[ CAS No. 657408-07-6 ] {[proInfo.proName]}

Name: 657408-07-6|Dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine|98%
Brand: Ambeed
SKU: A117430
Price: 13.0 USD
Availability: InStock
Rating: 97 (27 reviews)

,{[proInfo.pro_purity]}

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

2D 3D

Structure of 657408-07-6 * 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 [ 657408-07-6 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 657408-07-6 ]

SDS Specification

Alternatived Products of [ 657408-07-6 ]

Product Details of [ 657408-07-6 ]

CAS No. :	657408-07-6	MDL No. :	MFCD05861611
Formula :	C₂₆H₃₅O₂P	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VNFWTIYUKDMAOP-UHFFFAOYSA-N
M.W :	410.53	Pubchem ID :	11269872
Synonyms :

Calculated chemistry of [ 657408-07-6 ]

Physicochemical Properties

Num. heavy atoms :	29
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.54
Num. rotatable bonds :	6
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	126.99
TPSA :	32.05 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-4.06 cm/s

Lipophilicity

Log Po/w (iLOGP) :	4.6
Log Po/w (XLOGP3) :	6.68
Log Po/w (WLOGP) :	7.14
Log Po/w (MLOGP) :	5.28
Log Po/w (SILICOS-IT) :	7.31
Consensus Log Po/w :	6.2

Druglikeness

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

Water Solubility

Log S (ESOL) :	-6.5
Solubility :	0.000129 mg/ml ; 0.000000313 mol/l
Class :	Poorly soluble
Log S (Ali) :	-7.16
Solubility :	0.0000287 mg/ml ; 0.0000000698 mol/l
Class :	Poorly soluble
Log S (SILICOS-IT) :	-8.06
Solubility :	0.00000353 mg/ml ; 0.0000000086 mol/l
Class :	Poorly soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	4.47

Safety of [ 657408-07-6 ]

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 [ 657408-07-6 ]

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

Upstream synthesis route of [ 657408-07-6 ]
Downstream synthetic route of [ 657408-07-6 ]

[ 657408-07-6 ] Synthesis Path-Upstream 1~14

1
[ 16523-54-9 ]
[ 755017-61-9 ]
[ 657408-07-6 ]

Reference： [1] Angewandte Chemie - International Edition, 2009, vol. 48, # 32, p. 5841 - 5844
[2] Journal of the American Chemical Society, 2005, vol. 127, # 13, p. 4685 - 4696

2
[ 694-80-4 ]
[ 151-10-0 ]
[ 16523-54-9 ]
[ 657408-07-6 ]

Yield	Reaction Conditions	Operation in experiment
36%	Stage #1: With n-butyllithium In tetrahydrofuran at 0 - 20℃; for 3.5 h; Stage #2: at 0℃; for 0.5 h;	To a solution of 1,3-dimethoxybenzene (2 ml, 15.30 mmol) in anhydrous THF (35 ml) at 0° C., nBuLi (6.2 ml, 15.50 mmol) is added to the dropping funnel for 5 min. The reaction medium is stirred at room temperature for 3.5 h, then 2-bromochlorobenzene (1.6 ml, 13.70 mmol) is added by syringe, dropwise, at 0° C., for 30 min. After 15 min of stirring, the reaction medium is cooled to -78° C. and nBuLi (6.20 ml, 15.50 mmol) is added to the dropping funnel dropwise for 5 min. After 30 min, chlorodicyclohexylphosphine (3.03 ml, 13.70 mmol) is added. The reaction medium is maintained at -78° C. for 1 h, under rapid stirring (mechanical stirring). After returning to room temperature, the precipitate obtained is filtered on a fritted disc containing silica topped with a layer of cellulose acetate, with 600 ml ethyl acetate. The solvents are evaporated with a rotary evaporator, and the orange oil obtained is recrystallized in acetone to obtain S-Phos ligand in the form of white crystals with a yield of 36percent (1.22 g, 2.97 mmol). MP: 163-165° C. (Lit. MP 162.0-162.5° C.); TLC: (AcOEt/cyclohexane 10/90). R_f=0.65; ¹H-NMR (CDCl₃): δ=0.99-1.26 (m, 10H, H(Cy)), 1.60-1.77 (m, 12H, H(Cy)), 3.67 (s, 6H, Me), 6.58 (d, 2H, J=8.2 Hz, H_3' and H_5'), 7.15-7.18 (m, 1H, H(Ar)), 7.18-7.42 (m, 3H, H(Ar)), 7.57 (d, 1H, J=7.4 Hz, H(Ar)) ppm; ¹³C-NMR (CDCl₃): δ=26.5, 27.3, 27.4, 27.6, 29.0, 29.1, 29.8, 30.1, 33.8, 34.0 (C(Cy)), 55.3 (Cb), 103.1 (Ca), 126.2, 128.2, 128.8 (C_3', C_4', C_5'), 130.9, 131.00, 132.4, 135.8 (C₃, C₄, C₅, C₆), 135.8, 136.1, 142.7, 143.1, 157.4 (C_2', C_6') ppm; IR (KBr): υ=3000, 2923, 2851, 1588, 1471, 1442, 1428, 1108 cm^-1.

Reference： [1] Patent: US2011/184059, 2011, A1, . Location in patent: Page/Page column 9

3
[ 1380028-15-8 ]
[ 16523-54-9 ]
[ 657408-07-6 ]

Reference： [1] European Journal of Organic Chemistry, 2012, # 11, p. 2127 - 2131

4
[ 694-80-4 ]
[ 657408-07-6 ]

Reference： [1] Journal of the American Chemical Society, 2005, vol. 127, # 13, p. 4685 - 4696

5
[ 23112-96-1 ]
[ 95-50-1 ]
[ 657408-07-6 ]

Reference： [1] European Journal of Organic Chemistry, 2012, # 11, p. 2127 - 2131

6
[ 151-10-0 ]
[ 657408-07-6 ]

Reference： [1] Journal of the American Chemical Society, 2014, vol. 136, # 24, p. 8568 - 8576

7
[ 108-90-7 ]
[ 657408-07-6 ]

Reference： [1] Journal of the American Chemical Society, 2014, vol. 136, # 24, p. 8568 - 8576

8
[ 13732-86-0 ]
[ 16523-54-9 ]
[ 657408-07-6 ]

Reference： [1] Journal of the American Chemical Society, 2014, vol. 136, # 24, p. 8568 - 8576

9
[ 657408-07-6 ]
[ 1251041-55-0 ]
[ 98-80-6 ]
[ 800402-12-4 ]

Reference： [1] Patent: US2012/61654, 2012, A1,

10
[ 657408-07-6 ]
[ 474688-76-1 ]
[ 73183-34-3 ]
[ 624744-67-8 ]

Yield	Reaction Conditions	Operation in experiment
73.2%	With nitrogen; potassium acetate In 1,4-dioxane; ethyl acetate	Example 1 Synthesis of Compound 1 Synthesis of 2-(9,10-di(naphthalen-2-yl)anthracen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane. 2-bromo-9,10-di(naphthalen-2-yl)anthracene (4.75 g, 9.32 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (3.08 g, 12.12 mmol), potassium acetate (1.830 g, 18.65 mmol) and dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (0.153 g, 0.373 mmol) were mixed in 400 mL of dioxane. The mixture was bubbled with nitrogen for 20 minutes. Pd₂(dba)₃ (0.085 g, 0.093 mmol) was added. The reaction was heated up to 90° C. overnight. The reaction was stopped and filtered through Celite. Solvent was evaporated, coated on Celite and a column was run with 10percent ethyl acetate and hexanes. The solid was then recrystallized from 100 mL of ethanol. Yellowish solid 2-(9,10-di(naphthalen-2-yl)anthracen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.8 g, 6.83 mmol, 73.2percent yield) was collected by filtration.

Reference： [1] Patent: US2012/187381, 2012, A1,

11
[ 657408-07-6 ]
[ 13078-80-3 ]
[ 1028206-58-7 ]

Reference： [1] Journal of the American Chemical Society, 2008, vol. 130, # 21, p. 6686 - 6687

12
[ 657408-07-6 ]
[ 13078-80-3 ]
[ 14267-08-4 ]
[ 917-54-4 ]
[ 1028206-58-7 ]

Reference： [1] Journal of the American Chemical Society, 2008, vol. 130, # 21, p. 6686 - 6687

13
[ 657408-07-6 ]
[ 98-80-6 ]
[ 1221398-11-3 ]

Reference： [1] Patent: US2012/61654, 2012, A1,

14
[ 657408-07-6 ]
[ 3375-31-3 ]
[ 90-41-5 ]
[ 1375325-64-6 ]

Reference： [1] Organic and Biomolecular Chemistry, 2016, vol. 14, # 6, p. 1969 - 1981

[ 657408-07-6 ] Synthesis Path-Downstream 1~88

1
[ 16523-54-9 ]
[ 755017-61-9 ]
[ 657408-07-6 ]

Reference： [1]Angewandte Chemie - International Edition,2009,vol. 48,p. 5841 - 5844
[2]Journal of the American Chemical Society,2005,vol. 127,p. 4685 - 4696

2
[ 657408-07-6 ]
3-(2-dicyclohexylphosphanylphenyl)-2,4-dimethoxy-benzenesulfonic acid [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2005,vol. 44,p. 6173 - 6177

3
[ 657408-07-6 ]
(2’,6’-dimethoxy-[1,1’-biphenyl]-2-yl)dicyclohexylphosphine oxide [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2007,vol. 129,p. 5096 - 5101
[2]Chemistry - A European Journal,2017,vol. 23,p. 14434 - 14438

4
[ 694-80-4 ]
[ 657408-07-6 ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 4685 - 4696

5
[ 151-10-0 ]
4-methoxy-<i>trans</i>(?)-cinnamic acid [ No CAS ]
[ 657408-07-6 ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 4685 - 4696

6
[ 657408-07-6 ]
sodium 2'‐(dicyclohexylphosphaneyl)‐2,6‐diisopropyl‐[1,1'‐biphenyl]‐3‐sulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%		To an oven-dried 25 mL round bottom flask equipped with a Teflon-coated magnetic stir bar and rubber septum was added 2-dicyclohexylphosphino-2'6'dimethoxybiphenyl (5.13 g, 12.5 mmol) and CH2Cl2 (5 mL). The solution was cooled to 0 C. using an ice/water bath and then concentrated H2SO4 (32.5 mL, 625 mmol) was added dropwise. The solution slowly turned yellow in color. The solution was heated to 40 C. in a preheated oil bath and was allowed stir for 24 h. At this time it was cooled to 0 C. using an ice/water bath and crushed ice (50 g) was added. The solution turned cloudy and white in color. An aqueous solution of NaOH (6.0 M, 200 mL) was then added dropwise to the cooled solution until it became neutral (pH 7.0 as judged by pH paper). The aqueous solution was extracted with CH2Cl2 (3×300 mL) and concentrated under reduced pressure to give a light yellow solid. The crude material was then dissolved in a minimum amount of cold methanol (20 mL), filtered and concentrated (this cycle was repeated) to give sodium 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl-3'-sulfonate (2) as a light yellow solid (6.35 g, 99%). Mp=165 C. (turned red, dec.) 1H NMR (400 MHz, CD3OD) delta: 7.88 (d, 1H, J=8.8 Hz), 7.60 (m, 1H), 7.36 (m, 2H), 7.22 (m, 1H), 6.76 (d, 1H, J=8.8 Hz) 3.70 (s, 3H), 3.39 (s, 3H), 1.14-2.01 (m, 22H). 13C NMR (125 MHz, CD3OD) delta: 161.3, 157.1, 143.3, 142.9, 137.9, 137.8, 133.7, 133.6, 133.3, 133.2, 131.9, 130.0, 129.3, 128.0, 127.9, 127.8, 105.9, 61.6, 56.1, 50.0, 37.0, 36.9, 34.8, 34.6, 31.7, 31.6, 31.5, 31.2, 31.0, 30.8, 30.7, 28.9, 28.8, 28.7, 28.4, 28.34, 28.31, 28.2, 27.8, 27.7. 31P NMR (162 MHz, CD3OD) delta: -8.02. IR (neat, cm-1): 3453, 2925, 2849, 1577, 1462, 1448, 1400, 1229, 1191, 1099, 1053, 736. Anal. Calcd for C26H34NaO5PS: C, 60.92; H, 6.69. Found: C, 60.40; H, 6.85. 1H NMR (d4-MeOH/D2O) is shown in FIG. 7. 31P NMR (d4-MeOH) is shown in FIG. 7.

Reference： [1]Patent: US2006/173186,2006,A1 .Location in patent: Page/Page column 18; 23; Sheet 1
[2]Journal of the American Chemical Society,2018,vol. 140,p. 13570 - 13574

7
[ 657408-07-6 ]
[ 890315-75-0 ]
[ 162101-25-9 ]
tert-butyl 2-(benzamido)-4-(2,6-difluorophenyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;palladium diacetate; In ethyl acetate; toluene;	Example 206 0.10 g of 2,6-difluorophenylboronic acid, 0.52 g of cesium carbonate, 2.4 mg of palladium acetate and 2.2 mg of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl were added to 2.5 mL of toluene solution containing 0.20 g of tert-butyl 2-(benzamido)-4-bromobenzoate at room temperature sequentially, and stirred under nitrogen atmosphere at 80C for 1 hour and 10 minutes and then heated to reflux for 1 hour. After the reaction mixture was cooled to room temperature, 2.4 mg of palladium acetate and 2.2 mg of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl were added and the resulting mixture was heated to reflux under nitrogen atmosphere for 1 hour. After the reaction mixture was cooled to room temperature, 2.4 mg of palladium acetate and 2.2 mg of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl were added and the resulting mixture was heated to reflux under nitrogen atmosphere for 1 hour. After the reaction mixture was cooled to room temperature, were added 2.0 mL of toluene, 0.04 g of 2,6-difluorophenylboronic acid, 2.4 mg of palladium acetate and 2.2 mg of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl and the resulting mixture was heated to reflux under nitrogen atmosphere for 1 hour. A saturated sodium hydrogen carbonate aqueous solution and ethyl acetate were added after the reaction mixture was cooled to room temperature. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with a saturated sodium hydrogen carbonate aqueous solution and a saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure. The obtained residue was purified with silica gel column chromatography [PSQ100B (spherical) manufactured by Fuji Silysia Chemical Ltd., eluent; hexane: ethyl acetate = 20:1] to obtain 31 mg of tert-butyl 2-(benzamido)-4-(2,6-difluorophenyl)benzoate as white solid. 1H-NMR (DMSO-d6) delta: 1.57 (9H, s), 7.26-7.36 (3H, m), 7.53-7.67 (4H, m), 7.95-8.00 (2H, m), 8.07 (1H, d, J = 8.0 Hz), 8.57-8.61 (1H, m), 11.63 (1H, s).

Reference： [1]Patent: EP1820795,2007,A1

8
[ 657408-07-6 ]
[ 890315-98-7 ]
[ 144025-03-6 ]
[ 890316-02-6 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;palladium diacetate; In hexane; di-isopropyl ether; toluene;	Referential Example 32 To 15 mL of toluene solution containing 1.5 g of tert-butyl 4-chloro-2-nitrobenzoate, 1.1 g of 2,4-difluorophenylboronic acid, 2.8 g of cesium carbonate, 27 mg of palladium acetate and 25 mg of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl were added sequentially, and the resulting mixture was heated to reflux under nitrogen atmosphere for 8 hours. After the reaction mixture was cooled to room temperature, insoluble were removed by filtration and added a saturated sodium hydrogen carbonate aqueous solution. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with 10% citric acid aqueous solution and a saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure. Hexane and diisopropyl ether were added to the obtained residue and a solid substance was separated by filtration to obtain 0.95 g of tert-butyl 4-(2,4-difluorophenyl)-2-nitrobenzoate as white solid. 1H-NMR (DMSO-d6) delta: 1.52 (9H, s), 7.26-7.31 (1H, m), 7.44-7.51 (1H, m), 7.72-7.79 (1H, m), 7.93 (1H, d, J = 7.9 Hz), 7.98 (1H, d, J = 7.9 Hz), 8.17 (1H, s).

Reference： [1]Patent: EP1820795,2007,A1

9
[ 657408-07-6 ]
[ 21264-30-2 ]
[ 848652-20-0 ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 4685 - 4696

10
[ 657408-07-6 ]
tris(dibenzylideneacetone)dipalladium ⁽⁰⁾ [ No CAS ]
Pd(dibenzylideneacetone)(C₆H₃(OCH₃)2C₆H₄P(C₆H₁₁)2) [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2004,vol. 43,p. 1871 - 1876

11
[ 657408-07-6 ]
[ 107-10-8 ]
(N,N,N',N'-tetramethylethylenediamine)dimethylpalladium(II) [ No CAS ]
[ 108-90-7 ]
[ 952090-61-8 ]

Reference： [1]Angewandte Chemie - International Edition,2007,vol. 46,p. 7232 - 7235

12
[ 657408-07-6 ]
(N,N,N',N'-tetramethylethylenediamine)dimethylpalladium(II) [ No CAS ]
[ 108-90-7 ]
[ 936951-72-3 ]

Reference： [1]Angewandte Chemie - International Edition,2007,vol. 46,p. 7232 - 7235

13
[ 657408-07-6 ]
[ 947183-38-2 ]
[ 557-21-1 ]
[ 947183-91-7 ]

Yield	Reaction Conditions	Operation in experiment
20.2%		To an argon degassed and dried flask was added (2S,3S)-2-amino-N-(2-fluoro-4-iodo-phenyl)-3-phenyl-butyramide (796 mg, 1.99 mmol), zinc cyanide (352 mg, 2.99 mmol), tetrakis-triphenylphosphine palladium (0) (116 mg, 0.1 mmol) and dry tetrahydrofuran (4 mL). After heating at 80 C. for 8 hours there was no reaction. To the cooled mixture was added 2-dicylohexylphosphino-2'-6'-dimethoxybiphenyl (42 mg, 0.1 mmol) and the reaction mixture heated again to 80 C. for 90 minutes, again no reaction occurred. To the cooled mix was added triethylamine (840 mul, 5.99 mmol) and the reaction mixture heated at 80 C. for 2 hours, again no reaction occurred. To the cooled mix was added 2-dicylohexylphosphino-2'-6'-dimethoxybiphenyl (84 mg, 0.2 mmol) and still no reaction occurred after 2 hours at 85 C. To the cooled mix was added rac-2-2'-bis(diphenylphosphino)-1-1'binaphthyl (125.6 mg, 0.2 mmol) and dry toluene (2 mL). After heating at 85 C. for 40 hours the reaction mix was dissolved in ethyl acetate (50 mL) and washed with 1.5 N aqueous potassium hydrogen sulfate solution, saturated aqueous sodium bicarbonate solution and the aqueous layers were back extracted with ethyl acetate (2×50 mL). The combined organic layers were dried over sodium sulfate and concentrated. The crude residue was purified by chromatography over silica gel gradient eluted from 5 to 15% v/v ethyl acetate in hexanes to give (2S,3S)-2-amino-N-(4-cyano-2-fluoro-phenyl)-3-phenyl-butyramide as a yellow residue after concentration of the product containing fractions (120 mg, 20.2% yield). HRMS: Obs Mass (M+H+), 531.2035. Calcd. Mass, 531.2038 for C29H28FN4O5+.

Reference： [1]Patent: US2008/207563,2008,A1 .Location in patent: Page/Page column 53-54

14
[ 657408-07-6 ]
[ 13078-80-3 ]
[ 14267-08-4 ]
[ 917-54-4 ]
[ 1028206-58-7 ]

Reference： [1]Journal of the American Chemical Society,2008,vol. 130,p. 6686 - 6687

15
[ 657408-07-6 ]
(N,N,N',N'-tetramethylethylenediamine)dimethylpalladium(II) [ No CAS ]
[ 13078-80-3 ]
[ 1028206-58-7 ]

Reference： [1]Journal of the American Chemical Society,2008,vol. 130,p. 6686 - 6687

16
[ 657408-07-6 ]
potassium phosphate [ No CAS ]
[ 1146951-49-6 ]
[ 1146950-89-1 ]
tert-butyl 4-[4-[5-(1,3-benzoxazol-2-yl)-6-(bis(tert-butoxycarbonyl)amino)-3-pyridyl]-3-cyano-pyrazol-1-yl]piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; water; ethyl acetate; Petroleum ether;	[1] Compound [1] was prepared using the following procedure: A mixture of tert-butyl N-[3-(1,3-benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]-N-tert-butoxycarbonyl-carbamate (291 mg), tert-butyl 4-(4-bromo-3-cyanopyrazol-1-yl)piperidine-1-carboxylate (150 mg), tris(dibenzylideneacetone)dipalladium (19.33 mg), dicyclohexyl-[2-(2,6-dimethoxyphenyl)phenyl]phosphine (17.34 mg) and potassium phosphate (0.084 g) in a mixture of dioxane (5 ml) and water (150 mul) was degassed. The resulting suspension was stirred and heated to 120 C. for 3 hours under argon. After the mixture was cooled to room temperature the solvent was concentrated, ethyl acetate (80 ml) and water (20 ml) were added. The organic layer was washed with brine, dried over Magnesium sulphate, filtered and evaporated under reduce pressure. The crude product was purified by flash chromatography on silica gel eluding with 20 to 75% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford tert-butyl 4-[4-[5-(1,3-benzoxazol-2-yl)-6-(bis(tert-butoxycarbonyl)amino)-3-pyridyl]-3-cyano-pyrazol-1-yl]piperidine-1-carboxylate (251 mg) as pale pink foam. The N-tert-butoxycarbonyl groups on the resultant product were removed using the procedure described for example 61.

Reference： [1]Patent: US2009/118305,2009,A1

17
[ 657408-07-6 ]
[ 109-04-6 ]
potassium phosphate [ No CAS ]
[ 16419-60-6 ]
[ 10273-89-9 ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0); In water; ethyl acetate; toluene;	Step 1. A mixture of 8.1 g (51.5 mmol) of 2-bromopyridine, 7 g (51.5 mmol) o-tolylboronic acid, 0.47 g (0.51 mmol) of Pd2(dba)3, 0.84 g (2.06 mmol) of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl and 32 g (154.5 mmol) of potassium phosphate tribasic, 100 mL of toluene and 30 mL of water was purged with nitrogen. The solution was heated to reflux for 12 hours. Upon cooling, the organic layer was separated, and dried with MgSO4. The product was separated by column chromatography using hexanes/ethyl acetate (5% ethyl acetate) as the eluent. The solvent was removed by rotary evaporation, and the product was dried under vacuum resulting in 6 g (35.5 mmol) of 2-(o-tolyl)pyridine.

Reference： [1]Patent: US2009/124805,2009,A1

18
[ 657408-07-6 ]
[ 39856-58-1 ]
potassium phosphate [ No CAS ]
[ 168618-42-6 ]
[ 1158807-07-8 ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0); In water; toluene;	Step 1. The 500 mL round-bottom flask, equipped with magnetic stirrer and reflux condenser was charged with 2-(methylthio)phenylboronic acid (9.48 g, 56 mmol), 3-amino-2-bromopyridine (7.15 g, 57 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (S-Phos, 0.92 g, 4 mol %), Pd2(dba)3 (1.02 g, 2 mol %), potassium phosphate hydrate (39 g, 3 equivalents), 100 mL of toluene. The flask was filled with nitrogen and heated to reflux under nitrogen atmosphere for 24 hours. Then the reaction was cooled down to room temperature, diluted with 500 ml of water and extracted with ethyl acetate (5*40 mL). Organic fractions were combined, dried over sodium sulfate, filtered and evaporated. The residue was subjected to column chromatography on silica gel with eluent hexane/ethyl acetate gradient mixture, providing 2-(2-(methylthio)phenyl)pyridin-3-amine as yellow crystals (9.5 g). NMR confirmed the structure.

Reference： [1]Patent: US2009/134784,2009,A1

19
[ 657408-07-6 ]
[ 6298-19-7 ]
[ 89694-48-4 ]
[ 3375-31-3 ]
[ 1158807-03-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In water; acetonitrile;	Step 1. The 500 mL round-bottom flask, equipped with magnetic stirrer and reflux condenser was charged with 5-chloro-2-methoxyphenylboronic acid (9.78 g, 52 mmol), 3-amino-2-chloropyridine (7.00 g, 55 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (S-Phos, 0.43 g, 2 mol %), palladium (II) acetate (112 mg, 1 mol %), potassium carbonate (21.7 g, 157 mmol), 180 mL of acetonitrile and 20 ml of water. The flask was filled with nitrogen and heated to reflux under nitrogen atmosphere for 24 hours. Then the reaction was cooled down to room temperature, diluted with 500 mL of water and extracted with ethyl acetate (5*40 mL). Organic fractions were combined, dried over sodium sulfate, filtered and evaporated. The residue was subjected to column chromatography on silica gel with eluent hexane/ethyl acetate gradient mixture, providing 2-(5-chloro-2-methoxyphenyl)pyridin-3-amine as white crystals (9.5 g, NMR confirmed the structure).

Reference： [1]Patent: US2009/134784,2009,A1

20
[ 657408-07-6 ]
(N,N,N',N'-tetramethylethylenediamine)dimethylpalladium(II) [ No CAS ]
[ 2627-95-4 ]
[ 1222557-50-7 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 6463 - 6473

21
[ 657408-07-6 ]
di(rhodium)tetracarbonyl dichloride [ No CAS ]
Rh(CO)(P(C₆H₁₁)2C₆H₄C₆H₃(OCH₃)2)2Cl [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 6463 - 6473
[2]Dalton Transactions,2015,vol. 44,p. 19642 - 19650

22
[ 657408-07-6 ]
potassium phosphate [ No CAS ]
[ 946147-19-9 ]
[ 98-80-6 ]
[ 946147-20-2 ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0); In toluene;	Step 2 To a 500 mL round flask was added 3-(2,6-dichlorophenyl)-6,7-dimethylimidazo[1,2-f]phenanthridine (2.4 g, 6.1 mmol), phenylboronic acid (3.74 g, 30 mmol), Pd2(dba)3 (1.1 g, 1.2 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (S-Phos, 1.97 g, 4.8 mmol), potassium phosphate tribasic (7.64 g, 36 mmol), and 100 mL of toluene. The reaction was heated to reflux and stirred under a nitrogen atmosphere for 12 hours. After cooling, the mixture was purified by a silica gel column. Yield of 3-(2,6-diphenylphenyl)-6,7-dimethylimidazo[1,2-f]phenanthridine was 0.9 g.

Reference： [1]Patent: EP2243785,2010,A1

23
[ 657408-07-6 ]
potassium phosphate [ No CAS ]
3-bromo-6,7-dimethylmidazo[1,2-f]phenanthridine [ No CAS ]
[ 73852-17-2 ]
[ 946147-19-9 ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0); In toluene;	Step 1 To a 500 mL round flask was added 3-bromo-6,7-dimethylmidazo[1,2-f]phenanthridine (8.2 g, 25.2 mmol), 2,6-dichlorophenylboronic acid (19.2 g, 100.9 mmol), Pd2(dba)3 (2.29 g, 2.5 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (S-Phos, 4.11 g, 10.0 mmol), potassium phosphate tribasic (26.7 g, 126 mmol), and 250 mL of toluene. The reaction was heated to reflux and stirred under a nitrogen atmosphere for 48 hours. After cooling, the mixture was purified by a silica gel column. Yield of 3-(2,6-dichlorophenyl)-6,7-dimethylimidazo[1,2-f]phenanthridine was 2.4 g.

Reference： [1]Patent: EP2243785,2010,A1

24
[ 657408-07-6 ]
[ 946147-45-1 ]
[ 946147-46-2 ]

Yield	Reaction Conditions	Operation in experiment
62%	palladium diacetate; In toluene;	Step 3: Synthesis of 3-(2,6-diphenylphenyl)-imidazo[1,2-f]phenanthridine A 200 ml round bottom flask was charged with 3-(2,6-dichlorophenyl)-imidazo[1,2-f]phenanthridine (2.1 g, 5.8 mmol), phenyl bomic acid (2.828 g, 23.4 mmol), Pd(OAc)2 (1.127 g, 5.02 mmol), 2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl(4.11 g, 10.03 mmol), K3PO4 and 70 ml of anhydrous toluene. The reaction mixture was heated to 100 C under nitrogen for 22 hrs. The reaction mixture was concentrated to dryness and subjected to column chromatography to obtain the title compound (1.62 g, 62% yield).

Reference： [1]Patent: EP2243785,2010,A1

25
[ 657408-07-6 ]
[ 52409-22-0 ]
potassium phosphate monohydrate [ No CAS ]
[ 84110-40-7 ]
[ 1272455-58-9 ]
[ 1272455-72-7 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane; water; ethyl acetate; toluene;	Example 5 Synthesis of Compound 5 Synthesis of N-(3,5-diisobutylbiphenyl-4-yl)benzamide. A mixture of N-(3,5-dibromobiphenyl-4-yl)benzamide (8.52 g, 19.8 mmol), isobutyl boronic acid (8.06 g, 79.2 mmol), potassium phosphate monohydrate (13.7 g, 59.4 mmol), water. (50 mL) and toluene (150 mL) was purged with nitrogen for 20 min before addition of tris(dibenzylideneacetone) dipalladium(0) (0.27 g 3% Pd) and 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (0.49 g, 6 mol %). The reaction was stirred at reflux for 18 h. After cooling to ambient temperature the mixture was diluted with ethyl acetate and water. The layers were separated and the organic layer was concentrated and chromatographed on a silica gel column. Elution first with dichloromethane then dichloromethane and ethyl acetate (49:1) gave 6.53 g (86% yield) of the desired product as a solid. 1H NMR confirmed the structure. Synthesis of 1-(3,5-diisobutylbiphenyl-4-yl)-2-phenyl-1H-imidazole.

Reference： [1]Patent: US2011/57559,2011,A1

26
[ 657408-07-6 ]
potassium phosphate [ No CAS ]
[ 1083312-76-8 ]
[ 98-80-6 ]
[ 1083312-77-9 ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0); In toluene;	2,6-Bis(methoxymethoxy)biphenyl (16): Anhydrous toluene (2.0 mL) was added to a flask charged with Pd2(dba)3 (56.3 mg, 0.062 mmol), dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine (50.5 mg, 0.12 mmol), phenylboronic acid (281 mg, 2.31 mmol), and potassium phosphate (979 mg, 4.61 mmol) at room temperature. After 15 minutes, a solution of 15 (500 mg, 1.54 mmol) in anhydrous toluene (1.0 mL) was added and the resulting solution was heated to reflux for 12 hours. Upon cooling to room temperature, ether was added, the solution was filtered through SiO2 and concentrated to give 16 as a colorless amorphous solid (418 mg, 99%): 1HNMR (CDCl3, 500 MHz) 7.35-7.28 (m, 2H), 7.28-7.25 (m, 2H), 7.18-7.15 (m, 2H), 6.83 (d, J=8.3 Hz, 2H), 4.96 (s, 4H), 3.24 (s, 6H); 13C NMR (CDCl3, 125 MHz) 155.3, 155.0, 134.3, 130.8, 129.5, 128.7, 128.0, 127.6, 126.8, 122.6, 109.4 (2C), 94.9 (2C), 56.0 (2C); IR (film) numax 2955, 2928, 2901, 2359, 2341, 1587, 1466, 1439, 1400, 1244, 1153, 1099, 1080, 1041, 922, 764, 733, 700 cm-1; HRMS (ESI+) m/z: [M+Na]+ calcd for C16H18O4, 297.1103. Found, 297.1052.

Reference： [1]Patent: US2011/82098,2011,A1

27
[ 657408-07-6 ]
[ 12112-67-3 ]
[ 1268489-06-0 ]

Reference： [1]Organometallics,2011,vol. 30,p. 1668 - 1676

28
[ 694-80-4 ]
[ 151-10-0 ]
[ 16523-54-9 ]
[ 657408-07-6 ]

Yield	Reaction Conditions	Operation in experiment
36%		To a solution of 1,3-dimethoxybenzene (2 ml, 15.30 mmol) in anhydrous THF (35 ml) at 0 C., nBuLi (6.2 ml, 15.50 mmol) is added to the dropping funnel for 5 min. The reaction medium is stirred at room temperature for 3.5 h, then 2-bromochlorobenzene (1.6 ml, 13.70 mmol) is added by syringe, dropwise, at 0 C., for 30 min. After 15 min of stirring, the reaction medium is cooled to -78 C. and nBuLi (6.20 ml, 15.50 mmol) is added to the dropping funnel dropwise for 5 min. After 30 min, chlorodicyclohexylphosphine (3.03 ml, 13.70 mmol) is added. The reaction medium is maintained at -78 C. for 1 h, under rapid stirring (mechanical stirring). After returning to room temperature, the precipitate obtained is filtered on a fritted disc containing silica topped with a layer of cellulose acetate, with 600 ml ethyl acetate. The solvents are evaporated with a rotary evaporator, and the orange oil obtained is recrystallized in acetone to obtain S-Phos ligand in the form of white crystals with a yield of 36% (1.22 g, 2.97 mmol). MP: 163-165 C. (Lit. MP 162.0-162.5 C.); TLC: (AcOEt/cyclohexane 10/90). Rf=0.65; 1H-NMR (CDCl3): delta=0.99-1.26 (m, 10H, H(Cy)), 1.60-1.77 (m, 12H, H(Cy)), 3.67 (s, 6H, Me), 6.58 (d, 2H, J=8.2 Hz, H3' and H5'), 7.15-7.18 (m, 1H, H(Ar)), 7.18-7.42 (m, 3H, H(Ar)), 7.57 (d, 1H, J=7.4 Hz, H(Ar)) ppm; 13C-NMR (CDCl3): delta=26.5, 27.3, 27.4, 27.6, 29.0, 29.1, 29.8, 30.1, 33.8, 34.0 (C(Cy)), 55.3 (Cb), 103.1 (Ca), 126.2, 128.2, 128.8 (C3', C4', C5'), 130.9, 131.00, 132.4, 135.8 (C3, C4, C5, C6), 135.8, 136.1, 142.7, 143.1, 157.4 (C2', C6') ppm; IR (KBr): upsilon=3000, 2923, 2851, 1588, 1471, 1442, 1428, 1108 cm-1.

Reference： [1]Patent: US2011/184059,2011,A1 .Location in patent: Page/Page column 9

29
[ 657408-07-6 ]
potassium phosphate [ No CAS ]
[ 126726-62-3 ]
[ 133953-35-2 ]
[ 1332881-95-4 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; N2; benzaldehyde;tris-(dibenzylideneacetone)dipalladium(0); In dichloromethane; ethyl acetate; toluene;	A mixture of 2,4-dibromodibenzo[b,d]furan-3-amine (14.5 g, 42.5 mmol), benzaldehyde (4.96 g, 46.8 mmol), 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (21.44 g, 128 mmol), and potassium phosphate (45.1 g, 213 mmol) in 250 mL of toluene and 25 mL of H2O was bubbled with N2 for 20 minutes. Dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine (0.698 g, 1.701 mmol) and Pd2(dba)3 (0.389 g, 0.425 mmol) were then added, and the mixture was heated to reflux under N2 for 14 h. GC-MS indicated the reaction was done. After cooled to room temperature, the toluene layer was decanted. The aqueous layer was washed with toluene, and the organic layers were combined. 60 mL of concentrated HCl was added. The mixture was stirred at room temperature for 1 h. The precipitated was collected by filtration. The solid was dissolved in dichloromethane and neutralized with NaOH and dried over magnesium sulfate. After solvent evaporation, the residue was purified by column chromatography using 5-10% of ethyl acetate/hexanes as solvent. 6.6 g (59% yield) of product was obtained after purification. Synthesis of 2,4-diisopropyldibenzo[b,d]furan-3-amine.

Reference： [1]Patent: US2011/204333,2011,A1

30
[ 657408-07-6 ]
potassium phosphate [ No CAS ]
[ 1332882-20-8 ]
[ 126726-62-3 ]
[ 1332882-22-0 ]

Yield	Reaction Conditions	Operation in experiment
	With benzaldehyde;tris-(dibenzylideneacetone)dipalladium(0); In water; toluene;	To a degassed toluene (200 mL), 2,4-dibromodibenzo[b,d]thiophen-3-amine (12.15 g, 34.0 mmol), 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (17.15 g, 102 mmol), benzaldehyde (3.61 g, 34.0 mmol), potassium phosphate (23.51 g, 102 mmol) dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (1.676 g, 4.08 mmol) and Pd2(dba)3 (0.935 g, 1.021 mmol) and water (20 mL) were sequentially added. The solution was refluxed for overnight in an atmosphere of nitrogen and then allowed to cool to room temperature. The reaction was diluted with ethyl acetate and the organic phase was separated from the aqueous phase. The organic phase was dried over sodium sulfate and the solvent was removed under vacuum. The product was chromatographed using silica gel with ethylacetate and hexanes as the eluent. The solvent was removed to give the title compound (9.0, 95%). Synthesis of 2,4-diisopropyldibenzo[b,d]thiophen-3-amine.

Reference： [1]Patent: US2011/204333,2011,A1

31
[ 657408-07-6 ]
potassium phosphate monohydrate [ No CAS ]
[ 667937-52-2 ]
[ 126726-62-3 ]
[ 1332881-99-8 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hydroxide; benzaldehyde;tris-(dibenzylideneacetone)dipalladium(0); In water; toluene;	In a 3-neck, 500 mL round-bottom flask, 1,3-dibromodibenzo[b,d]furan-2-amine (19.24 g, 56.4 mmol), 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (30 g, 179 mmol), dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine (1.85 g, 4.51 mmol), benzaldehyde (5.7 mL, 56.4 mmol), potassium phosphate monohydrate (52 g, 226 mmol), toluene (400 mL), and water (40 mL) were mixed. Nitrogen was bubbled directly into the mixture for 15 minutes, then Pd2(dba)3 (1.03 g, 1.13 mmol) was added. The reaction mixture was heated to reflux overnight. After cooled to room temperature, the organic layer was separated. 40 mL of concentrated HCl was added to the organic layer. The mixture was vigorously stirred for 1 h. Aqueous sodium hydroxide solution was added to basify the mixture. The organic layer was separated and purify by silica gel plug eluting with 1:1 dichloromethane/hexanes 19.1 g of a brown oil was obtained. Synthesis of 1,3-diisopropyldibenzo[b,d]furan-2-amine.

Reference： [1]Patent: US2011/204333,2011,A1

32
[ 657408-07-6 ]
[ 1332882-12-8 ]

Reference： [1]Patent: US2011/204333,2011,A1

33
[ 657408-07-6 ]
[ 1332882-13-9 ]

Reference： [1]Patent: US2011/204333,2011,A1
[2]Patent: US2011/204333,2011,A1
[3]Patent: US2011/204333,2011,A1

34
[ 657408-07-6 ]
[ 1332882-14-0 ]

Reference： [1]Patent: US2011/204333,2011,A1
[2]Patent: US2011/204333,2011,A1

35
[ 657408-07-6 ]
[ 1332882-15-1 ]
[ 1332882-14-0 ]

Reference： [1]Patent: US2011/204333,2011,A1
[2]Patent: US2011/204333,2011,A1
[3]Patent: US2011/204333,2011,A1

36
[ 657408-07-6 ]
[ 1332882-15-1 ]

Reference： [1]Patent: US2011/204333,2011,A1
[2]Patent: US2011/204333,2011,A1
[3]Patent: US2011/204333,2011,A1
[4]Patent: US2011/204333,2011,A1
[5]Patent: US2011/204333,2011,A1

37
[ 657408-07-6 ]
[ 1332882-10-6 ]
[ 126726-62-3 ]
[ 1332882-12-8 ]
[ 1332882-11-7 ]

Yield	Reaction Conditions	Operation in experiment
74.1%	With nitrogen;tris-(dibenzylideneacetone)dipalladium(0); In hexane; water; ethyl acetate; toluene;	N-(1,3-dibromodibenzo[b,d]furan-4-yl)acetamide (55 g, 144 mmol), 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (72.4 g, 431 mmol) and potassium phosphate tribasic (132 g, 574 mmol) were mixed into toluene (800 mL) and water (80 mL). The mixture was bubbled with nitrogen for 20 minutes. Then Pd2(dba)3 (2.63 g, 2.87 mmol) and dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine (4.72 g, 11.49 mmol) were added into the reaction mixture. After bubbled by nitrogen for another 20 minutes, the reaction was refluxed overnight under nitrogen. After cooled to room temperature, the organic layer was washed by water, dried over sodium sulfate and concentrated. After silica gel column (30%-50% EtOAc in hexane) got N-(1,3-di(prop-1-en-2-yl)dibenzo[b,d]furan-4-yl)acetamide (32.5 g, 74.1% yield) as brown solid. Synthesis of N-(1,3-diisopropyldibenzo[b,d]furan-4-yl)acetamide.

Reference： [1]Patent: US2011/204333,2011,A1

38
[ 657408-07-6 ]
potassium phosphate [ No CAS ]
[ 1345970-20-8 ]
[ 1345143-35-2 ]
[ 98-80-6 ]
[ 1345970-19-5 ]

Yield	Reaction Conditions	Operation in experiment
79%	With N2;tris-(dibenzylideneacetone)dipalladium(0); In toluene;	A mixture of 9-(dibenzo[b,d]thiophen-4-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole (2.5 g, 5.26 mmol), 3-bromo-9-(dibenzo[b,d]thiophen-4-yl)-9H-carbazole (1.877 g, 4.38 mmol), and potassium phosphate (2.325 g, 10.96 mmol) in 100 mL of toluene and 10 mL of H2O was bubbled with N2 for 20 min. Pd2(dba)3 (0.040 g, 0.044 mmol) and dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (0.072 g, 0.175 mmol) were then added, and the mixture was heated to reflux under N2 for 24 h. 1 g of phenylboronic acid was added and refluxed for another 4 h. The mixture was cooled and toluene layer was separated. The organic extracts were dried over MgSO4, filtered and evaporated to a residue. The residue was purified by column. 2.4 g (79% yield) of product was obtained after purification.

Reference： [1]Patent: US2011/260138,2011,A1

39
[ 657408-07-6 ]
[ 97511-05-2 ]
[ 86-74-8 ]
[ 865-48-5 ]
[ 1345970-20-8 ]

Yield	Reaction Conditions	Operation in experiment
	With N2;tris-(dibenzylideneacetone)dipalladium(0); Pd2dba3; In 5,5-dimethyl-1,3-cyclohexadiene;	Example 6 Synthesis of Compound 9 Synthesis of 9-(dibenzo[b,d]thiophen-4-yl)-9H-carbazole. A mixture of 9H-carbazole (10 g, 59.8 mmol), 4-bromodibenzo[b,d]thiophene (18.89 g, 71.8 mmol), and dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (0.982 g, 2.392 mmol) in 200 mL of Xylene was bubbled with N2 for 20 min. Pd2dba3 (0.548 g, 0.598 mmol) and sodium 2-methylpropan-2-olate (8.62 g, 90 mmol) were then added, and the mixture was heated to reflux under N2 for 24 h. TLC indicated the reaction did not go to completion. 0.3 g of Pd2(dba)3 and 0.6 g of dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine was added. The reaction was continued to reflux. The reaction was monitored by GC. After another 24 h, there was still carbazole starting material remaining. Again, 0.3 g of Pd2(dba)3 and 0.6 g of dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine were added. The reaction was refluxed again for 24 h. The reaction was stopped and worked up for purification. Column was used for purification. (1:3 dichloromethane:hexanes) 10 g (47.8% yield) of product was obtained. Synthesis of 3-bromo-9-(dibenzo[b,d]thiophen-4-yl)-9H-carbazole.

Reference： [1]Patent: US2011/260138,2011,A1

40
[ 657408-07-6 ]
[ 1345970-20-8 ]
[ 73183-34-3 ]
[ 1345143-35-2 ]

Yield	Reaction Conditions	Operation in experiment
	With nitrogen; potassium acetate;Pd2dba3; In 1,4-dioxane; ethyl acetate;	3-bromo-9-(dibenzo[b,d]thiophen-4-yl)-9H-carbazole (5 g, 11.67 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (4.45 g, 17.51 mmol), potassium acetate (2.86 g, 29.2 mmol), and dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (0.192 g, 0.467 mmol) were mixed in 150 ml, of dioxane. Nitrogen was bubbled through the solution for 20 min. Pd2dba3 (0.107 g, 0.117 mmol) was added and the reaction mixture was heated up to 100 C. for 4 h. TLC indicated the reaction was done. The reaction was cooled to room temperature and filtered through Celite. After solvent evaporation, the residue was coated on Celite and purified by column using 10% ethyl acetate in hexanes as solvent. 9-(dibenzo[b,d]thiophen-4-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole (4 g, 8.41 mmol, 72.1% yield) was obtained.

Reference： [1]Patent: US2011/260138,2011,A1

41
[ 657408-07-6 ]
[ 22439-61-8 ]
[ 1060735-14-9 ]
[ 865-48-5 ]
[ 1340668-15-6 ]

Yield	Reaction Conditions	Operation in experiment
	With N2; nitrogen;tris-(dibenzylideneacetone)dipalladium(0); In 5,5-dimethyl-1,3-cyclohexadiene; hexane; dichloromethane;	Example 2 Synthesis of Compound 2 Synthesis of Compound 2. A mixture of 2-bromodibenzo[b,d]thiophene (3.22 g, 12.24 mmol), 9-phenyl-9H-9'H-3,3'-bicarbazole (2.5 g, 6.12 mmol), and sodium t-butoxide (1.764 g, 18.36 mmol) in 100 mL of xylene was bubbled with N2 for 20 min. Pd2(dba)3 (0.056 g, 0.061 mmol) and dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine (0.100 g, 0.245 mmol) were then added, and mixture was then bubbled with nitrogen for another 20 min. The reaction mixture was refluxed under N2 for 24 h. The mixture was cooled and filtered through Celite. After solvent evaporation, the residue was coated on Celite and purified by column chromatography using up to 50% dichloromethane in hexane as solvent. 9-(dibenzo[b,d]thiophen-2-yl)-9'-phenyl-9H,9'H-3,3'-bicarbazole (2.1 g, 3.55 mmol, 58.1% yield) was obtained.

Reference： [1]Patent: US2011/260138,2011,A1

42
[ 657408-07-6 ]
[ 97511-05-2 ]
[ 1060735-14-9 ]
[ 865-48-5 ]
[ 1345143-20-5 ]

Yield	Reaction Conditions	Operation in experiment
76%	With N2; nitrogen;tris-(dibenzylideneacetone)dipalladium(0); In 5,5-dimethyl-1,3-cyclohexadiene; dichloromethane;	Example 3 Synthesis of Compound 3 Synthesis of Compound 3. A mixture of 4-bromodibenzo[b,d]thiophene (2.061 g, 7.83 mmol), 9-phenyl-9H,9'H-3,3'-bicarbazole (2 g, 4.90 mmol), and sodium t-butoxide (1.412 g, 14.69 mmol) in 200 mL of xylene was bubbled with N2 for 20 min. Pd2(dba)3 (0.045 g, 0.049 mmol) and dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine (0.080 g, 0.196 mmol) were added and bubbled with nitrogen for another 20 min, then the mixture was heated to reflux under N2 for 24 h. The mixture was cooled and filtered through Celite. After solvent evaporation, the residue was coated on Celite and purified by column chromatography using 2:3 dichloromethane and hexanes as solvent. 9-(dibenzo[b,d]thiophen-4-yl)-9'-phenyl-9H,9'H-3,3'-bicarbazole (2.2 g. 3.72 mmol, 76% yield) was obtained. The product was further purified by recrystallization with dichloromethane and hexane.

Reference： [1]Patent: US2011/260138,2011,A1

43
[ 657408-07-6 ]
[ 6287-82-7 ]
[ 22751-52-6 ]
[ 98-80-6 ]
[ 201-69-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); In dichloromethane; water; ethyl acetate; toluene;	Example 4 Synthesis of Benzo[b]phenanthro[9,10-d]thiophene The synthesis is based on Tetrahedron, 37(1), 75-81, 1981. To a 500 mL 3-neck round bottom flask was added 2,3-dibromobenzo[b]thiophene (5.0 g, 17.12 mmol), phenylboronic acid (5.2 g, 42.81 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (281 mg, 0.68 mmol), K3PO4 (11.8 g, 51.36 mmol), 150 mL of toluene and 5 mL of water. N2 was bubbled directly into the flask for 20 minutes. Pd2(dba)3 (157 mg, 0.171 mmol) was added to the reaction mixture which was then heated to reflux for 5 h. Water was added to the cooled reaction mixture and the layers were separated. The aqueous layer was extracted twice with CH2Cl2 and the organic extracts were dried over MgSO4, filtered, and evaporated to yield a red oil which was dried to give 5.71 g of a red solid. The solid was purified by silica gel column chromatography (10-20% CH2Cl2 in hexanes) to yield 4.81 g of the product as a white solid. A photoreactor was loaded with 2,3-diphenylbenzo[b]thiophene (4.81 g, 16.8 mmol) and 800 mL toluene. The solution was irradiated using a medium pressure mercury lamp for 12 h. The solvent was evaporated and the residue was purified by silica gel column chromatography (0-20% of EtOAc in hexanes). The product was collected and recrystallized from hexanes (with a small amount of EtOAc to initially dissolve the material) to yield 1.61 g of product an off-white solid. Benzo[b]phenanthro[9,10-d]thiophene showed a triplet energy of 488 nm at 77 Kin 2-methylTHF.

Reference： [1]Patent: US2011/266526,2011,A1

44
[ 657408-07-6 ]
[ 239-35-0 ]
[ 1115639-92-3 ]
[ 76113-28-5 ]
[ 1345989-52-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; N2; bromine;tris-(dibenzylideneacetone)dipalladium(0); In dichloromethane; chloroform; water; toluene;	Br2 (1.53 g, 9.4 mmol) in ~50 mL CHCl3 was added dropwise to a solution of benzo[b]naphtha[2,1-d]thiophene (2.2 g, 9.4 mmol) in 300 mL of CHCl3 at room temperature. The mixture was stirring for 22 h. The reaction was quenched by aqueous Na2SO3. After workup, silica gel column chromatography (50% CH2Cl2 in hexanes) and washing with minimum amount of methanol and hexane, 2.8 g of product was obtained. Synthesis of Compound 69S. A mixture of 5-Bromobenzo[b]naphtho[2,1-d]thiophene (1.45 g, 4.6 mmol), 4,4,5,5-tetramethyl-2-(3-(triphenylen-2-yl)phenyl)-1,3,2-dioxaborolane (2.4 g, 5.58 mmol), K3PO4 (5.85 g, 27.6 mmol), 100 mL of toluene and 10 mL of water was bubbled with N2 for 15 minutes. Then Pd2(dba)3 (212 mg, 0.23 mmol) and 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (378 mg, 0.92 mmol) were added. The mixture was bubbled with N2 for another 20 minutes then brought to reflux for overnight. After workup, silica gel column chromatography (40% CH2Cl2 in hexanes), 2.2 g of product was obtained as a white solid. Compound 4S showed a triplet energy of 491 nm at 77K in 2-methylTHF.

Reference： [1]Patent: US2011/266526,2011,A1

45
[ 657408-07-6 ]
potassium phosphate [ No CAS ]
Pd₂(bda)3 [ No CAS ]
[ 1251041-55-0 ]
[ 98-80-6 ]
[ 800402-12-4 ]

Yield	Reaction Conditions	Operation in experiment
	With nitrogen; In water; toluene;	3-chlorobenzofuro[3,2-c]pyridine (2.89 g, 14 mmol), phenylboronic acid (2.56 g, 21 mmol), potassium phosphate (9.6 g, 42 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (0.45 g, 1.12 mmol) and Pd2(bda)3 (0.256 g, 0.28 mmol) were to toluene (100 mL) and water (10 mL). Nitrogen was bubbled through the solution for 30 minutes and then the solution was refluxed for overnight in an atmosphere of nitrogen. The reaction was then allowed to cool to room temperature and the organic phase was separated from the aqueous phase. The aqueous phase was washed with ethyl acetate and the organic fractions were combined and dried over sodium sulfate and the solvent removed under vacuum. The product was chromatographed using silica gel with ethyl acetate and hexanes as the eluent. The solvent was removed to give 2.77 g of title compound. Synthesis of Compound 1: Iridium intermediate (2.67 g, 3.76 mmol) and 3-phenylbenzofuro[3,2-c]pyridine (2.77 g, 11.29 mmol) was mixed in 50 mL of anhydrous ethanol.

Reference： [1]Patent: US2012/61654,2012,A1

46
[ 657408-07-6 ]
[ 956346-88-6 ]

Reference： [1]Angewandte Chemie - International Edition,2007,vol. 46,p. 7232 - 7235

47
[ 657408-07-6 ]
(2-dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl)Pd(Ph)(Cl)(NHBu₂) [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2007,vol. 46,p. 7232 - 7235
[2]Angewandte Chemie - International Edition,2007,vol. 46,p. 7232 - 7235

48
[ 1380028-15-8 ]
[ 16523-54-9 ]
[ 657408-07-6 ]

Reference： [1]European Journal of Organic Chemistry,2012,p. 2127 - 2131

49
[ 23112-96-1 ]
[ 95-50-1 ]
[ 657408-07-6 ]

Reference： [1]European Journal of Organic Chemistry,2012,p. 2127 - 2131

50
[ 657408-07-6 ]
9-methoxy-9-BBN [ No CAS ]
[ 1282582-93-7 ]
[ 79887-09-5 ]
[ 1282582-91-5 ]
[ 1282582-94-8 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium hexamethyldisilazane;tris-(dibenzylideneacetone)dipalladium(0); In tetrahydrofuran; hexane; water;	2.3) 1,4-Bis(2-(4-butylphenyl)ethynyl)-2-cyclobutylbenzene 3 7.8 g (47.0 mmol) of 1-butyl-4-ethynylbenzene are initially introduced in 100 ml of THF under nitrogen, cooled to -78 C., and 63.32 ml (63.20 mmol) of a 1M solution of lithium bis(trimethylsilyl)amide in hexane are added dropwise. After 1 hour, 63.22 ml (63.20 mmol) of a 1M solution of 9-methoxy-9-BBN in hexane are added, and the mixture is left to stir at -78 C. for 2 hours. In a second apparatus, 6.8 g (23.45 mmol) of 5, 0.916 g (1.0 mmol) of tris(dibenzylideneacetone)dipalladium(0) and 1.64 g (4.0 mmol) of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl are initially introduced in 100 ml of THF. The first solution is slowly added dropwise, and the batch is heated at 100 C. overnight. 100 ml of water are added to the cooled solution, and the mixture is extracted twice with methyl t-butyl ether (100 ml). The combined organic phases are washed with water, dried over sodium sulfate and evaporated in vacuo. The residue is purified by column chromatography and recrystallised from isopropanol, giving the title compound 3 as a solid.

Reference： [1]Patent: US2012/205583,2012,A1

51
[ 657408-07-6 ]
[ 26867-13-0 ]
[ 98-80-6 ]
[ 1399050-14-6 ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0); In water; toluene;	Synthesis of 3-nitro-N-6-diphenylpyridin-2-amine 6-chloro-3-nitro-N-phenylpyridin-2-amine (8.62 g, 34.5 mmol), phenylboronic acid (5.05 g, 41.4 mmol), dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (0.567 g, 1.381 mmol), potassium phosphate tribasic monohydrate (23.85 g, 104 mmol), 300 mL toluene and 30 mL water were added to a 3-neck 1000 mL round bottom flask. Nitrogen was bubbled directly into the mixture for 20 minutes. Pd2(dba)3 (0.316 g, 0.345 mmol) was added and the mixture refluxed overnight under nitrogen. The reaction mixture was diluted with ethyl acetate/water. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were dried over magnesium sulfate, filtered, and evaporated to a residue. The residue was purified by column chromatography eluting with 20% ethyl acetate/hexanes initially, and ethyl acetate was added to flush off the product. The product was washed with hexanes (7.58 g, 75%).

Reference： [1]Patent: US2012/228583,2012,A1

52
[ 657408-07-6 ]
[ 109-04-6 ]
potassium phosphate [ No CAS ]
[ 100124-06-9 ]
[ 1062595-43-0 ]

Yield	Reaction Conditions	Operation in experiment
18 g (62%)	tris-(dibenzylideneacetone)dipalladium(0); In hexane; dichloromethane; water; toluene;	Example 5 Synthesis of 4-(2-pyridyl)dibenzo[b,d]furan To a 1 L round-bottom flask was added 2-bromopyridine (13.80 mL, 142 mmol), dibenzo[b,d]furan-4-ylboronic acid (25 g, 118 mmol), dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (1.936 g, 4.72 mmol) and potassium phosphate tribasic monohydrate (81 g, 354 mmol) with toluene (350 mL) and water (35 mL). The reaction mixture was degassed with N2 for 20 minutes. Pd2(dba)3 (2.16 g, 2.35 mmol) was added and the reaction mixture was refluxed for 18 h. Completion of the reaction was confirmed by HPLC, GC and TLC. After cooling, the aqueous layer was removed and toluene was evaporated under reduced pressure. The residue was dissolved in dichloromethane and passed through one inch silica gel plug on a frit, eluting with dichloromethane. The crude product was chromatographed on silica gel with 20-25% ethyl acetate in hexane to give 18 g (62%) of the product. The product was confirmed by HPLC (99.6% purity) and GC/MS.

Reference： [1]Patent: US2012/292601,2012,A1

53
[ 657408-07-6 ]
potassium phosphate monohydrate [ No CAS ]
[ 823-96-1 ]
Bromo-2-(dibenzo[b,d]furan-4-yl)-4-methylpyridine [ No CAS ]
[ 1414352-88-7 ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0); In hexane; water; toluene;	Step 2 Synthesis of 2-(dibenzo[b,d]furan-4-yl)-4,5-dimethylpyridine -Bromo-2-(dibenzo[b,d]furan-4-yl)-4-methylpyridine (28.7 g, 85 mmol), dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (1.394 g, 3.39 mmol) and potassium phosphate monohydrate (58.6 g, 255 mmol) were added to toluene (500 mL) and water (50 mL) and degassed for 20 min. Trimethylboroxine (14.83 mL, 106 mmol) and Pd2(dba)3 (0.777 g, 0.849 mmol) were added and the reaction mixture heated to reflux overnight. After cooling, the organic layer was separated and the aqueous layer extracted 3*50 mL with EtOAc, dried over sodium sulfate and evaporated. The crude product was chromatographed on silica gel with 8/2 dichloromethane/EtOAc in hexane to give 19.2 g of an off-white solid which was recrystallized from hexane to give 16.8 g (83%) of the product as white needles. The product was confirmed by NMR and HPLC (99.97% pure).

Reference： [1]Patent: US2012/292601,2012,A1

54
[ 657408-07-6 ]
C₁₂H₁₀ClNPd [ No CAS ]
2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl [ No CAS ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 15 - 20

55
[ 657408-07-6 ]
[ 21264-30-2 ]
[Pd(2-dicyclohexylphosphino-2’,6’-dimethoxybiphenyl)2Cl2] [ No CAS ]

Reference： [1]Chemistry - A European Journal,2012,vol. 18,p. 15449 - 15458

56
[ 657408-07-6 ]
[ 110-91-8 ]
[ 1417184-60-1 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; acetonitrile;	Example 295 4-Fluoro-2-(2-imidazo[1,2-a]pyridin-2-yl-ethyl)-7-morpholin-4-yl-2,3-dihydro-isoindol-1-one Dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine (146 mg, 0.356 mmol), Pd2 dba3 (65.2 mg, 0.071 mmol) and K2CO3 (295 mg, 2.137 mmol) were each added sequentially rapidly to a solution of the compound from Example 280.1 (300 mg, 0.712 mmol) and morpholine (186 mg, 2.137 mmol) in DMF (3 mL). The reaction was heated in a microwave at about 140 C. for about 20 min. The mixture was purified via Gilson 281 (PHG008) (18-75% MeCN/Water (NH4OAc buffer) over 15 min.; Waters X-bridge OBD C18 19*250 mm, 10 um) to give the title compound (15 mg, 0.039 mmol, 5.54% yield). MS (ESI): m/z 381 (M+H)+, Rt: 1.77 min. 1H-NMR (400 MHz, CDCl3-d): delta 3.17 (t, J=7.2 Hz, 2H); 3.22 (s, 4H); 3.95 (t, J=4.2 Hz, 4H); 4.01 (t, J=7.2 Hz, 2H); 4.32 (s, 2H); 6.75 (t, J=6.8 Hz, 1H); 6.84 (dd, J=8.6 Hz, 1H); 7.09 (t, J=8.4 Hz, 1H); 7.16 (t, J=8 Hz, 1H); 7.43 (s, 1H); 7.54 (d, J=9.2 Hz, 1H); 8.04 (d, J=6.8 Hz, 1H).

Reference： [1]Patent: US2013/5705,2013,A1

57
[ 657408-07-6 ]
[ 1421361-83-2 ]
[ 126726-62-3 ]
[ 1421361-84-3 ]

Yield	Reaction Conditions	Operation in experiment
77%	With tris-(dibenzylideneacetone)dipalladium(0); In water; ethyl acetate; toluene;	Synthesis of 2-(dibenzo[b,d]furan-4-yl)-5-(prop-1-en-2-yl)pyridine 5-Chloro-2-(dibenzo[b,d]furan-4-yl)pyridine (9.5 g, 34.0 mmol), dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (1.1 g, 2.7 mmol), and potassium phosphate tribasic monohydrate (23.5 g, 102 mmol) were added to toluene (200 mL) and water (20 mL) and the reaction mixture was degassed with nitrogen. Pd2(dba)3 (0.622 g, 0.679 mmol) and 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (7.7 mL, 40.8 mmol) were added and the reaction mixture was heated to reflux overnight. EtOAc and water were added, the organic layer separated and the aqueous layer was extracted with 3*50 mL dichloromethane and dried over sodium sulfate. After removing the solvent under reduced pressure, 12.7 g of amber oil was obtained. The crude material was chromatographed on silica with 9/1 (v/v) hexane/EtOAc to give 7.5 g (77%) of 2-(dibenzo[b,d]furan-4-yl)-5-(prop-1-en-2-yl)pyridine as a white solid. The product was confirmed by GC/MS and used without further purification.