[ CAS No. 19393-92-1 ] {[proInfo.proName]}

Name: 19393-92-1|2-Bromo-1,3-dichlorobenzene|95%
Brand: Ambeed
SKU: A179120
Price: 9.0 USD
Availability: InStock
Rating: 92 (40 reviews)

,{[proInfo.pro_purity]}

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

DV 2D 3D

3d Animation Molecule Structure of 19393-92-1

Structure of 19393-92-1 * Storage: {[proInfo.prStorage]}

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

Search after Editing

* Storage: {[proInfo.prStorage]}

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

Quality Control of [ 19393-92-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 19393-92-1 ]

SDS Specification

Alternatived Products of [ 19393-92-1 ]

Product Details of [ 19393-92-1 ]

CAS No. :	19393-92-1	MDL No. :	MFCD00000574
Formula :	C₆H₃BrCl₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UWOIDOQAQPUVOH-UHFFFAOYSA-N
M.W :	225.90	Pubchem ID :	29568
Synonyms :

Calculated chemistry of [ 19393-92-1 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	0.0
Num. H-bond donors :	0.0
Molar Refractivity :	44.16
TPSA :	0.0 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-4.93 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.31
Log Po/w (XLOGP3) :	3.87
Log Po/w (WLOGP) :	3.76
Log Po/w (MLOGP) :	4.22
Log Po/w (SILICOS-IT) :	3.82
Consensus Log Po/w :	3.59

Druglikeness

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

Water Solubility

Log S (ESOL) :	-4.17
Solubility :	0.0152 mg/ml ; 0.0000673 mol/l
Class :	Moderately soluble
Log S (Ali) :	-3.57
Solubility :	0.0612 mg/ml ; 0.000271 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.49
Solubility :	0.00733 mg/ml ; 0.0000324 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	1.66

Safety of [ 19393-92-1 ]

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 [ 19393-92-1 ]

* 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 [ 19393-92-1 ]
Downstream synthetic route of [ 19393-92-1 ]

[ 19393-92-1 ] Synthesis Path-Upstream 1~7

1
[ 401631-85-4 ]
[ 19393-92-1 ]
[ 541-73-1 ]

Reference： [1] Synthesis, 2001, # 14, p. 2180 - 2190

2
[ 621-38-5 ]
[ 19393-92-1 ]

Reference： [1] Journal of the Chemical Society, 1901, vol. 79, p. 1303

3
[ 80026-10-4 ]
[ 19393-92-1 ]

Reference： [1] Journal of the Chemical Society, 1901, vol. 79, p. 1303

4
[ 1940-29-0 ]
[ 19393-92-1 ]

Reference： [1] Journal of the Chemical Society, 1901, vol. 79, p. 1303

5
[ 19393-92-1 ]
[ 2268-05-5 ]

Reference： [1] Synthesis, 2010, # 14, p. 2490 - 2494
[2] Angewandte Chemie - International Edition, 2010, vol. 49, # 12, p. 2215 - 2218
[3] Angewandte Chemie - International Edition, 2010, vol. 49, # 12, p. 2219 - 2222

6
[ 19393-92-1 ]
[ 62-53-3 ]
[ 15307-93-4 ]

Reference： [1] Advanced Synthesis and Catalysis, 2006, vol. 348, # 1-2, p. 23 - 39

7
[ 19393-92-1 ]
[ 73852-17-2 ]

Reference： [1] Patent: US6521666, 2003, B1,

[ 19393-92-1 ] Synthesis Path-Downstream 1~88

1
[ 19393-92-1 ]
[ 860603-32-3 ]

Reference： [1]Journal of the Indian Chemical Society,1953,vol. 30,p. 548

2
[ 10416-59-8 ]
[ 19393-92-1 ]
[ 3376-24-7 ]
[ 78935-71-4 ]

Reference： [1]Chemistry Letters,1981,p. 1049 - 1052

3
[ 19393-92-1 ]
[ 3376-24-7 ]
[ 89900-86-7 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions II,1984,p. 29 - 34

4
[ 19393-92-1 ]
[ 62-53-3 ]
[ 15307-93-4 ]

Reference： [1]Advanced Synthesis and Catalysis,2006,vol. 348,p. 23 - 39

5
C₁₅H₂₂BNO₅ [ No CAS ]
[ 19393-92-1 ]
[ 955124-60-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl acetamide; at 100℃; for 18h;	(R)- tert-huty\\ (8-(2,6-dichlorophenyl)- 2-chromanyl)rnethylcarbamate; [00169] A 1-L flask equipped with a mechanical stirrer, nitrogen inlet, a 500- mL addition funnel capped with a rubber septum, and a thermocouple, set in a acetone bath cooled with a submersible chiller, was purged with nitrogen and charged with a solution of (R>-/er/-butyl (2- chromanyl)methylcarbamate (all of the isolated material from the previous step, 0.13 mol) in dry THF (100 mL). THF (500 mL) was added to the flask. The solution was cooled to -60 0C. A solution of t-BuLi in pentane (1.6 M, titrated, 245 mL, 0.39 mol, 3.0 eq.) was placed into the addition funnel and from there it was added slowly to the solution in the flask. The temperature was maintained below -57 0C by adjusting the rate of addition, addition time was 50 min.[00170] When the addition was complete, the bath temperature was set at -60 0C, the temperature inside the flask equilibrated at -57 0C. The mixture was left overnight at that <n="68"/>temperature (18 hr). Neat triisopropyl borate (149 mL, 0.65 mol, 5.0 eq.) was placed into the addition funnel. The reaction mixture was chilled to -70 0C, and triisopropyl borate was added rapidly to the reaction mixture (exotherm, temperature rose to -52 °). The cold bath was removed, and the reaction mixture was allowed to warm to room temperature. HPLC analysis, area percent: boronic acid 92percent, borinic acid (Ar2BOH) 6percent, unknown impurity 2percent. [00171] A 2- L Erlenmeyer flask was equipped with a mechanic stirrer and a thermocouple and set in an acetone bath was charged with 1 M aq. HCl solution (520 mL). This quench solution was chilled to -5 0C (bath temperature -15 °C). The reaction mixture was transferred to the quench solution via a cannula (gauge 12). The transfer rate was adjusted to keep the temperature below 0 0C. When the addition was complete, the bath was removed and the resulting biphasic mixture was stirred at room temperature for 2 hours.[00172] The layers were separated. The organic layer was evaporated in vacuo to a thick oil. The aqueous layer was extracted with MTBE (2 x 100 mL). The extracts were combined with the residue after evaporation and the resulting solution was washed with brine (2 x 50 mL) and evaporated in vacuum to afford a semi- solid white residue (61.7 g). [00173] The residue was dissolved dimethylacetamide (DMA, 300 mL) and the solution was placed into a 1- L round bottom flask equipped with a mechanical stirrer, a thermocouple and a nitrogen line. Solid 2,6-dichlorobromobenzene (27.9 g, 0.124 mol, 0.95 eq) and potassium phosphate (83 g, 0.39 mol, 3.0 eq.) were added. The reaction flask was purged with nitrogen, then solid Pd(PPh3)4 (3.00 g, 2.6 mmol, 2 molpercent) was added. The reaction mixture was heated at 100 0C for 18 hours. The HPLC analysis at that point showed no boronic acid remaining in the mixture.[00174] The reaction mixture was allowed to cool to room temperature, then it was transferred to a mixture of 1.1 L of water and 100 mL of heptane which was mechanically stirred in a 2-L Erlenmeyer flask. The resulting mixture was stirred at room temperature for 3 hours, then the solids were filtered off and washed with heptane and water. The cake was dried on the filter, 41.1 g (76percent from the amide, 5 steps) as an off-white solid. M.p. 158-161 0C (racemate 132-136 0C).[00175] 1H NMR (400 MHz, CDCl3), delta: 7.42-7.37 (m, 2H), 7.22 (t, J = 7.1 Hz, IH), 7.13 (m, IH), 7.01-6.93 (m, 2H), 4.70 (m, IH), 4.07 (m, IH), 3.42 (ddd, J = 3.2, 7.2, 13.9 Hz, IH), 3.12 (ddd, J = 5.1, 7.4, 13.9 Hz, IH)5 2.94 (ddd, J = 6.3, 11.2, 16.7 Hz, IH), 2.84 (ddd, J = 3.2, 5.9, 16.7 Hz, IH), 1.98 (d5, J = 2.8, 13.6 Hz, IH), 1.85-1.73 (m, IH), 1.43 (s, 9H). <n="69"/>[00176] 13C NMR (100 MHz, CDCl3), delta: 156.05, 151.38, 136.48, 135.59, 135.32, 130.01,128.84, 128.55, 127.88, 127.68, 125.00, 122.29, 120.00, 79.12, 75.21, 44.38, 28.38, 24.58,24.37.[00177] HRMS (ESI+), m/z: 430.09447 (M+Na),+ calc'd for C2IH23Cl2NO3Na: 430.09472.

Reference： [1]Patent: WO2007/123941,2007,A2 .Location in patent: Page/Page column 59; 66-68

6
[ 19393-92-1 ]
[ 179897-94-0 ]
(+/-)-[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 230 (+-)-[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine The title compound was prepared (0.21 g, 5percent) following the general procedure of Example 166 as a white solid, hydrochloride salt from (5-fluoro-2-methoxyphenyl)boronic acid (3.0 g, 17.6 mmol) and <strong>[19393-92-1]2-bromo-1,3-dichlorobenzene</strong> (2.65 g, 12.0 mmol). mp 204-205° C.

Reference： [1]Patent: US2005/261347,2005,A1

7
[ 19393-92-1 ]
[ 89694-48-4 ]
[ 852122-20-4 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 263 (+-)-[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine The title compound was prepared (0.072 g, 8percent) following the general procedure of Example 166 as a white solid, hydrochloride salt from (5-chloro-2-methoxyphenyl)boronic acid (5.0 g, 26.88 mmol) and <strong>[19393-92-1]2-bromo-1,3-dichlorobenzene</strong> (12.14 g, 53.76 mmol). mp 234-236° C.

Reference： [1]Patent: US2005/261347,2005,A1

8
[ 19393-92-1 ]
2',6'-dichloro-2,3-dihydroxybiphenyl [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 5960 - 5967

9
[ 19393-92-1 ]
[ 1940-28-9 ]

Reference： [1]Journal of the American Chemical Society,2003,vol. 125,p. 7792 - 7793
[2]Synthesis,2011,p. 857 - 859
[3]Journal of Medicinal Chemistry,2017,vol. 60,p. 6451 - 6457
[4]Patent: WO2019/126759,2019,A1

10
[ 19393-92-1 ]
[ 6575-25-3 ]

Reference： [1]Organic and biomolecular chemistry,2003,vol. 1,p. 498 - 506
[2]Patent: WO2011/20615,2011,A1

11
[ 19393-92-1 ]
1-[3-(2,6-dichlorophenyl)prop-2-ynyl]-3-methylpiperidine [ No CAS ]

Reference： [1]Organic and biomolecular chemistry,2003,vol. 1,p. 498 - 506

12
[ 19393-92-1 ]
[ 405262-84-2 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2001,vol. 49,p. 1593 - 1603

13
2,6-dichlorobenzenediazonium o-benzenedisulfonimide [ No CAS ]
[ 19393-92-1 ]

Reference： [1]Synthesis,2001,p. 2180 - 2190

14
[ 19393-92-1 ]
[ 78935-71-4 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions II,1984,p. 29 - 34

15
acetic acid-(3-bromo-2,4-dichloro-anilide) [ No CAS ]
[ 19393-92-1 ]

Reference： [1]Journal of the Chemical Society,1901,vol. 79,p. 1303

16
[ 19393-92-1 ]
2-bromo-3-chloro-4,6-dinitro-aniline [ No CAS ]

Reference： [1]Journal of the Indian Chemical Society,1953,vol. 30,p. 548

17
[ 19393-92-1 ]
tetra-<i>N</i>-ethyl-2-bromo-4,6-dinitro-<i>m</i>-phenylenediamine [ No CAS ]

Reference： [1]Journal of the Indian Chemical Society,1953,vol. 30,p. 548

18
[ 19393-92-1 ]
[ 94163-55-0 ]

Reference： [1]Journal of the Indian Chemical Society,1953,vol. 30,p. 548

19
[ 19393-92-1 ]
C₆H₃Cl₃Mg [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 20℃; for 1h;	Various fluoro- and chloro-substituted aryl bromides are readily converted into the corresponding magnesium reagents at room temperature using i-PrMgCl*LiCl. The conversion is completed without 0.5-3h which is in strong contrast with the previous procedure involving i-PrMgCl or i-Pr2Mg (Scheme 2).

Reference： [1]Patent: EP1582523,2005,A1 .Location in patent: Page/Page column 6-7

20
[ 807329-97-1 ]
[ 19393-92-1 ]
C₆H₃Cl₃Mg*ClLi [ No CAS ]

Reference： [1]Patent: EP1582523,2005,A1 .Location in patent: Page/Page column 12; 15

21
[ 444721-77-1 ]
[ 19393-92-1 ]
argon [ No CAS ]
[ 865-48-5 ]
(7BR,11AS)-N-(2,6-dichlorophenyl)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indol-6-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0); In ethyl acetate; toluene;	Example 148 (7bR,11aS)-N-(2,6-dichlorophenyl)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indol-6-amine An oven-dried three-necked round bottom flask was fitted with a septa, condenser, and a stopper. The flask was charged with tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate from EXAMPLE 33, Part B (107 mg, 0.297 mmol), 2,6-dichlorobromobenzene (56 mg, 0.25 mmol), NaOt-Bu (71 mg, 0.74 mmol), and anhydrous toluene (6 mL). The solution was purged with argon at 80° C. for 25 min then cooled to room temperature. While maintaining a blanket of argon, Pd2(dba)3 (5 mg, 6 mumol), and BINAP (7 mg, 12 mumol) were added quickly. The resulting mixture was heated to 80° C. for 20 h under argon. After cooling to room temperature, the dark solution was diluted with ethyl ether (10 mL) and filtered through a pad of silica, washing with ether. The resulting solution was concentrated and the residue was chromatographed (10-12percent ethyl acetate in hexanes gradient) yielding an N-BOC intermediate (90 mg, 72percent) as a yellow foam: 1H NMR (300 MHz, CDCl3) delta 1.40 (s, 9H), 1.71-1.92 (m, 2H), 2.79-3.13 (m, 3H), 3.15-3.96 (m, 9H), 5.71 (s, 1H), 6.29-6.50 (m, 2H), 6.91-7.00 (s, 1H), 7.32 (d, 2H, J=8 Hz). This intermediate (90 mg, 0.18 mmol) was dissolved in dichloromethane (8 mL) and chilled in an ice bath. Trifluoroacetic acid (2 mL) was then added and the solution was stirred at room temperature for 2 h. The solution was made basic with 3 N NaOH, and extracted with dichloromethane. The organic layers were combined, dried over NaSO4 and concentrated to a yellow oil. An off-white solid was obtained upon trituration with ethyl acetate/hexanes yielding 58 mg (81percent) of the title compound of EXAMPLE 148. 1H NMR (300 MHz, CDCl3) delta 1.72-1.85 (m, 2H), 2.51-2.65 (m, 1H), 2.76-3.09 (m, 6H), 3.10-3.21 (m, 1H), 3.36-3.42 (m, 1H), 3.47-3.79 (m, 4H), 5.71 (s, 1H), 6.34 (s, 1H), 6.42 (s, 1H), 6.95 (t, 1H, J=8 Hz), 7.32 (d, 2H, J=8 Hz). LRMS (ES)+: 406 (M+H)+.
	tris-(dibenzylideneacetone)dipalladium(0); In ethyl acetate; toluene;	Example 148 (7bR,11aS)-N-(2,6-dichlorophenyl)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indol-6-amine An oven-dried three-necked round bottom flask was fitted with a septa, condenser, and a stopper. The flask was charged with tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate from EXAMPLE 33, Part B (107 mg, 0.297 mmol), 2,6-dichlorobromobenzene (56 mg, 0.25 mmol), NaOt-Bu (71 mg, 0.74 mmol), and anhydrous toluene (6 mL). The solution was purged with argon at 80° C. for 25 min then cooled to room temperature. While maintaining a blanket of argon, Pd2(dba)3 (5 mg, 6 mumol), and BINAP (7 mg, 12 mumol) were added quickly. The resulting mixture was heated to 80° C. for 20 h under argon. After cooling to room temperature, the dark solution was diluted with ethyl ether (10 mL) and filtered through a pad of silica, washing with ether. The resulting solution was concentrated and the residue was chromatographed (10-12percent ethyl acetate in hexanes gradient) yielding an N-BOC intermediate (90 mg, 72percent) as a yellow foam: 1H NMR (300 MHz, CDCl3) delta 1.40 (s, 9H), 1.71-1.92 (m, 2H), 2.79-3.13 (m, 3H), 3.15-3.96 (m, 9H), 5.71 (s, 1H), 6.29-6.50 (m, 2H), 6.91-7.00 (s, 1H), 7.32 (d, 2H, J=8 Hz). This intermediate (90 mg, 0.18 mmol) was dissolved in dichloromethane (8 mL) and chilled in an ice bath. Trifluoroacetic acid (2 mL) was then added and the solution was stirred at room temperature for 2 h. The solution was made basic with 3 N NaOH, and extracted with dichloromethane. The organic layers were combined, dried over NaSO4 and concentrated to a yellow oil. An off-white solid was obtained upon trituration with ethyl acetate/hexanes yielding 58 mg (81percent) of the title compound of EXAMPLE 148. 1H NMR (300 MHz, CDCl3) delta 1.72-1.85 (m, 2H), 2.51-2.65 (m, 1H), 2.76-3.09 (m, 6H), 3.10-3.21 (m, 1H), 3.36-3.42 (m, 1H), 3.47-3.79 (m, 4H), 5.71 (s, 1H), 6.34 (s, 1H), 6.42 (s, 1H), 6.95 (t, 1H, J=8 Hz), 7.32 (d, 2H, J=8 Hz). LRMS (ES)+: 406 (M+H)+.
	tris-(dibenzylideneacetone)dipalladium(0); In ethyl acetate; toluene;	Example 148 (7bR,11aS)-N-(2,6-dichlorophenyl)-1,2,7b,8,9,10,11,11a-octahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indol-6-amine An oven-dried three-necked round bottom flask was fitted with a septa, condenser, and a stopper. The flask was charged with tert-butyl (7bR,11aS)-6-amino-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate from EXAMPLE 33, Part B (107 mg, 0.297 mmol), 2,6-dichlorobromobenzene (56 mg, 0.25 mmol), NaOt-Bu (71 mg, 0.74 mmol), and anhydrous toluene (6 mL). The solution was purged with argon at 80° C. for 25 min then cooled to room temperature. While maintaining a blanket of argon, Pd2(dba)3 (5 mg, 6 mumol), and BINAP (7 mg, 12 mumol) were added quickly. The resulting mixture was heated to 80° C. for 20 h under argon. After cooling to room temperature, the dark solution was diluted with ethyl ether (10 mL) and filtered through a pad of silica, washing with ether. The resulting solution was concentrated and the residue was chromatographed (10-12percent ethyl acetate in hexanes gradient) yielding an N-BOC intermediate (90 mg, 72percent) as a yellow foam: 1H NMR (300 MHz, CDCl3) delta 1.40 (s, 9H), 1.71-1.92 (m, 2H), 2.79-3.13 (m, 3H), 3.15-3.96 (m, 9H), 5.71 (s, 1H), 6.29-6.50 (m, 2H), 6.91-7.00 (s, 1H), 7.32 (d, 2H, J=8 Hz). This intermediate (90 mg, 0.18 mmol) was dissolved in dichloromethane (8 m]L) and chilled in an ice bath. Trifluoroacetic acid (2 mL) was then added and the solution was stirred at room temperature for 2 h. The solution was made basic with 3 N NaOH, and extracted with dichloromethane. The organic layers were combined, dried over NaSO4 and concentrated to a yellow oil. An off-white solid was obtained upon trituration with ethyl acetate/hexanes yielding 58 mg (81percent) of the title compound of EXAMPLE 148. 1H NMR (300 MHz, CDCl3) delta 1.72-1.85 (m, 2H), 2.51-2.65 (m, 1H), 2.76-3.09 (m, 6H), 3.10-3.21 (m, 1H), 3.36-3.42 (m, 1H), 3.47-3.79 (m, 4H), 5.71 (s, 1H), 6.34 (s, 1H), 6.42 (s, 1H), 6.95 (t, 1H, J=8 Hz), 7.32 (d, 2H, J=8 Hz). LRMS (ES)+: 406 (M+H)+.

Reference： [1]Patent: US2002/173503,2002,A1
[2]Patent: US2004/186094,2004,A1
[3]Patent: US6849619,2005,B2

22
(MeO)3B [ No CAS ]
[ 19393-92-1 ]
[ 73852-17-2 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; In tetrahydrofuran; hexane; water;	Reference Example 1 2,6-Dichlorobenzeneboronic acid <strong>[19393-92-1]1-Bromo-2,6-dichlorobenzene</strong> (2.00 g) was dissolved in freshly distilled THF (7 mL). This solution was cooled to -78° C. and n-BuLi (8.3 mL of a 1.6M solution in hexane) was added dropwise to the cold solution under N2. The mixture was stirred for 5 min at -78° C. and (MeO)3B (2.2 mL) was added. The resulting mixture was allowed to warm to room temperature and stirred overnight. Water was added and the resulting mixture was stirred for 0.5 h, then acidified with HOAc and extracted with EtOAc. The organic layer was further washed with water and brine, dried (MgSO4) filtered and evaporated to yield 2,6-dichlorobenzeneboronic acid (1.6 g)

Reference： [1]Patent: US6521666,2003,B1

23
[ 19393-92-1 ]
[ 5720-06-9 ]
[ 852112-02-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium hydroxide;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃;	Intermediate 85 2',6'-Dichloro-2-methoxy-biphenyl: To a solution of 2,6-dichlorobenzene bromide (22.9 g, 87 mmol) and sodium hydroxide (10.1 g, 0.22 mol) in DME-water (2:1) was added 2-methoxy benzene boronic acid (20 g, 0.13 mol) at 90° C., followed by tetrakis(triphenylphosphine)-palladium (0) (5.8 g, 4.3 mmol). The reaction mixture was heated at 90° C. overnight and cooled to room temperature. The mixture was extracted with methylene chloride and washed with water. The organic solvent was removed under vacuum. Chromatography with 5percent ethyl acetate in hexanes afforded 23.57 g (93percent) of the title compound as a colorless oil. MS EI m/e 252 M+
76%	With sodium hydroxide;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 50 - 80℃; for 18.8333h;	Example 1 Preparation of 2,6-dichloro-2'-methoxybiphenyl (110):(108) (109) (110)[0097] To a 100-L reactor were charged 2-methoxybenzeneboronic acid (109) (3.51 kg, 23.1 mol, 1.37eq) and a solution of 2-bromo-l, 3-dichlorobenzene (108) in dimethoxyethane (DME, 7.64 kg, 50 w/wpercent, 16.9 mol). To this mixture was added dimethoxyethane (DME, 29 kg). The reaction contents were stirred to provide a solution, and the solution was then heated to 50 0C. To this solution was added a 4.4 M aqueous solution of sodium hydroxide (3.55 kg of NaOH in 19.0 kg of water, 5.0 eq) over a 20 minute period,Page 38 of 58Attorney Docket No. 2004658-1130 (AM102450) 426261 Iv2 EPO <DP n="40"/>maintaining a temperature of 50 + 5 0C. The reaction was then heated to 70 0C over 15 minutes, followed by addition of Pd(PPtLs)4 (0.41 kg, 0.35 mol, 2 molpercent) in one portion. The mixture was gradually heated to reflux ( to 80 0C) over a 15 minute period, and was then stirred at 80 + 20C for 18 hours. At that time, the reaction was cooled to room temperature (22 - 25 0C), the DME/water layers were separated, and the organic layer was concentrated under reduced pressure to obtain a brown oil. To this brown oil was added tert-butyl methyl ether (TBME) (15.0 kg) and water (12.0 kg). The mixture was heated to 33 + 2 0C, and recirculated with a R53-SP Zeta filter cartridge for 4 h (charcoalization). The amber-colored TBME organic layer was separated. The organic layer was washed with water (2 X 12.0 kg). TBME was removed by atmospheric distillation to obtain 16 +/- 2 L. IPA (2 X 8.0 kg) was then added to replace TBME and the IPA solution (8 +/- 2 L) was cooled to 0 to 10 0C to induce crystallization. The crystals were filtered, washed with IPA (2 x 5.0 kg), and dried at 45 0C for 20 h to obtain 3.4 kg (76percent) of compound (110). 1H NMR (300 MHz, DMSO-J6) delta 7.54 (dd, J= 0.9, 7.8 Hz, 2H), 7.46-7.37 (m, 2H), 7.15-7.02 (m, 3H).
49%	With potassium carbonate;trans-dichlorobis(tri-o-tolylphenylphosphane)palladium(II); In 1,4-dioxane; water; at 100℃; for 36h;	A mixture of l-bromo-2,6-dichlorobenzene (5.0 g, 0.022 mol), 2- methoxyphenylboronic acid (5.045 g, 0.033 mol) and potassium carbonate (7.65 g, 0.055 mol) in dioxane (130 mL) and water (13 mL) was purged with nitrogen for 20 minutes. rroeroe-dichlorobis(tri-o-tolylphosphine)palladium (II) (0.87 g, 0.0011 mol) was added and the reaction mixture heated to 100 0C for 36 hours. The cooled reaction mixture was then filtered through celite washing the filter cake with ethyl acetate. The combined organic filtrates were diluted to 500 mL by the addition of ethyl acetate, then washed with 2.0 M aqueous sodium hydroxide (2 x 350 mL), water (350 mL) and saturated brine (350 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford a yellow oil. Purification by flash chromatography using a solvent gradient of 0.5 to 2percent ethyl acetate in hexane gave 2.74 g (49percent) of 2',6'-dichloro-lJ'-biphenyl-2-yl methyl ether as a white solid. MS (EI) mlz 252 (M+).

Reference： [1]Patent: US2006/241172,2006,A1 .Location in patent: Page/Page column 57
[2]Patent: WO2008/52088,2008,A1 .Location in patent: Page/Page column 38-39
[3]Chemistry - A European Journal,2010,vol. 16,p. 4075 - 4081
[4]Patent: WO2006/116165,2006,A1 .Location in patent: Page/Page column 81

24
[ 19393-92-1 ]
[ 179897-94-0 ]
[ 885517-77-1 ]

Yield	Reaction Conditions	Operation in experiment
88 - 92%	With sodium hydroxide;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 18h;Heating / reflux;	2',6'-Dichloro-5fluoro-2-methoxy biphenyl (G-1): To a stirring 70° C. solution of 2,6-dichlorobromobenzene, boronic and palladium tetrakis in dimethoxyethane was added an aqueous solution of sodium hydroxide. The mixture was refluxed for 18 hours until less than 1percent of starting material was present by HPLC. The mixture was cooled and phases were separated. The reaction mixture was concentrated and heptanes was added. The solution was washed with water. To the product solution was added silica gel. The resulting suspension was stirred for 2 hours then filtered. The intermediate product 2',6'-dichloro-5-fluoro-2-methoxy-biphenyl in solution in heptanes was concentrated and was used directly for the bromination step. The reaction yield of the Suzuki coupling was 88-92percent.
87%	With sodium hydroxide;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃;	2',6'-Dichloro-5-fluoro-2-methoxy-biphenyl: To a solution of 2,6-dichlorobromo benzene (3.5 g, 15.7 mmol) and sodium hydroxide (3.14 g, 78.5 mmol) in DME-water (2:1) was added 5-fluoro-2-methoxy benzene boronic acid (4.0 g, 23.5 mmol) at 9O0C, followed by tetrakis(triphenylphosphine)palladium (0) (0.9 g, 0.78 mmol). The reaction mixture was heated at 9O0C overnight and cooled to room temperature. The mixture was extracted with methylene chloride and washed with water. The organic solvent was removed under vacuum. ISCO CombiFlash.(R). chromatography with 5percent ethyl acetate in hexanes afforded 2.62 g (87percent) of the product as a colorless oil. MS EI m/e 270 M+.
87%	With sodium hydroxide;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃;	To a solution of 2,6-dichlorobromobenzene (3.5 g, 15.7 mmol) and sodium hydroxide (3.14 g, 78.5 mmol) in DME-water (2:1) was added 5-fluoro-2- methoxybenzene boronic acid (4.0 g, 23.5 mmol) at 90 °C, followed by tetrakis(triphenylphosphine)palladium (0) (0.9 g, 0.78 mmol). The reaction mixture was heated at 90 0C overnight and cooled to room temperature. The mixture was extracted with methylene chloride and washed with water. The organic solvent was removed under vacuum. Chromatography with 5percent ethyl acetate in hexanes afforded 2.62 g (87percent) of 2 \\6 ' -dichloro-5 - fluoro-2-methoxybiphenyl as a colorless oil. MS (EI) m/z 270 (M+).

87%	With sodium hydroxide;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃;	Intermediate 76 2',6'-Dichloro-5-fluoro-2methoxy-biphenyl: To a solution of 2,6-dichlorobromobenzene (3.5 g, 15.7 mmol) and sodium hydroxide (3.14 g, 78.5 mmol) in DME-water (2:1) was added 5-fluoro-2-methoxybenzene boronic acid (4.0 g, 23.5 mmol) at 90° C., followed by tetrakis(triphenylphosphine)palladium (0) (0.9 g, 0.78 mmol). The reaction mixture was heated at 90° C. overnight and cooled to room temperature. The mixture was extracted with methylene chloride and washed with water. The organic solvent was removed under vacuum. Chromatography with 5percent ethyl acetate in hexanes afforded 2.62 g (87percent) of the title compound as a colorless oil. MS EI m/e 270 M+.
80%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃; for 48h;	INTERMEDIATE 12',6'-Dichloro-5-fluoro-2-methoxy-biphenyl: To a solution of 2-methoxy-5- fluorophenylboronic acid (15.1 g, 88.3 mmol) and l-bromo-2,6-dichloro benzene (11.9 g, 52.9 mmol) in degassed DME (350 mL), were added tetrakis-(triphenylphospin)- palladium(O) (3.06 g, 2.65 mmol) and 2M aqueous potassium carbonate (66.2 mL, 132.5 mmol). The reaction mixture was allowed to stir at 90 0C for 48 h, then cooled to room temperature and concentrated under vacuum. The concentrated crude was diluted with diethyl ether (150 mL), and filtered through celite. The organic layer was washed with water (2 x 150 mL) and saturated aqueous sodium chloride (100 mL), dried (sodium sulfate), and the solvent was removed in vacuo to provide a crude oil. Purification by flash column chromatography (Silica, Hexane: AcOEt 95:5) afforded 11.40 g of the title compound (80 percent yield). MS (ESI) m/z detected mass 285.9/288.3 [M + H]+; expected mass 271/273. EPO <DP n="49"/>1H NMR (300 MHz, CHLOROFORM-d) d ppm 7.39 - 7.44 (m, 2 H) 7.26 (dd, 1 H) 7.12 (ddd, 1 H) 6.96 (dd, 1 H) 6.90 (dd, 1 H) 3.77 (s, 3 H).
62 - 92%	With sodium hydroxide;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 60 - 80℃; for 18 - 25h;Heating / reflux;Product distribution / selectivity;	Example 1 l-Methoxy-4-fluoro-2',6'-dich.orobiphenyl [00111] To a solution of NaOH (54 g, 1.35 mol) in water (400 mL) heated to 60 °C was added dimethoxyethane (400 mL), then dichlorobromobenzene (Aldrich, 60 g, 0.267 mol) and boronic acid (50 g, 0.294 mol). To the resulting stirred emulsion, solid Pd(PPh3)4 (9.5 g, 8.2 mmol) was added and washed down with 100 mL of DME. The greenish mixture was heated at reflux (ca. 80 0C) while being stirred mechanically. The course of reaction was monitored by HPLC. After 2 hr, 9.0 g (0.053 mol) of additional boronic acid and 2.0 g (1.7 mmol) of the catalyst were added to the reaction mixture and the heating was continued for 16 hr longer. More boronic acid (5.8 g, 0.034 mol) and the catalyst (0.5 g, 0.4 mmol) were added at that point and the mixture was kept at reflux for 7 hr longer (23 hr was total reaction time). EPO <DP n="47"/>[00112] The heating was stopped and 600 mL of heptane and 300 mL of water were added. The mixture was allowed to cool to room temperature and then was filtered through Celite. The layers were separated, the organic layer was washed with water, three times with brine, dried with MgSO4 and filtered through a pad of Magnesol. The clear colorless solution was concentrated on a rotary evaporator to a colorless oil (weight 72 g). The oil was triturated with 120 mL of heptane which caused crystallization of a white solid. The mixture was left in a refrigerator overnight, the separated crystals were filtered and dried in air. Yield 51 g, 93percent pure. The major impurity was determined to be the homo-coupling product 13. Additional recrystallization of the material from heptane gave crystals of 98percent purity. Yield 45 g (62percent) as white crystals.; [00127] To a stirring 7O0C solution of 2,6-dichlorobromobenzene (0.6 Kg, 2.656 mol), boronic acid (0.588 Kg, 3.46 mol) and palladium tetrakis triphenylphosphine (0.0614 Kg, 0.053 mol) in dimethoxyethane (6.0 L) is added an aqueous solution of sodium hydroxide (0.53 Kg, 13.25 mol in 3.0 Kg water). The mixture is refluxed for 18 hours. The mixture is cooled and phases are separated. The reaction mixture is concentrated and heptanes is added. The solution is washed with water. To the product solution is added silica gel The suspension is stirred for 2 hours then filtered. The intermediate product 2',6'-dichloro-5- fluoro-2-methoxy-biphenyl in solution in heptanes is concentrated and is used directly for the bromination step. The reaction yield of the Suzuki coupling is (88-92percent).

Reference： [1]Patent: US2007/255065,2007,A1 .Location in patent: Page/Page column 45; 46
[2]Patent: WO2008/52075,2008,A2 .Location in patent: Page/Page column 93
[3]Patent: WO2006/116165,2006,A1 .Location in patent: Page/Page column 95
[4]Patent: US2006/241172,2006,A1 .Location in patent: Page/Page column 38; 56
[5]Patent: WO2008/52078,2008,A2 .Location in patent: Page/Page column 47-48; 55
[6]Patent: WO2006/47228,2006,A1 .Location in patent: Page/Page column 45-46; 52
[7]Organic process research and development,2010,vol. 14,p. 1438 - 1447

25
[ 19393-92-1 ]
[ 57260-71-6 ]
4-(2,6-dichloro-phenyl)-piperazine-1-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 100℃; for 0.5h;Microwave irradiation;	EXAMPLE 20; Example 2OA. l^te-chlorophenvDsulfonyl'M-^.-dichlorophenvDpiperazine; Step 2OA; 2,6-dichlorobromobenzene (2.26g, 10 mmole), N-Boc-piperazine (2.05g, 11 mmole), Pd2(dba)3 (92mg, 1 molpercent), BINAP (187mg, 3 molpercent), and sodium tert-butoxide (1.15g, 12 mmole) were charged in a microwave vessel. The vessel was capped, purged with nitrogen, and 2OmL toluene added. The reaction mixture was heated to 1100C for 30 minutes in the microwave and then the mixture was filtered through celite, rinsing with EtOAc. The filtrate was evaporated and then filtered through a pad of silica gel, eluting with dichloromethane. Evaporation gave crude 4-(2,6-Dichloro-phenyl)-piperazine-l-carboxylic acid tert-butyl ester as an orange oil that was taken on to the next step without further purification.

Reference： [1]Patent: WO2007/92435,2007,A2 .Location in patent: Page/Page column 168-169

26
[ 19393-92-1 ]
[ 997-50-2 ]
[ 2767-54-6 ]

Reference： [1]Synthesis,
Synthesis,1971,p. 537 - 538

27
[ 19393-92-1 ]
[ 34635-91-1 ]
[ 2767-54-6 ]

Reference： [1]Synthesis,
Synthesis,1971,p. 537 - 538

28
[ 19393-92-1 ]
[ 10290-98-9 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of l-bromo-2,6-dichlorobenzene 15 (21.2 g, 94.0 mmol) in THF (100 mL) at -78 0C was added n-BuLi (48.9 mL, 78.2 mmol, 1.6 M in hexanes). The reaction mixture was stirred at -78 0C for 2 hours. Sulfur dioxide was bubbled into the mixture for 15 min. The yellow solution was stirred overnight at 40C, during which a colorless precipitate formed. The reaction was warmed to rt, hexanes was added and the sulfinic salt was filtered. The salt was dissolved in water (250 mL) and sodium acetate (16.0 g, 196 mmol) was added. The solution was cooled to 10 0C and hydroxylamine-0-sulfonic acid (H g, 98 mmol) was added. The ice-water bath was removed and a white product precipitated out within minutes. The reaction was stirred for 3 hours. The reaction was extracted with EtOAc <n="29"/>(3x) and the combined organic layers were washed with 5percent NaHCO3. Dry over Na2SO4, filter and concentrate to afford the sulfonamide 16 a colorless solid. Use crude in next reaction.

Reference： [1]Patent: WO2008/116304,2008,A1 .Location in patent: Page/Page column 27-28

29
[ 1001076-50-1 ]
[ 19393-92-1 ]
C₂₃H₂₆Cl₂N₂OS [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 2574 - 2579

30
[ 1066-35-9 ]
[ 19393-92-1 ]
[ 1034709-97-1 ]

Reference： [1]Journal of the American Chemical Society,2009,vol. 131,p. 3104 - 3118

31
[ 19393-92-1 ]
[ 1159281-90-9 ]
[ 1159281-88-5 ]

Yield	Reaction Conditions	Operation in experiment
33%	With potassium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 160℃; for 0.5h;Microwave irradiation;	1-[2-(2,6-Dichlorophenylamino) phenyl]-lambda/-[2-(2-hydroxy- ethoxy)ethyl]methanesulfonamide (I)To a stirred solution of 1-(2-aminophenyl)-lambda/-[2-(2-hydroxyethoxy)ethyl]- methanesulfonamide (100mg, 0.37mmol), 1 ,3-dichloro-2-bromobenzene (103mg, 0.46mmol), K2CO3 (126mg, 0.99mmol) and XantPhos (21 mg, 0.04mmol) in 1 ,4-dioxane (2ml) under nitrogen in a microwave tube was added Pd2dba3 (17mg, 0.019mmol) in one portion and the tube sealed. The reaction was heated with stirring in a microwave at 16O0C for 30 minutes. The reaction was cooled before filtering through celite. The crude reaction mixture was purified by column chromatography eluting with ethyl acetate:hexane to afford 1-[2-(2,6-Dichlorophenylamino)phenyl]-lambda/-[2-(2-hydroxyethoxy)- <n="54"/>ethyl]methanesulfonamide as product (50.5mg, 33percent); Rf (ethyl acetate:hexane 1 :1 ) 0.11 ; deltaH (400 MHz, CDCI3) 7.34 (3H, m), 7.23 (1 H, t), 7.19 (1 H, s), 7.02 (2H, m), 6.60 (1 H, d), 5.70 (1 H, s), 4.56 (2H, s), 3.70 (2H, s), 3.56 (4H, m), 3.29 (2H, dt) and 2.83 (1 H, s); LCMS Rt=3.97 min, m/z (ES+) 441 (M+Na).
33%	With potassium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 160℃; for 0.5h;Inert atmosphere; microwave irradiation; sealed tube;	To a stirred solution of 1-(2-aminophenyl)-N-[2-(2-hydroxyethoxy)ethyl]-methanesulfonamide (100 mg, 0.37 mmol), 1,3-dichloro-2-bromobenzene (103 mg, 0.46 mmol), K2CO3 (126 mg, 0.99 mmol) and XantPhos (21 mg, 0.04 mmol) in 1,4-dioxane (2 ml) under nitrogen in a microwave tube was added Pd2dba3 (17 mg, 0.019 mmol) in one portion and the tube sealed.The reaction was heated with stirring in a microwave at 160° C. for 30 minutes.The reaction was cooled before filtering through celite.The crude reaction mixture was purified by column chromatography eluting with ethyl acetate:hexane to afford 1-[2-(2,6-Dichlorophenylamino)phenyl]-N-[2-(2-hydroxyethoxy)-ethyl]methanesulfonamide as product (50.5 mg, 33percent); Rf (ethyl acetate:hexane 1:1) 0.11; deltaH (400 MHz, CDCl3) 7.34 (3H, m), 7.23 (1H, t), 7.19 (1H, s), 7.02 (2H, m), 6.60 (1H, d), 5.70 (1H, s), 4.56 (2H, s), 3.70 (2H, s), 3.56 (4H, m), 3.29 (2H, dt) and 2.83 (1H, s); LCMS Rt=3.97 min, m/z (ES+) 441 (M+Na).

Reference： [1]Patent: WO2009/71947,2009,A2 .Location in patent: Page/Page column 51-52
[2]Patent: US2012/65270,2012,A1 .Location in patent: Page/Page column 16

32
[ 19393-92-1 ]
[ 13331-27-6 ]
[ 851534-93-5 ]

Yield	Reaction Conditions	Operation in experiment
		0.14 g of tetrakistriphenylphosphine palladium was added at room temperature to a solution having 0.9 g of 1-brom-2, 6-dichlorobenzene dissolved in 50 ml of toluene, followed by stirring for 10 minutes. 0.8 g of 3- nitrophenyl boronic acid, 5 ml of ethanol and 4.2 ml of a . 2M sodium carbonate aqueous solution were added thereto, and the reaction system was flushed with nitrogen, followed by stirring for 15 hours under reflux under heating. After cooling, the reaction solution was filtered through celite, followed by washing thoroughly with ethyl acetate from above. Cold water was added to the filtrate, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel (Silica gel 60N; spherical and neutral, manufactured. by Kanto Kagaku) column chromatography to obtain 0.98 g of 3- (2, 6- dichlorophenyl) nitrobenzene as an oily substrate. Further, NMR of this compound was as follows. 1H-NMR 5 (ppm) 7.30 (t, lH ; J =8. 1 Hz), 7.42 (d, 2H; J =8. 1 Hz), 7.61 (d, lH ; J =7.8 Hz), 7.65 (t, lH; J =7. 8 Hz), 8.18 (s, lH), 8. 29 (d, lH ; J =7.8 Hz)

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 7410 - 7424
[2]Patent: WO2005/44007,2005,A1 .Location in patent: Page/Page column 48-49

33
[ 19393-92-1 ]
[ 124-63-0 ]
[ 15448-47-2 ]
[ 1188412-82-9 ]

Yield	Reaction Conditions	Operation in experiment
		To a cooled (-78 °C) solution of 2,6-dichlorobromobenzene (14 a) (970 mg, 4.3 mmol) in THF (10.0 mL) was slowly added n-BuLi (1.75 mL, 2.5 M solution in hexane). After 20 minutes, a solution of (R)-(+)-propylene oxide (lib) (250 mg, 4.3 mmol) was added. The resulting solution was slowly brought to room temperature and stirred for 7 h. The reaction was cooled to 0 °C and methanesulfonyl chloride (0.5 g, 4.3 <n="98"/>mmol) was slowly added and stirred at room temperature for over night. The reaction mixture was diluted with water (15 mL) and extracted with ethyl acetate (3x 10 mL). The extracts were dried and concentrated to get crude product (15a) that was stirred with sodium azide (1.4 g, 21.5 mmol) in DMF (15 mL) at 70 °C for 3 h. The reaction mixture was diluted with cold water (30 mL) and extracted with ethyl acetate (2x 25 mL). The combined extract was washed with water (2x20 mL), dried and concentrated to get crude azide that was purified by silica gel column using 10 percent ethyl acetate/hexane to get pure azide. To a 0°C cooled solution of SnCl2 (1.5 g, 7.9 mmol) was added a solution of crude azide in methanol (3 mL). After stirring at room temperature for 7 h, and solvent was removed under reduced pressure. To the residue were added DCM (20 mL) and saturated KOH solution (PH -12). The aqueous layer was extracted with DCM (3x 20 mL). The combined extracts were dried and concentrated at room temperature to get crude (lS)-2-(2,6-dichloro-phenyl)-l -methyl- 1-ehtylamine (16a) (500 mg) ESI-MS mlz 204.6 (M++ 1). The obtained amine was used for next reaction without further purification.

Reference： [1]Patent: WO2009/117097,2009,A1 .Location in patent: Page/Page column 96-97

34
[ 56-18-8 ]
[ 19393-92-1 ]
[ 1207685-52-6 ]

Reference： [1]Russian Journal of Organic Chemistry,2009,vol. 45,p. 1353 - 1364

35
[ 19393-92-1 ]
[ 929-59-9 ]
[ 1207685-66-2 ]

Reference： [1]Russian Journal of Organic Chemistry,2009,vol. 45,p. 1353 - 1364

36
[ 19393-92-1 ]
[ 929-59-9 ]
N,N'-[2,2'-(ethane-1,2-diylbisoxy)bis(ethane-2,1-diyl)]bis(2,6-dichloroaniline) [ No CAS ]

Reference： [1]Russian Journal of Organic Chemistry,2009,vol. 45,p. 1353 - 1364

37
[ 19393-92-1 ]
[ 4605-14-5 ]
[ 1207685-60-6 ]
[ 1207685-61-7 ]

Reference： [1]Russian Journal of Organic Chemistry,2009,vol. 45,p. 1353 - 1364

38
[ 19393-92-1 ]
[ 7300-34-7 ]
[ 1207685-68-4 ]

Reference： [1]Russian Journal of Organic Chemistry,2009,vol. 45,p. 1353 - 1364

39
[ 19393-92-1 ]
[ 4246-51-9 ]
[ 1207685-45-7 ]

Reference： [1]Russian Journal of Organic Chemistry,2009,vol. 45,p. 1353 - 1364

40
[ 19393-92-1 ]
[ 4246-51-9 ]
[ 1207685-46-8 ]

Reference： [1]Russian Journal of Organic Chemistry,2009,vol. 45,p. 1353 - 1364

41
[ 19393-92-1 ]
[ 10563-26-5 ]
[ 1207685-44-6 ]

Reference： [1]Russian Journal of Organic Chemistry,2009,vol. 45,p. 1353 - 1364

42
[ 19393-92-1 ]
[ 111-40-0 ]
[ 1207685-51-5 ]

Reference： [1]Russian Journal of Organic Chemistry,2009,vol. 45,p. 1353 - 1364

43
[ 19393-92-1 ]
C₆H₃Cl₂O₂S^(1-)*Li⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of l-bromo-2,6-dichlorobenzene (4.34 g, 19.2 mmol) in THF (20 mL) at -78 0C was added n-BuLi (1.6 M in hexanes, 10.0 mL, 16.0 mmol). The reaction mixture (precipitate formed with time) was stirred at -78 0C for 4 hours. Sulfur dioxide was then bubbled into the mixture for 15 min. The yellow solution was warmed to RT, during which time a colorless precipitate formed. After 30 min at RT, hexane was added and the sulfinic salt was removed by filtration. The salt was dissolved in water (50 mL) and sodium acetate (3.28 g, 40.0 mmol) was added. The solution was cooled to 10 0C and hydroxylamine-O-sulfonic acid (2.26 g, 20.0 mmol) was added. The ice-water bath was removed, and a white product precipitated out within minutes. The reaction was stirred at RT overnight. The reaction was extracted with EtOAc (3 x 50 mL), and the combined organic layers were washed with 5percent NaHCO3(aq) (50 mL) and brine (50 mL), then dried (Na2SO4) and concentrated in vacuo to provide 2.66 g (11.8 mmol, 74percent) of the sulfonamide (RE6b) as a white solid.

Reference： [1]Patent: WO2010/34110,2010,A1 .Location in patent: Page/Page column 38; 55-56; 65-66

44
[ 19393-92-1 ]
[ 411235-57-9 ]
[ 1227417-84-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 110℃;	Example 18; Part A; A reaction mixture of <strong>[19393-92-1]2-bromo-1,3-dichlorobenzene</strong> (1.13 g, 5 mmol), cyclopropyl boronic acid (0.86 g, 10 mmol), tetrakis(triphenylphosphine)palladium (0.35 g, 0.3 mmol) and tripotassium phosphate (2.12 g, 10 mmol) in dioxane (6 mL) was stirred at 110 0C for overnight. The reaction mixture was filtered. The filtrate was concentrated. The residue was purified by chromatography. Elution with 10percent DCM in hexane gave compound 18-1 as a light yellow oil (0.85 g, 91percent yield). 1H NMR (400 MHz, CDCI3) delta 7.26 (d, J = 8.4 Hz, 2H), 7.07 (dt, J = 0.8, 8.8 Hz, 1 H), 1.82-1.72 (m, 1 H), 1.18-1.11 (m, 2H), 0.81-0.74 (m, 2H).

Reference： [1]Patent: WO2010/56631,2010,A1 .Location in patent: Page/Page column 118-119

45
cyclobutylzinc(II) bromide [ No CAS ]
[ 19393-92-1 ]
[ 1227417-91-5 ]

Yield	Reaction Conditions	Operation in experiment
77%	dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; In tetrahydrofuran; at 65℃;Inert atmosphere;	Example 26; STEP A; A reaction mixture of <strong>[19393-92-1]2-bromo-1,3-dichlorobenzene</strong> (452 mg, 2 mmol), palladium acetate (22.4 mg, 0.1 mmol), S-Phos (61.5 mg, 0.15 mmol) and cyclobutylzinc bromide in THF solution (0.5 M, 4 mL) was stirred at 65 °C under an atmosphere of argon for overnight. The reaction mixture was diluted with EtOAc, and concentrated. The residue was purified by chromatography. Elution with 10percent DCM in hexane gave compound 26-1 as clear oil (0.31 g, 77percent yield). 1H NMR (400 MHz, CDCI3) delta 7.24 (d, J = 8.0 Hz, 2H), 7.01 (t, J = 8.0 Hz, 1H), 4.25 (quintet, J = 9.5 Hz, 1 H), 2.86-2.74 (m, 2H), 2.42-2.30 (m, 2H), 2.05-1.90 (m, 2H).

Reference： [1]Patent: WO2010/56631,2010,A1 .Location in patent: Page/Page column 129

46
[ 19393-92-1 ]
C₁₁H₉BrN₂O₂ [ No CAS ]
5-(benzyloxy)-4-bromo-2-(2,6-dichlorophenyl)pyridazin-3(2H)-one [ No CAS ]