, QR-0160. and QR-0162 were prepared bySuzuki-coupling reaction. The synthesis reaction is depicted in Scheme 1 below (Tsis para-toluene sulfonic acid). <n="48"/>Scheme 1[00150] The following general procedure was used.General Procedure for Suzuki-coupling reaction[00151] To a degassed solution of the aryl halide (84, 86, 87 or 90, Schemes 1and 2) in DMF (4.0 - 6.0 mL) was added aryl boronic acid (53. 55. 63 or 85. 1.2 equiv.), Pd(OAc)2 (0.05 equiv.) and K2CO3 (2 equiv.) at room temperature. After degassing and purging with argon (done thrice), the reaction mixture was stirred at 9O0C. Reaction times varied from 1.5 hours to 12 hours. The mixture was allowed to cool to room temperature and diluted with H2O ( 15 mL). The aqueous solution wasextracted with ethyl acetate (5 x 15 mL) and the combined organic layer wasconcentrated under reduced pressure.

Reference： [1]Patent: WO2008/58402,2008,A1 .Location in patent: Page/Page column 46-48

12
[ 173194-95-1 ]
[ 1132940-53-4 ]
[ 1355646-93-3 ]

Yield	Reaction Conditions	Operation in experiment
88%	With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); 1,3,5,7-tetramethyl-8-phenyl-2,4,6-trioxa-8-phosphatricyclo[3.3.1.13,7]decane; In tetrahydrofuran; water; at 65℃; for 2.5h;Inert atmosphere;	Example 2Preparation of 1-(3-tert-butyl-5-(6-hydroxynaphthalen-2-yl)-4-methoxyphenyl)pyrimidine-2,4(1H,3H)-dione (compound (4)) This reaction is sensitive to oxygen, and so all vessels were sealed with rubber septa. All solution transfers were accomplished by cannula technique using nitrogen as the inert gas. Anhydrous tetrahydrofuran was sparged with nitrogen gas for 2 hours prior to use to render it anaerobic. Hereafter this is referred to as degassed tetrahydrofuran.A 100-mL round-bottom flask was charged with 12.9 g of potassium phosphate tribasic (60.8 mmol, 2.0 equivalents), a magnetic stir bar, and 60 mL of water. The mixture was stirred to dissolve the solids, and the aqueous solution was sparged with nitrogen gas for 2 hours prior to use. Hereafter this is referred to as the phosphate solution.A 100-mL round-bottom flask was purged with nitrogen gas and charged with 282 mg of tris(dibenzylideneacetone)dipalladium(0) (0.31 mmol, 0.02 equivalents Pd), 413 mg of phosphine ligand, 1,3,5,7-tetramethyl-8-phenyl-2,4,6-trioxa-8-phosphatricyclo[3.3.1.13,7]decane (1.4 mmol, 2.3 equivalents relative to Pd) and a magnetic stir bar. The flask was sealed with a septum and the atmosphere above the solids was purged with nitrogen gas. Sixty mL of degassed tetrahydrofuran was added to the flask and the mixture was stirred under a nitrogen atmosphere. This solution was sparged for 15 minutes prior to use and is hereafter referred to as the catalyst solution.A 500-mL jacketed reactor was equipped with an overhead stirrer and reflux condenser and the atmosphere was purged with nitrogen gas. The reactor was charged with 12.1 g of 1-(3-tert-butyl-5-iodo-4-methoxyphenyl)pyrimidine-2,4(1H,3H)-dione, (30.3 mmol, 1.0 equivalent) and 5.98 g of <strong>[173194-95-1]6-hydroxynaphthalen-2-ylboronic acid</strong> (31.8 mmol, 1.05 equivalents). The atmosphere was purged with nitrogen gas with stirring of the solid reagents for 20 minutes. The reactor was charged with 120 mL of degassed tetrahydrofuran, and the mixture was stirred to dissolve the solids. The solution was sparged with nitrogen gas for 10 minutes. The phosphate solution was added to the reactor by cannula, followed by the catalyst solution. The resulting biphasic mixture was stirred aggressively to ensure adequate phase mixing, and the jacket was warmed to 65 C. The reaction jacket was cooled to room temperature prior to quench.After 2.5 hours, the reaction jacket was cooled to room temperature prior to quench.The workup of the reaction was also conducted under anaerobic conditions. Fifty-seven grams of sodium chloride and 4.2 g of cysteine (15 weight equivalents relative to palladium catalyst) were dissolved in 300 mL of water, and the resulting solution was sparged for 2 hours prior to use. To quench the reaction, approximately of this solution was transferred to the reaction mixture by cannula under nitrogen gas and the resulting biphasic mixture was stirred vigorously for 2 hours. The mechanical agitation was halted, the two solutions were allowed to separate, and the aqueous solution was drained out of the reactor through the bottom valve. Approximately of the quench solution was transferred to the reaction mixture by cannula under nitrogen gas and the resulting biphasic mixture was stirred vigorously for 45 minutes. The mechanical agitation was halted, the two solutions were allowed to separate, and the aqueous solution was drained out of the reactor through the bottom valve. The final portion of the quench solution was transferred to the reaction mixture by cannula, the resulting biphasic mixture was stirred vigorously for 45 minutes and the aqueous solution was drained out of the reactor through the bottom valve.The remainder of the workup was not conducted under anaerobic conditions. The pale yellow organic solution was drained from the reactor through the bottom valve and filtered over a pad of grade 4 Filtrol (1 cm deep by 4.5 cm diameter). The reactor and filter cake were rinsed with 70 mL of tetrahydrofuran. The bulk of the solvent was distilled in vacuo (ca 90-130 torr) at ca 40 C. with good agitation from an overhead stirrer. The solution was concentrated to approximately 50 mL volume, during which time the product began to precipitate out. Ethyl acetate (100 mL, 8 volume/weight relative to product) was added to the mixture, and the resultant slurry was stirred overnight at room temperature. The crystalline material was isolated by filtration and the filter cake was washed twice with 20 mL portions of ethyl acetate. The wet-cake was air-dried on the filter and dried in a vacuum oven at 50 C. at approximately 250 torr with a gentle nitrogen sweep overnight.The desired product was isolated as a white solid (11.6 g, 96.4% potency vs. standard, 88% potency-adjusted yield). 1H NMR (400 MHz, DMSO-d6) delta ppm delta 11.39 (d, J=2.1 Hz, 1H), 9.82 (s, 1H), 7.91 (d, J=0.8 Hz, 1H), 7.80 (d, J=8.9 Hz, 1H), 7.77-7.74 (m, 2H), 7.58 (dd, J=8.5, 1.7 Hz, 1H), 7.32 (d, J=2.7 Hz, 1H), 7.27 (d, J=2....

Reference： [1]Patent: US2012/14913,2012,A1 .Location in patent: Page/Page column 26-27
[2]Journal of Organic Chemistry,2019,vol. 84,p. 4873 - 4892

13
[ 173194-95-1 ]
[ 1132935-63-7 ]

Reference： [1]Patent: US2012/14913,2012,A1
[2]Journal of Organic Chemistry,2019,vol. 84,p. 4873 - 4892

14
[ 173194-95-1 ]
[ 1355646-97-7 ]

Reference： [1]Patent: US2012/14913,2012,A1
[2]Journal of Organic Chemistry,2019,vol. 84,p. 4873 - 4892

15
[ 173194-95-1 ]
N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide sodium salt [ No CAS ]

Reference： [1]Patent: US2012/14913,2012,A1

16
[ 173194-95-1 ]
[ 1332333-20-6 ]
[ 1332332-38-3 ]

Yield	Reaction Conditions	Operation in experiment
23%	With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 150℃; for 0.25h;Inert atmosphere; Sealed tube; Microwave irradiation;	Example 1315-[(3S)-l-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4-(6-hydroxy-2- naphthalenyl)phenyl]-2,4-dihydro-3H-l,2,4-triazol-3-one a) A solution of 4-(4-bromophenyl)-5-[(3S)-l-(cyclopropylcarbonyl)-3- pyrrolidinyl]methyl}-2,4-dihydro-3H-l,2,4-triazol-3-one (0.256 mmol) in dioxane (1.5 mL) was treated with <strong>[173194-95-1](6-hydroxy-2-naphthalenyl)boronic acid</strong> (0.281 mmol),dichloro[l,l '-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (10 mg), and 2M aq potassium carbonate (0.767 mmol). The reaction mixture was purged with nitrogen, sealed, and irradiated in a microwave (Biotage Initiator) at 150 C for 15 min. The reaction mixture was cooled to room temperature and was diluted with water (50 mL). The aqueous layer was acidified to pH ~4 using IN aq HC1 and was extracted with dichloromethane. The aqueous phase was then diluted with brine (50 mL) and extracted with tetrahydrofuran, which was subsequently combined with thedichloromethane organic phase. The resulting organic phase was treated with Si-Thiol (Silicycle, 20 mg), dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by reverse phase HPLC (20-50% acetonitrile w/ 0.1 %TFA/water w/ 0.1% TFA). The product fractions from the HPLC were combined, adjusted to pH ~5 with the addition of saturated aq sodium bicarbonate, further diluted with brine, and extracted with tetrahydrofuran. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting product was purified by reverse phase HPLC (10-40% acetonitrile/water + 0.1% NH4OH) to afford the title compound as an amorphous white solid (23%). MS(ES)+ m/e 455.0 [M+H]+.

Reference： [1]Patent: WO2011/103546,2011,A1 .Location in patent: Page/Page column 147-148

17
[ 173194-95-1 ]
[ 1393534-90-1 ]
[ 1393534-95-6 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 6672 - 6675

18
[ 173194-95-1 ]
[ 1393534-90-1 ]
[ 1393534-96-7 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 6672 - 6675

19
[ 173194-95-1 ]
[ 37465-31-9 ]
[ 1426661-56-4 ]

Reference： [1]Green Chemistry,2013,vol. 15,p. 656 - 662
[2]ChemCatChem,2014,vol. 6,p. 2712 - 2718

20
[ 173194-95-1 ]
[ 34658-66-7 ]
[ 1354633-27-4 ]

Reference： [1]Patent: EP2597094,2013,A1

21
[ 173194-95-1 ]
[ 34658-66-7 ]
[ 1354633-23-0 ]

Yield	Reaction Conditions	Operation in experiment
75%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; for 8h;Inert atmosphere; Reflux;	A mixture of 1.57 g (5.73 mmol) of 2-(4-bromophenyl)-imidazo[1,2-a]pyridine, 1.19 g (6.30 mmol) of <strong>[173194-95-1]6-hydroxynaphthalen-2-ylboronic acid</strong>, 0.20 g (0.172 mmol) of tetrakis(triphenylphosphine)palladium(O), 20 ml of 1,2-dimethoxyethane, and 10 ml of a 2 M sodium carbonate aqueous solution was heated and refluxed for 8 hours in an argon atmosphere. The reaction mixture was cooled to room temperature, and neutralized using dilute hydrochloric acid. The resulting solid was filtered off, washed with a methanol-water mixture, and dried. The resulting solid was washed with toluene to obtain 1.45 g of 6-{4-(imidazo[1,2-a]pyridin-2-yl)phenyl}-2-naphthol (yield: 75%).

Reference： [1]Patent: EP2597094,2013,A1 .Location in patent: Paragraph 0094

22
[ 173194-95-1 ]
[ 2873-29-2 ]
[ 1453856-03-5 ]

Yield	Reaction Conditions	Operation in experiment
49%	With palladium diacetate; In acetonitrile; at 20℃;	Prepared from (2R,3S,4R)-3,4-diacetoxy-3,4-dihydro-2H-pyran-2-yl]methyl acetate (1.49 g, 5.47 mmol) and <strong>[173194-95-1](6-hydroxy-2-naphthyl)boronic acid</strong> (l.Og, 5.32 mmol) following the same procedure than INTERMEDIATE A, step I. Purification by flash chromatography on Biotage snap 50g cartridge using a gradient of EtOAc in hexanes (0-50%) affords the title compound an off-white foamy solid (935 mg, 49% yield).
49%	With palladium diacetate; In acetonitrile; at 20℃;Inert atmosphere;	Step I: [(2R,3 S,6S)-3-Acetoxy-6-(6-hydroxy-2-naphthyl)-3,6-dihydro-2H-pyran-2-yl]methyl acetate Acetonitrile (10 mL) is added to a mixture of [(2R,3S,4R)-3,4-diacetoxy-3,4-dihydro- 2H-pyran-2-yl]methyl acetate (1.49 g, 5.47 mmol), <strong>[173194-95-1](6-hydroxy-2-naphthyl)boronic acid</strong> (1.0 g, 5.32 mmol) and diacetoxypalladium (119 mg, 0.53 mmol). The reaction mixture is stirred overnight at RT under N2, then filtered through silica cartridge (5 g), and rinsed with EtOAc. Combined filtrates are concentrated, and purified on Biotage SNAP 50 g silica gel cartridge using a gradient of EtOAc in Hex (0-50%). Pure fractions are combined and concentrated to provide title compound (935 mg, 2.62 mmol, 49% yield) as an off-white foamy solid. XH NMR (400 MHz, CDC13) delta 7.80 - 7.72 (m, 2H), 7.70 (d, J= 8.5 Hz, 1H), 7.51 (dd, J= 8.5, 1.7 Hz, 1H), 7.18 - 7.08 (m, 2H), 6.28 (ddd, J= 10.4, 3.1, 1.6 Hz, 1H), 6.13 - 6.00 (m, 1H), 5.49 - 5.42 (m, 1H), 5.36 (ddd, J= 7.4, 4.1, 2.1 Hz, 1H), 4.28 (dd, J= 12.0, 5.8 Hz, 1H), 4.09 (dd, J= 12.0, 3.0 Hz, 1H), 3.86 (ddd, J= 7.8, 5.8, 3.0 Hz, 1H), 2.10 (s, 3H), 2.08 (s, 3H). LC-MS:m/z = 357.34 (M+ H +).

Reference： [1]Patent: WO2013/134415,2013,A1 .Location in patent: Page/Page column 167
[2]Patent: WO2014/100158,2014,A1 .Location in patent: Page/Page column 150

23
[ 50-00-0 ]
[ 173194-95-1 ]
C₂₂H₁₈B₂O₆ [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2013,vol. 355,p. 2208 - 2216

24
[ 50-00-0 ]
[ 173194-95-1 ]
C₂₁H₁₆B₂O₆ [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2013,vol. 355,p. 2208 - 2216

25
[ 173194-95-1 ]
[ 1616111-99-9 ]