[ CAS No. 762287-57-0 ] {[proInfo.proName]}

Name: 762287-57-0|(4-Chloro-2-methoxyphenyl)boronic acid|98%
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Quality Control of [ 762287-57-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 762287-57-0 ]

Product Details of [ 762287-57-0 ]

CAS No. :	762287-57-0	MDL No. :	MFCD02684317
Formula :	C₇H₈BClO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NZRRMTBNTSBIFH-UHFFFAOYSA-N
M.W :	186.40	Pubchem ID :	3858606
Synonyms :	Boronic acid,(4-chloro-2-methoxyphenyl)-;4-Chloro-2-methoxybenzeneboronic Acid (contains varying amounts of Anhydride)

Calculated chemistry of [ 762287-57-0 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	47.77
TPSA :	49.69 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 :	No
Log Kp (skin permeation) :	-6.42 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.43
Log Po/w (WLOGP) :	0.03
Log Po/w (MLOGP) :	0.6
Log Po/w (SILICOS-IT) :	-0.1
Consensus Log Po/w :	0.39

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.13
Solubility :	1.37 mg/ml ; 0.00734 mol/l
Class :	Soluble
Log S (Ali) :	-2.08
Solubility :	1.56 mg/ml ; 0.00834 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.03
Solubility :	1.73 mg/ml ; 0.00927 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.95

Safety of [ 762287-57-0 ]

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 [ 762287-57-0 ]

* 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 [ 762287-57-0 ]
Downstream synthetic route of [ 762287-57-0 ]

[ 762287-57-0 ] Synthesis Path-Upstream 1~3

1
[ 174913-09-8 ]
[ 121-43-7 ]
[ 762287-57-0 ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 0.666667 h; Inert atmosphere Stage #2: at 20℃; for 3 h; Inert atmosphere	Synthesis of Intermediate I-1 10262] 22.1 g (100 mmol) of 2-bromo-5-chioroanisole was dissolved in 500 ml of THF, and stirred in a N2 atmosphere at—78° C. for 10 minutes. Then, 44 mL of 2.5 M n-BuLi was slowly added thereto by using a dropping funnel, and the mixture was additionally stirred for 30 minutes. 10.4 g (110 mmol) of trimethyl borate was slowly and dropwisely added thereto by using a dropping flannel, and the mixture was additionally stirred for 3 hours at room temperature. Next, an organic layer was extracted therefrom once by using 300 ml of 1 M HC1 and three times by using water and diethylether. The organic layer was dried using magnesium sulfate, and a solvent was removed thereform by evaporation. The residue was separated and purified through a silica gel chromatography to obtain 13.61 g of Intermediate 1-1 (73 mmol, yield:73percent). The compound thus obtained was confirmed by usingMS/FAB.10263] C7H8BC103 Cal. 186.40. Found. 186.47.
50%	Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1 h; Stage #2: at 20℃; for 24 h;	10272] 5.2 g (23.6 mmol) of 2-bromo-5-chloroanisole was dissolved in 100 mE of tetrahydroffiran (THF). 10 mE (25.0 mmol) of n-l3uEi (2.5M in hexane) was slowly added drop- wise thereto at —78° C. The result was stirred at the same temperature for 1 hour. Then, 9.3 mE (50.0 mmol) of trim- ethyl borate was slowly added dropwise thereto, and stirred for 24 hours at room temperature. Once the reaction was complete, 10percent aqueous HC1 solution was added thereto to adjust pH to about 5. Then, an organic layer was extracted three times therefrom by using diethylether. The obtained organic layer was dried by using magnesium sulfate (Mg504). Then, a solvent was removed therefrom by evaporation. The obtained residue was purified by recrystallization, thereby obtaining 3.15 g of Intermediate 1-1 (yield: 50percent).

Reference： [1] Organic Letters, 2016, vol. 18, # 15, p. 3630 - 3633
[2] Patent: US2016/190448, 2016, A1, . Location in patent: Paragraph 0261; 0262; 0263
[3] Patent: US2016/190449, 2016, A1, . Location in patent: Paragraph 0271; 0272

2
[ 174913-09-8 ]
[ 762287-57-0 ]

Reference： [1] Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6626 - 6637

3
[ 762287-57-0 ]
[ 1377503-12-2 ]

Reference： [1] Patent: WO2012/66442, 2012, A1,

[ 762287-57-0 ] Synthesis Path-Downstream 1~80

1
[ 762287-57-0 ]
[ 694-80-4 ]
[ 852118-14-0 ]

Yield	Reaction Conditions	Operation in experiment
73%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 82℃;	Intermediate 86 2,2'-Dichloro-6-methoxy-biphenyl: To a solution of 2-chlorobromobenzene (15.5 g, 80.6 mmol) and sodium carbonate (9.0 g, 84.9 mmol) in DME-water (5:1) was added 2-chloro-6-methoxybenzene boronic acid (5.0 g, 26.8 mmol) at 82 C., followed by tetrakis(triphenylphosphine)palladium (0) (1.5 g, 1.4 mmol). The reaction mixture was heated at 82 C. overnight and cooled to room temperature. The mixture was extracted with ethyl acetate and washed with water. The organic solvent was removed under vacuum. Chromatography with 5% ethyl acetate in hexanes afforded 5.0 g (73%) of the title compound as a colorless oil.

Reference： [1]Patent: US2006/241172,2006,A1 .Location in patent: Page/Page column 57

2
[ 877383-54-5 ]
[ 762287-57-0 ]
[ 877383-55-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; for 16h;Heating / reflux;	The product of step a) (0.6 g), 4-chloro-2-methoxy boronic acid (0.69 g), toluene (10ml), ethanol (4 ml) and 2M Na2CC>3 (2 ml) were charged to a flask and stirred.Tetrakistriphenylphospine palladium (0) (0.09 g) was added and the mixture stirred at refluxfor 16 h. The mixture was concentrated in vacuo. The residue was purified by flash columnchromatography eluting with isohexane:ethyl acetate (6:4) to give the sub-title compound.Yield 0.68g.MS: ESI (+ve): 350 (M+H)

Reference： [1]Patent: WO2006/21759,2006,A1 .Location in patent: Page/Page column 46

3
[ 1121-76-2 ]
[ 762287-57-0 ]
[ 1173157-19-1 ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 120℃; for 3h;	4-Chloropyridine-jV-oxide (500 mg, 3.85 mmol), 2-methoxy-4- chlorophenylboronic acid (862 mg, 4.63 mmol) and K2CO3 (1.59 g, 11.55 mmol) were suspended in DMSO (5 mL) and PdCl2(dppf) (314 mg, 0.385 mmol) was added. The reaction mixture was placed under vacuum for 20 min and flushed with N2. This process was repeated, and the reaction mixture was heated at 120 0C for 3 h. The reaction mixture was cooled to 25 0C and partitioned between methylene chloride and 5% lithium chloride. The aqueous phase was removed, and the organic phase was washed with brine, dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. Flash chromatography (ISCO 40 g column, methylene chloride/MeOH 100:0 to 90:10) provided the title compound (673 mg, 74%) as a tan solid: 1H NMR (300 MHz, CD3OD) delta 8.21 (dd, J= 5.4, 1.8 Hz, 2H), 7.47 (dd, J= 5.6, 1.6 Hz, 2H), 7.26 (d, J= 8.2 Hz, IH), 7.06 (dd, J = 8.3, 2.4 Hz, IH), 7.00 (d, J= 1.7 Hz, IH), 3.87 (s, 3H); ESI MS m/z 235 [M + H]+.

Reference： [1]Patent: WO2009/89482,2009,A1 .Location in patent: Page/Page column 189

4
[ 762287-57-0 ]
[ 959139-32-3 ]
[ 959132-85-5 ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃; for 5h;Inert atmosphere;	Example 2162-[3-(4-chloro-2-methoxyphenyl)-4-(2-fluorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-N-[1-methyl-1-(3-trifluoromethyl-phenyl)ethyl]-acetamide Under argon, 70 mg (0.14 mmol) of the bromide from Example 141A and 35.4 mg of (2-methoxy-4-chlorophenyl)boronic acid (0.19 mmol) are dissolved in 1.75 ml of degassed DMF and treated with 204 mul of a degassed 2 M sodium carbonate solution in water (0.41 mmol). Ca. 8 mg of tetrakis-(triphenylphosphine)palladium (ca. 7 mumol) are added and the mixture heated at 90 C. for 5 hrs. After cooling, it is filtered, the solid washed with a little DMSO and the total filtrate separated by preparative HPLC (Method 20). 65 mg (83% of theory) of the title compound are obtained.LC/MS [Method 7]: Rt=2.63 min; m/z=577 (M+H)+. 1H-NMR (400 MHz, DMSO-d6): delta=1.60 (s, 6H), 3.68 (s, 3H), 4.49 (s, 2H), 4.71 (s, 2H), 6.96-7.08 (m, 4H), 7.16 (d, 1H), 7.19-7.28 (m, 2H), 7.48-7.57 (m, 2H), 7.62 (s, 1H), 7.67 (d, 1H), 8.51 (br. s, 1H).

Reference： [1]Patent: US2009/312381,2009,A1 .Location in patent: Page/Page column 156

5
[ 762287-57-0 ]
[ 1238196-66-1 ]

Yield	Reaction Conditions	Operation in experiment
87%		To a solution of the commercially available <strong>[762287-57-0][4-chloro-2-(methyloxy)phenyl]boronic acid</strong> (1.0 g, 5.36 mmol) in DCM was added boron tribromide (1 M solution in DCM, 10.73 ml_, 10.73 mmol) and the reaction was stirred at RT for 1 hour. The reaction was quenched by addition of ice, and the organic phase was separated. The aqueous phase was extracted with DCM, dried over sodium sulfate and evaporated in vacuo. The title compound, (4-chloro-2-hydroxyphenyl)boronic acid was obtained as a white powder (800 mg, 4.64 mmol, 87% yield).LCMS: (M-H)+ = 171 ; Rt= 4.40 min.
	With boron tribromide; In dichloromethane; at 0 - 20℃; for 19h;	Preparation 17: (4-chloro-2-hvdroxyphenyl)boronic acidHTo a solution of <strong>[762287-57-0](4-chloro-2-methoxyphenyl)boronic acid</strong> (1.0 g, 5.36 mmol) in dichloromethane (5 mL) at 0C was added boron tribromide (1 M in dichloromethane, 10 mL, 10 mmol). The reaction was stirred at 0C for 1 hour, then allowed to warm to room temperature and stirred as such for 18 hours. The reaction was quenched carefully with water. The resulting precipitate was collected by filtration, to give a white solid, 260 mg. The layers were separated and the organic layer was dried over Na2S04 and concentrated in vacuo to give a white solid, 300 mg. The two batches of solid were combined to give the title compound as a white solid, 560 mg, in a 61 % yield. This material was taken on to Preparation 18 without purification.

Reference： [1]Patent: WO2011/138307,2011,A1 .Location in patent: Page/Page column 62; 63
[2]Journal of Combinatorial Chemistry,2010,vol. 12,p. 664 - 669
[3]Patent: WO2012/66442,2012,A1 .Location in patent: Page/Page column 30

6
[ 762287-57-0 ]
[ 1039826-64-6 ]
[ 1108184-76-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7020 - 7023

7
[ 762287-57-0 ]
[ 1039042-31-3 ]
[ 1039042-34-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7015 - 7019

8
[ 762287-57-0 ]
[ 1265397-22-5 ]
[ 1265399-69-6 ]

Yield	Reaction Conditions	Operation in experiment
60%	With N-ethyl-N,N-diisopropylamine;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 2.5h;Sealed tube;	A suspension of methyl 2-(4-chloro-6-methyl-2-phenylpyrimidin-5-yl)pentanoate (0.239 g; 0.75 mmol), tetrakis(triphenylphosphine) palladium(O) (0.087 mg; 0.075 mmol), N, N- diisopropylethylamine (0.517 ml 3 mmol) and <strong>[762287-57-0]4-chloro-2-methoxyphenylboronic acid</strong> (0.210 g; 1.125 mmol) ina mixture DME-water (2 ml_) was heated in a sealed tube for 2.5 h. The mixture was diluted with brine and extracted with ethyl acetate. The combined organics were dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (5 - 40 %) in heptane furnished 0.19O g (60 %) of the title compound as a colorless oil.ESI/APCI(+): 425 (M+H).

Reference： [1]Patent: WO2011/15641,2011,A1 .Location in patent: Page/Page column 130

9
[ 762287-57-0 ]
[ 1355070-71-1 ]
[ 1354960-49-8 ]

Yield	Reaction Conditions	Operation in experiment
36%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; for 6h;Inert atmosphere; Reflux;	4-(Bromomethyl)-2,5-difluoro-N-(methylsulfonyl)benzamide (Preparation 164, 100 mg, 0.27 mmol), <strong>[762287-57-0](4-chloro-2-methoxyphenyl)boronic acid</strong> (55 mg, 0.295 mmol), tetrakis(triphenylphosphine)palladium (31 mg, 0.027 mmol), aqueous potassium carbonate solution (1.8 M, 0.45 mL, 0.804 mmol) and tetrahydrofuran (15 mL) were combined and stirred under nitrogen at reflux for 6 hours. After cooling, the mixture was filtered through Celite and the filtrate evaporated. The residue was dissolved in water (20 mL) and acidified with aqueous potassium hydrogen sulphate solution (0.5 M) to pH 2 and the mixture extracted with ethyl acetate (1×30 mL). The organic layer was separated and back-washed with brine (2×20 mL). The organic layer was separated, dried over sodium sulphate, filtered and evaporated to give an orange oil. The oil was purified using silica gel column chromatography eluting with heptane to ethyl acetate:heptane 1:1 to give a solid. The solid was further purified by reverse phase HPLC to give the title compound (38 mg, 36%) as a white solid.LCMS Rt=2.32 minutes MS m/z 390 [MH]+

Reference： [1]Patent: US2012/10207,2012,A1 .Location in patent: Page/Page column 31

10
[ 762287-57-0 ]
[ 120068-79-3 ]
[ 1373210-81-1 ]

Yield	Reaction Conditions	Operation in experiment
60%	With bis-triphenylphosphine-palladium(II) chloride; N-iodo-succinimide; sodium hydrogencarbonate; In ethanol; water; at 80℃; for 18h;Inert atmosphere;	General procedure: Phenylpyrazole (0.2 mmol), arylboronic acid (0.4 mmol), NIS (0.2 mmol), [Pd] (10 mol%), NaHCO3 (0.4 mmol) and C2H5OH:H2O (3:1, 10 mL), were added to a Schlenk tube. Then the tube was charged with N2 and the reaction mixture was stirred at 80 C for 18 h. After the completion of the reaction, as monitored by TLC, the mixture was cooled and filtrated. The filtrate was extracted with ethyl acetate and washed with brine. Then the combined organic extracts were dried over Na2SO4, concentrated under vacuum and the resulting residue was purified by silica gel column chromatography to afford the desired products.

Reference： [1]Journal of Fluorine Chemistry,2012,vol. 137,p. 44 - 49

11
[ 762287-57-0 ]
methyl (2S)-tert-butoxy[4-(4-chloro-2-hydroxyphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid [ No CAS ]

Reference： [1]Patent: WO2012/66442,2012,A1

12
[ 762287-57-0 ]
[ 1377503-12-2 ]

Reference： [1]Patent: WO2012/66442,2012,A1

13
[ 762287-57-0 ]
[ 1312098-71-7 ]
[ 1353572-40-3 ]

Yield	Reaction Conditions	Operation in experiment
79%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 100℃;	A mixture of 4-bromo-3-(4- hydroxyphenyl)thiophene-2-carbaldehyde (Scheme II, 8, Xi = 4-hydroxyphenyl) (300 mg, 1.1 mmol), <strong>[762287-57-0]4-chloro-2-methoxyphenylboronic acid</strong> (Scheme II, 9A, X2 = 4-chloro-2- methoxyphenyl) (237 mg, 1.3 mmol), Na2C03 (225 mg, 2.2 mmol), and Pd(PPh3)4 (61 mg, 0.05 mmol) in toluene/EtOH/H20 (10 mL, 5:3:2) was heated at 100C, and stirred overnight under nitrogen. When TLC indicated that the starting material was consumed, the mixture was diluted with water, neutralized to pH=4-5 with HC1 (1M), extracted with EtOAc, concentrated, and purified by column chromatography (PE:EtOAc=20: l) to give 4-bromo-3-(4- hydroxyphenyl)thiophene-2-carbaldehyde (Scheme II, 9, Xi = 4-hydroxyphenyl, X2 = 4-chloro- 2-methoxyphenyl) (290 mg, yield 79%) as a white solid. 1H NMR (DMSO-J6400 MHz): delta 9.54 (s, 1H), 9.50 (s, 1H), 7.90 (s, 1H), 6.98 (d, J = 8.0 Hz, 1H), 6.89 (m, 4H), 6.58 (d, J = 8.4 Hz, 2H), 3.29 (s, 3H).

Reference： [1]Patent: WO2011/75478,2011,A1 .Location in patent: Page/Page column 42

14
[ 762287-57-0 ]
[ 1454667-90-3 ]
[ 168267-41-2 ]
[ 1454666-86-4 ]

Yield	Reaction Conditions	Operation in experiment
35%		Step 2 : 5 -(3 ',4'-difluoro-3 -methoxy- [1, 1 '-biphenyl] -4-yl)-N-( 1 ,3 ,4-thiadiazol-2-yl)-3 ,4- dihydroisoquinoline-2( 1 H)-sulfonamide A microwave vial charged with Pd(Amphos)2Ci2 (9.43 mg, 0.013 mmol), (4-chloro-2- methoxy)phenylboronic acid (0.050 g, 0.266 mmol), 5-bromo-N-(l,3,4-thiadiazol-2-yl)-3,4- dihydroisoquinoline-2(lH)-sulfonamide (0.100 g, 0.266 mmol), potassium phosphate (0.339 g, 1.599 mmol), 1.5 mL of dioxane and 0.25 mL of water was heated to 150C in the microwave for 30 minutes. (3,4-difluorophenyl)boronic acid (0.053 g, 0.333 mmol) and an additional portion of Pd(Amphos)2Ci2 (9.43 mg, 0.013 mmol) were added, and the reaction mixture was heated to 150C in the microwave for an additional 30 minutes. The aqueous layer was removed, and the reaction mixture was treated with HC1 (4N in dioxane) (0.266 ml, 1.066 mmol). After stirring for 10 minutes, the reaction mixture was concentrated. Purification of the crude residue by reverse phase column chromatography [RediSep Gold C18, 10-100% (0.1%NH4OH in MeOH)/(0.1%NH4OH in water)] gave 5-(3',4'-difluoro-3- methoxy- [1, 1 '-biphenyl] -4-yl)-N-( 1 ,3 ,4-thiadiazol-2-yl)-3 ,4-dihydroisoquinoline-2( 1 H)- sulfonamide (0.048 g, 0.093 mmol, 35.0 % yield). 'H NMR (MeCN-d3) delta: 8.31 (s, 1H), 7.65 (ddd, J = 12.2, 7.8, 2.2 Hz, 1H), 7.52 (dddt, J = 7.1, 4.3, 2.7, 1.2 Hz, 1H), 7.37 (dt, J = 10.6, 8.5 Hz, 1H), 7.14 - 7.27 (m, 4H), 7.07 - 7.12 (m, 1H), 6.99 - 7.05 (m, 1H), 4.20 - 4.41 (m, 2H), 3.81 (s, 3H), 3.30 - 3.39 (m, 1H), 3.12 - 3.24 (m, 1H), 2.63 - 2.76 (m, 1H), 2.42 - 2.55 (m, 1H); (M+H)+= 515.0.

Reference： [1]Patent: WO2013/134518,2013,A1 .Location in patent: Page/Page column 99; 100

15
[ 174913-09-8 ]
[ 762287-57-0 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 6626 - 6637

16
[ 762287-57-0 ]
[ 1236073-91-8 ]
[ 1448857-84-8 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 6626 - 6637

17
[ 762287-57-0 ]
1-(2-[{(1H-pyrazol-3-yl)}oxymethyl]-3-methylphenyl)-4-methyl-1,4-dihydrotetrazole-5-one [ No CAS ]
1-(2-[1-(4-chloro-2-methoxyphenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methylphenyl)-4-methyl-1,4-dihydroteterazole-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.15 g	With pyridine; copper diacetate; In acetonitrile; for 15h;Molecular sieve; Reflux;	A mixture of 1-(2-[1H-pyrazol-3-yl]oxymethyl}-3-methylphenyl)-4-methyl-1,4-dihydroteterazole-5-one (described in Reference Preparation Example 14) 1.00 g, <strong>[762287-57-0]4-chloro-2-methoxyphenyl boronic acid</strong> 0.78 g, copper(II) acetate 0.98 g, pyridine 0.59 mL, molecular sieve 4A 1.50 g, and acetonitrile 15 mL was stirred with heating under reflux for fifteen hours. To the reaction mixtures after standing to cool was added water, and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chloro-2-methoxyphenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methylphenyl)-4-methyl-1,4-dihydroteterazole-5-one (hereinafter referred to as Present tetrazolinone compound 11) 0.15 g. Present tetrazolinone Compound 11 1H-NMR (CDCl3) delta: 7.87 (1H, d, J 32 2.5 Hz), 7.65 (1H, d, J=8.5 Hz), 7.42-7.37 (2H, m), 7.26-7.24 (1H, m), 7.03 (1H, dd, J 32 8.5, 2.3 Hz), 6.99 (1H, d, J=2.3 Hz), 5.77 (1H, d, J=2.5 Hz), 5.30 (2H, s), 3.89 (3H, s), 3.63 (3H, s), 2.55 (3H, s).
0.15 g	With copper diacetate; In acetonitrile; for 15h;Reflux; Molecular sieve;	Preparation Example 11 A mixture of 1-(2-[1H-pyrazol-3-yl]oxymethyl}-3-methylphenyl)-4-methyl-1,4-dihydroteterazole-5-one (described in Reference Preparation Example 14) 1.00 g, <strong>[762287-57-0]4-chloro-2-methoxyphenyl boronic acid</strong> 0.78 g, copper(II) acetate 0.98 g, pyridine 0.59 mL, molecular sieve 4A 1.50 g, and acetonitrile 15 mL was stirred with heating under reflux for fifteen hours. To the reaction mixtures after standing to cool was added water, and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chloro-2-methoxyphenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methylphenyl)-4-methyl-1,4-dihydroteterazole-5-one (hereinafter referred to as Present tetrazolinone compound 11) 0.15 g. Present Tetrazolinone Compound 11 1H-NMR (CDCl3) delta: 7.87 (1H, d, J=2.5 Hz), 7.65 (1H, d, J=8.5 Hz), 7.42-7.37 (2H, m), 7.26-7.24 (1H, m), 7.03 (1H, dd, J=8.5, 2.3 Hz), 6.99 (1H, d, J=2.3 Hz), 5.77 (1H, d, J=2.5 Hz), 5.30 (2H, s), 3.89 (3H, s), 3.63 (3H, s), 2.55 (3H, s).
0.15 g	With pyridine; copper diacetate; In acetonitrile; for 15h;Molecular sieve; Reflux;	A mixture of 1-(2-[1H-pyrazol-3-yl]oxymethyl}-3-methylphenyl)-4-methyl-1,4-dihydroteterazole-5-one (described in Reference Preparation Example 14) 1.00 g, <strong>[762287-57-0]4-chloro-2-methoxyphenyl boronic acid</strong> 0.78 g, copper(II) acetate 0.98 g, pyridine 0.59 mL, molecular sieve 4A 1.50 g, and acetonitrile 15 mL was stirred with heating under reflux for fifteen hours. To the reaction mixtures after standing to cool was added water, and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chloro-2-methoxyphenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methylphenyl)-4-methyl-1,4-dihydroteterazole-5-one (hereinafter referred to as Present tetrazolinone compound 11) 0.15 g.

0.15 g	With pyridine; copper diacetate; In acetonitrile; for 15h;Molecular sieve; Reflux;	(2 - [1H- pyrazol-3-yl] oxy} methyl-3-methylphenyl) Reference Preparation Example 14, 1-described 4-methyl-1,4-dihydro-tetrazol-5-one 1.00 g, 4-chloro-2-methoxy-phenylboronic acid 0.78 g, copper acetate (II) 0.98 g, pyridine 0.59 mL, 1.50 g 4A molecular sieves and 15 mL of acetonitrile and the mixture was heated under reflux for 15 hours with stirring.By adding water to the reaction mixture bangraeng, followed by extracting with ethyl acetate.To the organic layer was washed with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure.By applying the resulting residue to silica gel column chromatography to give 1- (2 - [1- (4-chloro-2-methoxyphenyl) -1H- pyrazol-3-yl] oxy} methyl-3-methylphenyl ) -4-methyl-1,4-dihydro-tetrazol-5-one (hereinafter referred to as the present compound 11, tetra BBIT) to give 0.15 g.
0.15 g	With pyridine; copper diacetate; In acetonitrile; for 15h;Molecular sieve;	A mixture of 1-(2-[1H-pyrazol-3-yl]oxymethyl}-3-methylphenyl)-4-methyl-1,4-dihydroteterazole-5-one (described in Reference Preparation Example 14) 1.00 g, <strong>[762287-57-0]4-chloro-2-methoxyphenyl boronic acid</strong> 0.78 g, copper(II) acetate 0.98 g, pyridine 0.59 mL, molecular sieve 4A 1.50 g, and acetonitrile 15 mL was stirred with heating under reflux for fifteen hours. To the reaction mixtures after standing to cool was added water, and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chloro-2-methoxyphenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methylphenyl)-4-methyl-1,4-dihydroteterazole-5-one (hereinafter referred to as Present tetrazolinone compound 11) 0.15 g.
0.15 g	With copper diacetate; In acetonitrile; for 15h;Reflux;	A mixture of 1-(2-[H-pyrazol-3-yl]oxymethyl}-3-methylphenyl)-4-methyl-1,4-dihydroteterazole-5-one (described in Reference Preparation Example 14) 1.00 g, <strong>[762287-57-0]4-chloro-2-methoxyphenyl boronic acid</strong> 0.78 g, copper(II) acetate 0.98 g, pyridine 0.59 mL, molecular sieve 4A 1.50 g, and acetonitrile 15 mL was stirred with heating under reflux for fifteen hours. To the reaction mixtures after standing to cool was added water, and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[l-(4-chloro-2-methoxyphenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methylphenyl)-4-methyl-1,4-dihydroteterazole-5-one (hereinafter referred to as Present tetrazolinone compound 11) 0.15 g. (0223) Present Tetrazolinone Compound 11 (0224) 1H-NMR (CDCl3) delta: 7.87 (1H, d, J=2.5 Hz), 7.65 (1H, d, J=8.5 Hz), 7.42-7.37 (2H, m), 7.26-7.24 (1H, m), 7.03 (1H, dd, J=8.5, 2.3 Hz), 6.99 (1H, d, J=2.3 Hz), 5.77 (1H, d, J=2.5 Hz), 5.30 (2H, s), 3.89 (3H, s), 3.63 (3H, s), 2.55 (3H, s).

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 887
[2]Patent: US2016/165890,2016,A1 .Location in patent: Paragraph 0250; 0251; 0252
[3]Patent: US2016/157488,2016,A1 .Location in patent: Paragraph 0222; 0223; 0224
[4]Patent: KR2016/33208,2016,A .Location in patent: Paragraph 0281 - 0285
[5]Patent: KR2016/33206,2016,A .Location in patent: Paragraph 0356-0364
[6]Patent: KR2016/33207,2016,A .Location in patent: Paragraph 0286-0290
[7]Patent: US2016/150788,2016,A1 .Location in patent: Paragraph 0222-0224

18
[ 762287-57-0 ]
2-[1-(4,5-dihydro-4-methyl-5-oxo-1H-tetrazole-1-yl)-3-methylphenyl-2-yl]methyloxy}-4-bromothiazole [ No CAS ]
2-[1-(4,5-dihydro-4-methyl-5-oxo-1H-tetrazole-1-yl)-3-methylphenyl-2-yl]methyloxy}-4-(4-chloro-2-methoxyphenyl)thiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.30 g	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; cesium fluoride; In 1,4-dioxane; at 90℃; for 3h;	Preparation example 143A mixture of Present compound (T057) 0.30 g, <strong>[762287-57-0]4-chloro-2-methoxyphenylboronic acid</strong> 0.29 g, cesium fluoride 0.42 g,[1,1? -bis(diphenylphosphino) ferrocene}palladium(II) dichloride dichloromethane adduct 0.06 g and dioxane 6 mL was stirred at 90C for three hours. After cooling the reaction mixtures, the mixtures were filtered and thefiltrates were concentrated under reduced pressure. The resulting residues were subjected to a silica gel column chromatography to give 2-{ [1- (4,5-dihydro-4-methyl-5-oxo-- 1H-tetrazole-1-yl)-3--methylphenyl-2--yl]methyloxy}-4- (4- chloro-2-methoxyphenyl) thiazole (hereinafter, referred toas ??Present compound (T143) ??) 0.30 g.?H NMR (CDC13) oe: 2.56(3H, 5), 3.60(3H, 5), 3.93(3H, s), 5.57(2H, s), 6.94(1H, d, J=2.0Hz) , 7.03(1H, dd, J=8.4, 2.0Hz), 7.27(1H, dd, J=6.8, 2.4Hz), 7.30(1H, s), 7.39-7.45(2H, rn), 8.03(1H, d, J=8.4Hz)

Reference： [1]Patent: WO2013/162077,2013,A1 .Location in patent: Paragraph 0426

19
[ 762287-57-0 ]
[ 1562338-69-5 ]
[ 1562339-84-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In ethanol; water; for 5h;Reflux;	A mixture of <strong>[762287-57-0]4-chloro-2-methoxyphenylboronic acid</strong> (1.12 g, 6.00 mmol), Intermediate 1-3(1.94 g, 7.20 mmol), SiliaCat DPP-Pd (1.15 g, 0.30 mmol) and potassium carbonate in5 ethanol/water (1 0:1, 33 ml) was heated at reflux for 5 h. The solvent was evaporated and theresulting brown residue was partitioned between DCM and an 8% aqueous solution of K2C03. Afterseparation, the aqueous layer was extracted with DCM. The combined organic layers werewashed with brine, dried over Na2S04, filtered and concentrated to dryness in vacuo. The crudematerial was purified by flash chromatography (30 uM amine, -(CH2)3NH 2, functionalized silica gel,10 30 to 100% Et20 in heptane) to give a mixture (1.76 g) of the desired product (75%) andIntermediate 1-3 (25%). [M+H]: 376.3; 1H NMR (400 MHz, DMSO-d6) 8 7.91 (d, J=9.0 Hz, 1 H),7.71 (d, J=8.0 Hz, 1 H), 7.27 (d, J=2.0 Hz, 1 H), 7.12-7.20 (m, 2H), 5.68 (tt, J=11.0, 4.0 Hz, 1 H),3.85 (s, 3H), 1.99-2.11 (m, 2H), 1.20-1.30 (m, 8H), 1.10 (s, 6H).

Reference： [1]Patent: WO2014/28459,2014,A1 .Location in patent: Page/Page column 81; 82

20
[ 762287-57-0 ]
[ 1565836-98-7 ]
1-(2-(5-chloro-2-methoxyphenyl)-4-methyl-6-(3-phenoxyphenyl)pyrimidin-5-yl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%		Compound3p (1 g, 2.95 mmol) was reacted asdescribed in Section 2.1 to give 4pas green solid (0.417 g, 82%); Rf (20% EtOAc-Hexane) 0.65, blue spot; mp 82-84C;1H NMR (400 MHz, CDCl3) delta: 2.187 (s, 3H, -CH3), 2.607(s, 3H, -CH3), 3.825 (s, 3H, -OCH3), 6.955-6.977 (d,J=9.2 Hz, 1H, Ar-H), 7.065-7.084 (d, J=7.6 Hz, 2H, Ar-H), 7.137-7.189 (m, 3H, Ar-H),7.362-7.466 (m, 6H, Ar-H); 13CNMR (100 MHz, CDCl3) delta:22.63, 32.03, 56.4, 113.7, 118.79, 119.52, 120.48, 123.66, 123.99, 125.76, 127.41,129.97, 130.38, 130.49, 130.75, 156.40, 156.58, 158.19, 161.31, 163.61, 164.0,204.24; IR (KBr, cm-1): 2968, 2351, 1768, 1643, 1527, 1491, 1232,868, 711. Anal.Calcd for C22H22ClN3O2:C, 70.19; H, 4.76; N, 6.30. Found: C, 70.70; H, 4.82; N, 6.49.

Reference： [1]Tetrahedron Letters,2014,vol. 55,p. 1456 - 1460

21
[ 109-04-6 ]
[ 762287-57-0 ]
[ 1584705-83-8 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 2046 - 2049

22
[ 109-04-6 ]
[ 762287-57-0 ]
[ 1584705-72-5 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 2046 - 2049

23
[ 762287-57-0 ]
[ 1613711-58-2 ]
[ 1613711-66-2 ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In acetonitrile; at 85℃; for 4.25h;Inert atmosphere; Sealed tube;	Step 1:To a stirred solution of compound 8 (150mg, 0.387mmo1) and 33 (72mg, 0.387mmo1) in acetonitrile (5mL), degassed and purged with nitrogen for 10mm, was added Cs2CO3 (253mg, 0.775mmo1) and Pd(dppf)C12 (16mg, 0.0193mmo1). The resulting RIVI was degassed, purged with nitrogen again for 15mm and was heated to 85C for 4hr in a sealed tube. After completion of the reaction was cooled to rt and diluted with chloroform and filtered through celite bed. The organic layer was completely distilled off to get the crude compound 34. The crude was passed through 100-200 mesh silica gel eluting the pure compound at 7-8% ethyl aceate in hexane as off white colored solid 34.

Reference： [1]Patent: WO2014/93383,2014,A1 .Location in patent: Paragraph 00146

24
[ 762287-57-0 ]
[ 1613711-67-3 ]

Reference： [1]Patent: WO2014/93383,2014,A1

25
[ 762287-57-0 ]
[ 1613708-95-4 ]

Reference： [1]Patent: WO2014/93383,2014,A1

26
4-chloro-3-iodo-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridine [ No CAS ]
[ 762287-57-0 ]
[ 1613711-84-4 ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In acetonitrile; at 85℃; for 4.25h;Inert atmosphere; Sealed tube;	Step 1:To a stirred solution of 16 (150mg, 0.347mmo1) and 79 (64.3mg, 0.347mmo1) in acetonitrile (7mL), degassed and purged with nitrogen for 10mm, was added cesium carbonate (228mg, 0.694mmo1) and Pd(dppf)C12 (14.1mg, 0.Ol73mmol), again degassed and purged with nitrogen again for 15mm and the RM was heated to 85C for 4hr in a sealed tube. After completion of the reaction the RIVI was cooled to rt and diluted with chloroform and filtered through celite bed. The organic layer was completely distilled off to get the crude, which was passed through 100-200 mesh silica gel eluting the pure compound at 7-8% ethyl aceate in hexane as off white colored solid compound 80.

Reference： [1]Patent: WO2014/93383,2014,A1 .Location in patent: Paragraph 00176

27
[ 762287-57-0 ]
[ 1620515-75-4 ]
[ 1620516-01-9 ]

Yield	Reaction Conditions	Operation in experiment
89%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 80℃; for 18h;Inert atmosphere;	Step 1: 5-(4-Chloro-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine Nitrogen was bubbled through a stirred solution of 5-bromo-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine [Intermediate 4] (1 g, 3.00 mmol) and <strong>[762287-57-0](4-chloro-2-methoxyphenyl)boronic acid</strong> (0.615 g, 3.30 mmol) in dioxane (20 mL). To this mixture was added Pd(PPh3)4 (0.173 g, 0.150 mmol) followed by a solution of Na2CO3 (0.954 g, 9.00 mmol) in water (5 mL). The reaction was heated at 80 C. for 18 hours. The reaction mixture was cooled to RT, diluted with EtOAc (150 mL) and washed with water (100 mL). The organic phase was separated, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to afford the crude product as a dark red/brown oil which solidified on standing. The crude material was purified by flash chromatography using an 80 g silica cartridge running a gradient of [2M NH3 in MeOH]/DCM to afford the title compound as an off-white solid (1.051 g, 89% yield). LC-MS: Rt 1.04 min; MS m/z 395.2 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) delta ppm 8.09 (d, J=8.59 Hz, 1H), 7.32 (d, J=2.02 Hz, 1H), 7.15 (dd, J=8.59, 2.02 Hz, 1H), 4.35 (tt, J=12.38, 3.54 Hz, 1H), 3.97 (s, 3H), 2.98 (s, 3H), 1.60 (dd, J=11.87, 3.28 Hz, 2H), 1.41 (t, J=12.13 Hz, 2H), 1.27 (s, 1H), 1.21 (s, 6H), 1.08 (s, 6H).

Reference： [1]Patent: US2014/206661,2014,A1 .Location in patent: Paragraph 0375; 0376

28
[ 762287-57-0 ]
[ 75908-67-7 ]
C₁₈H₁₅ClO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; sodium carbonate; In tetrahydrofuran; water; at 95℃;Inert atmosphere;	A suspension of compound 22c (500 mg, 2.3 mmol), compound 22d (350 mg, 1.8 mmol), Pd(dppf)2Cl2(69 mg, 0.09 mmol), and Na2CO3(0.6 g, 5.64 mmol) in THF/H2O (10: 1, 20 mL) was refluxed at 95C overnight under N2 protection. After that, the mixture was filtered, and the filtrate was washed with water (50 mL) and extracted with EtOAc (100 mL). The organic layer was washed with brine and dried over anhydrous sodium sulfate. After filtration and concentration, the residue was purified by SiO2 chromatography, eluting with petroleum ether: ethyl acetate (100/1-10/1) to afford the compound 22e (0.3 g, 48%).
48%	With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; sodium carbonate; In tetrahydrofuran; water; at 95℃;Inert atmosphere;	A suspension of compound 22c (500 mg, 2.3 mmol), compound 22d (350 mg, 1.8 mmol), Pd(dppf)2Cl2(69 mg, 0.09 mmol), and Na2CO3(0.6 g, 5.64 mmol) in THF/H2O (10: 1, 20 mL) was refluxed at 95C overnight under N2 protection. After that, the mixture was filtered, and the filtrate was washed with water (50 mL) and extracted with EtOAc (100 mL). The organic layer was washed with brine and dried over anhydrous sodium sulfate. After filtration and concentration, the residue was purified by SiO2 chromatography, eluting with petroleum ether: ethyl acetate (100/1-10/1) to afford the compound 22e (0.3 g, 48%).

Reference： [1]Patent: WO2015/94998,2015,A1 .Location in patent: Page/Page column 64; 65
[2]Patent: WO2015/89810,2015,A1 .Location in patent: Page/Page column 63; 64

29
[ 762287-57-0 ]
(P)-1-(4-bromo-5-fluoro-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide [ No CAS ]
(P)-1-(4'-chloro-2-fluoro-2',5-dimethoxy-4-biphenylyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinolinesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12.35%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; water; at 50℃; for 4h;Inert atmosphere;	A 5-mL vial containing (P)-1-(4-bromo-5-fluoro-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (90.7 mg, 0.183 mmol), <strong>[762287-57-0](4-chloro-2-methoxyphenyl)boronic acid</strong> (68.4 mg, 0.367 mmol, purchased from Combi-blocks), and 1,1'-bis(diphenylphosphino)ferrocene palladium(II)dichloride dichloromethane adduct (14.98 mg, 0.018 mmol) was flushed with N2 and subsequently charged with dioxane (0.70 mL) and Na2CO3, 1.9 M in H2O (0.23 mL). The red solution was stirred at 50 C. for 4 h. After cooling the dark red solution to rt, it was quenched with 1 N HCl and extracted thrice with EtOAc. The organic extracts were combined, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to a brown residue. Preparatory HPLC (25% to 70% MeCN/H2O with 0.1% TFA) afforded (P)-1-(4'-chloro-2-fluoro-2',5-dimethoxy-4-biphenylyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinolinesulfonamide (12.6 mg, 0.023 mmol, 12.35% yield) as an off-white amorphous solid. 1H NMR (400 MHz, DMSO-d6) delta ppm 3.68 (s, 3 H) 3.86 (s, 3 H) 6.46 (d, J=1.98 Hz, 1 H) 6.84 (t, J=8.87 Hz, 2 H) 7.18 (dd, J=8.14, 2.02 Hz, 1 H) 7.23-7.31 (m, 2 H) 7.43 (dd, J=8.81, 5.08 Hz, 2 H) 7.89 (d, J=9.01 Hz, 1 H) 8.24 (d, J=9.54 Hz, 1 H) 8.39 (d, J=2.18 Hz, 1 H) 8.74 (d, J=1.98 Hz, 1 H) 11.68 (s, 1 H). m/z (ESI) 556.1 (M+H)+.

Reference： [1]Patent: US9212182,2015,B2 .Location in patent: Page/Page column 157; 158

30
[ 762287-57-0 ]
[ 1510865-67-4 ]
tert-butyl 3-(4-chloro-2-methoxyphenyl)azetidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In 1,4-dioxane; for 18h;Inert atmosphere; Heating; Sealed tube;	General procedure: To a solution of sulfonyl chloride (1.0 equiv) in THF (0.2 M) at 0 C was added hydrazine hydrate (2.5 equiv) dropwise. The reaction mixture was stirred at 0 C until complete conversion was observed by thin-layer chromatography. The mixture was diluted with EtOAc, washed with brine, dried over Na2SO4 and solvents removed in vacuo to give sulfonylhydrazides. To a solution of sulfonylhydrazones (1.0 equiv) in MeOH (0.5 M) was added ketone (1.0 equiv). The reaction mixture was stirred at room temperature until complete conversion was observed by TLC. Solvents were removed in vacuo to give sulfonylhydrazones. Sulfonylhydrazone (0.5 mmol, 1.0 equiv), boronic acid (0.75 mmol, 1.5 equiv), and cesium carbonate (0.75 mmol, 1.5 equiv) were placed in an oven-dried tube in vacuo for 30 min. The tube was backfilled with argon followed by the addition of dry degassed 1,4-dioxane (2 mL, 0.25 M). This tube was sealed and heated to 110 C for 18 h before being cooled to room temperature, quenched with NaHCO3 (2 mL of a saturated aqueous solution), and extracted with CH2Cl2 (3 5 mL). The organic phase was dried over MgSO4, and solvents were removed in vacuo to give a residue, which was purified by flash column chromatography (10%30% EtOAc/hexane) to give the title compounds.