[ CAS No. 287944-10-9 ] {[proInfo.proName]}

Name: 287944-10-9|2-(Cyclopent-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane|98%
Brand: Ambeed
SKU: A106873
Price: 7.0 USD
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2D 3D

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Quality Control of [ 287944-10-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 287944-10-9 ]

SDS Specification

Alternatived Products of [ 287944-10-9 ]

Product Details of [ 287944-10-9 ]

CAS No. :	287944-10-9	MDL No. :	MFCD08669391
Formula :	C₁₁H₁₉BO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JFTZVYKESKQING-UHFFFAOYSA-N
M.W :	194.08	Pubchem ID :	15486611
Synonyms :

Calculated chemistry of [ 287944-10-9 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.82
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	59.35
TPSA :	18.46 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.74 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	2.46
Log Po/w (WLOGP) :	2.73
Log Po/w (MLOGP) :	1.67
Log Po/w (SILICOS-IT) :	1.69
Consensus Log Po/w :	1.71

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.53
Solubility :	0.577 mg/ml ; 0.00297 mol/l
Class :	Soluble
Log S (Ali) :	-2.49
Solubility :	0.626 mg/ml ; 0.00322 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.62
Solubility :	0.463 mg/ml ; 0.00239 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.64

Safety of [ 287944-10-9 ]

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

Application In Synthesis of [ 287944-10-9 ]

* 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 [ 287944-10-9 ]
Downstream synthetic route of [ 287944-10-9 ]

[ 287944-10-9 ] Synthesis Path-Upstream 1~11

1
[ 930-29-0 ]
[ 73183-34-3 ]
[ 287944-10-9 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium acetate In 1,4-dioxane at 110℃; for 3 h; Inert atmosphere	Example XIV2-Cyclopent-1 -enyl-4,4,5,5-tetramethyl-[1 ,3,21dioxaborolane Under argon 4,31 g 1 -chlor-1 -cyclopenten and 12,5 g bis-(pinacolato)-diboron are dissolved 160 ml 1 ,4-dioxane, mixed with 8 g potassium acetate and purged for 5 minutes with argon. 370 mg Tris-(dibenzylidenaceton)-dipalladium-(0) ([Pd₂dba₃] and 780 mg 2- cyclohexylphosphino-2',4',6'-triisopropyl-1 ,1 '-biphenyl are added and the mixture is heated for 3 hours to 1 10°C. After cooling to room temperature it is diluted with diethylether and washed with water and brine. The organic phase is dried with magnesium sulphate and the solvents are evaporated in vacuo. The residue is triturated with petrole ether. After removing the precipitate by filtration the solvent of the mother liquor is evaporated in vacuo.Yield: 13,1 g (99 percent of theory)Mass spectrometry (El): m/z = 194 [M]⁺
99%	With potassium acetate In 1,4-dioxane at 110℃; for 3 h; Inert atmosphere	Under argon 4.31 g 1-chlor-1-cyclopenten and 12.5 g bis-(pinacolato)-diboron are dissolved 160 ml 1,4-dioxane, mixed with 8 g potassium acetate and purged for 5 minutes with argon. 370 mg Tris-(dibenzylidenaceton)-dipalladium-(0) ([Pd₂dba₃] and 780 mg 2-cyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl are added and the mixture is heated for 3 hours to 110° C. After cooling to room temperature it is diluted with diethylether and washed with water and brine. The organic phase is dried with magnesium sulphate and the solvents are evaporated in vacuo. The residue is triturated with petrole ether. After removing the precipitate by filtration the solvent of the mother liquor is evaporated in vacuo.Yield: 13.1 g (99percent of theory)Mass spectrometry (EI): m/z=194 [M]⁺
99%	With 2-cyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl; potassium acetate In 1,4-dioxane at 110℃; for 3 h; Inert atmosphere	Example XIV 2-Cvclopent-1-enyl-4,4,5,5-tetramethyl-[1 ,3,21dioxaborolane Under argon 4,31 g 1-chlor-1-cyclopenten and 12,5 g bis-(pinacolato)-diboron are dissolved 160 ml 1 ,4-dioxane, mixed with 8 g potassium acetate and purged for 5 minutes with argon. 370 mg Tris-(dibenzylidenaceton)-dipalladium-(0) ([Pd₂dba₃] and 780 mg 2- cyclohexylphosphino-2',4',6'-triisopropyl-1 ,1 '-biphenyl are added and the mixture is heated for 3 hours to 110°C. After cooling to room temperature it is diluted with diethylether and washed with water and brine. The organic phase is dried with magnesium sulphate and the solvents are evaporated in vacuo. The residue is triturated with petrole ether. After removing the precipitate by filtration the solvent of the mother liquor is evaporated in vacuo.Yield: 13, 1 g (99 percent of theory)Mass spectrometry (El): m/z = 194 [M]⁺

99%

With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 2-cyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl; potassium acetate In 1,4-dioxane at 110℃; for 3 h; Inert atmosphere

Under argon 4.31 g 1-chlor-1-cyclopenten and 12.5 g bis-(pinacolato)-diboron are dissolved 160 ml 1,4-dioxane, mixed with 8 g potassium acetate and purged for 5 minutes with argon. 370 mg Tris-(dibenzylidenaceton)-dipalladium-(0) ([Pd₂dba₃] and 780 mg 2-cyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl are added and the mixture is heated for 3 hours to 110° C. After cooling to room temperature it is diluted with diethylether and washed with water and brine. The organic phase is dried with magnesium sulphate and the solvents are evaporated in vacuo. The residue is triturated with petrole ether. After removing the precipitate by filtration the solvent of the mother liquor is evaporated in vacuo.Yield: 13.1 g (99percent of theory)Mass spectrometry (EI): m/z=194 [M]⁺

Reference： [1] Patent: WO2011/101424, 2011, A1, . Location in patent: Page/Page column 230-231
[2] Patent: US2012/46304, 2012, A1, . Location in patent: Page/Page column 123
[3] Patent: WO2012/110599, 2012, A1, . Location in patent: Page/Page column 230-231
[4] Patent: US2013/53404, 2013, A1, . Location in patent: Paragraph 1781; 1782; 1783
[5] Journal of Organic Chemistry, 2012, vol. 77, # 7, p. 3543 - 3548
[6] Angewandte Chemie - International Edition, 2007, vol. 46, # 28, p. 5359 - 5363

2
[ 61676-62-8 ]
[ 17529-98-5 ]
[ 287944-10-9 ]

Reference： [1] Journal of the American Chemical Society, 2008, vol. 130, # 26, p. 8481 - 8490
[2] Synthetic Communications, 2008, vol. 38, # 22, p. 3984 - 3995

3
[ 28075-49-2 ]
[ 73183-34-3 ]
[ 287944-10-9 ]

Reference： [1] Journal of the American Chemical Society, 2002, vol. 124, # 27, p. 8001 - 8006
[2] Journal of the American Chemical Society, 2002, vol. 124, # 27, p. 8001 - 8006

4
[ 930-29-0 ]
[ 1195-66-0 ]
[ 287944-10-9 ]

Reference： [1] Patent: WO2012/148511, 2012, A1, . Location in patent: Page/Page column 62-63

5
[ 5419-55-6 ]
[ 17529-98-5 ]
[ 287944-10-9 ]

Yield	Reaction Conditions	Operation in experiment
0.9 g	Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In hexane at -78 - 20℃; for 2.75 h; Inert atmosphere Stage #2: at -78 - 20℃; for 4 h; Inert atmosphere	2-(Cyclopent-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane was synthesized in a similar procedure to the published Shapiro protocol.²² In a 250 mL round bottom flask equipped with a condenser, p-tolylsulfonylhydrazine (18.0 g, 96.0 mmol, 1.0equiv) was dissolved in 100percent EtOH (20 mL). Cyclopentanone (8.6 mL, 8.1 g, 96 mmol, 1.0 equiv) was added and the reaction heated to reflux at 100 °C. After 5 min the suspension dissolved, and after another 15 min, a white solid appeared. After refluxing for 1.5 h the reaction flask was cooled to 0 °C and the resulting solid was then collected by filtration and washed with ice-cold EtOH. After drying under reduced pressure, the hydrazone was isolated as a white powder in a quantitative yield. The cyclopentanone p-tolylsulfonylhydrazine (1.62 g, 5.40 mmol, 1.00 equiv) and 20 mL dry hexane was added to a flame dried 250 mL round bottom flask equipped with a septum and magnetic stirbar. To this mixture anhydrous TMEDA (20 mL) was added and the reaction cooled to –78 °C, where it was maintained for15 min, after which 2.5 M n-BuLi (10 mL, 25 mmol, 4.6 equiv) was added. The reaction mixture was then stirred at –78 °C for 1 h and then warmed to room temperature and stirred for 1.5 h at this temperature during this time N2 gas was extruded from the reaction and after the allotted time the reaction was cooled backdown to –78 °C and maintained for 15 min, after which pinacol isopropyl borate (5.5 mL, 4.5 g, 24 mmol, 4.4 equiv) was added. The reaction mixture was stirred at –78°C for 1 h, and then the dry ice bath was removed and the mixture was stirred at room temperature for 3 h, before being quenched via the addition of 10percent HCl (50 mL) and extracted with Et₂O (4 × 50 mL), (10percent HCl was used instead of saturated NH₄Cl, to increase the acidity on work–up. By increasing the acidity, this reduced the amount of an emulsion and allowed for easier work-up). The combined organic extracts were dried over anhydrous MgSO₄, filtered, and concentrated in vacuo. The crude product was purified via column chromatography (95:5 hexanes/EtOAc) to give the desired compound (0.90 g, 86percent) as a faint yellow oil. Spectral and analytical properties of this compound were in accordance with the literature.²²

Reference： [1] Tetrahedron, 2014, vol. 70, # 3, p. 678 - 683

6
[ 142-29-0 ]
[ 73183-34-3 ]
[ 287944-10-9 ]

Reference： [1] Journal of Organic Chemistry, 2009, vol. 74, # 20, p. 7715 - 7723
[2] Angewandte Chemie - International Edition, 2010, vol. 49, # 24, p. 4051 - 4053
[3] Angewandte Chemie - International Edition, 2010, vol. 49, # 24, p. 4051 - 4053
[4] Angewandte Chemie - International Edition, 2010, vol. 49, # 24, p. 4051 - 4053
[5] Angewandte Chemie - International Edition, 2010, vol. 49, # 24, p. 4051 - 4053

7
[ 930-29-0 ]
[ 25015-63-8 ]
[ 287944-10-9 ]

Reference： [1] Journal of Organic Chemistry, 2008, vol. 73, # 14, p. 5589 - 5591

8
[ 17497-52-8 ]
[ 25015-63-8 ]
[ 287944-10-9 ]

Reference： [1] Synthesis, 2000, # 6, p. 778 - 780

9
[ 28075-49-2 ]
[ 25015-63-8 ]
[ 287944-10-9 ]

Reference： [1] Synthesis, 2000, # 6, p. 778 - 780

10
[ 142-29-0 ]
[ 73183-34-3 ]
[ 66217-55-8 ]
[ 287944-10-9 ]

Reference： [1] Chemical Communications, 2010, vol. 46, # 6, p. 907 - 909
[2] Chemical Communications, 2010, vol. 46, # 6, p. 907 - 909

11
[ 120-92-3 ]
[ 287944-10-9 ]

Reference： [1] Tetrahedron, 2014, vol. 70, # 3, p. 678 - 683

[ 287944-10-9 ] Synthesis Path-Downstream 1~88

1
[ 930-29-0 ]
[ 73183-34-3 ]
[ 287944-10-9 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium acetate;tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; at 110℃; for 3h;Inert atmosphere;	Example XIV2-Cyclopent-1 -enyl-4,4,5,5-tetramethyl-[1 ,3,21dioxaborolane Under argon 4,31 g 1 -chlor-1 -cyclopenten and 12,5 g bis-(pinacolato)-diboron are dissolved 160 ml 1 ,4-dioxane, mixed with 8 g potassium acetate and purged for 5 minutes with argon. 370 mg Tris-(dibenzylidenaceton)-dipalladium-(0) ([Pd2dba3] and 780 mg 2- cyclohexylphosphino-2',4',6'-triisopropyl-1 ,1 '-biphenyl are added and the mixture is heated for 3 hours to 1 10C. After cooling to room temperature it is diluted with diethylether and washed with water and brine. The organic phase is dried with magnesium sulphate and the solvents are evaporated in vacuo. The residue is triturated with petrole ether. After removing the precipitate by filtration the solvent of the mother liquor is evaporated in vacuo.Yield: 13,1 g (99 % of theory)Mass spectrometry (El): m/z = 194 [M]+
99%	With potassium acetate;tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; at 110℃; for 3h;Inert atmosphere;	Under argon 4.31 g 1-chlor-1-cyclopenten and 12.5 g bis-(pinacolato)-diboron are dissolved 160 ml 1,4-dioxane, mixed with 8 g potassium acetate and purged for 5 minutes with argon. 370 mg Tris-(dibenzylidenaceton)-dipalladium-(0) ([Pd2 dba3] and 780 mg 2-cyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl are added and the mixture is heated for 3 hours to 110 C. After cooling to room temperature it is diluted with diethylether and washed with water and brine. The organic phase is dried with magnesium sulphate and the solvents are evaporated in vacuo. The residue is triturated with petrole ether. After removing the precipitate by filtration the solvent of the mother liquor is evaporated in vacuo.Yield: 13.1 g (99% of theory)Mass spectrometry (EI): m/z=194 [M]+
99%	With 2-cyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl; potassium acetate;tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; at 110℃; for 3h;Inert atmosphere;	Example XIV 2-Cvclopent-1-enyl-4,4,5,5-tetramethyl-[1 ,3,21dioxaborolane Under argon 4,31 g 1-chlor-1-cyclopenten and 12,5 g bis-(pinacolato)-diboron are dissolved 160 ml 1 ,4-dioxane, mixed with 8 g potassium acetate and purged for 5 minutes with argon. 370 mg Tris-(dibenzylidenaceton)-dipalladium-(0) ([Pd2dba3] and 780 mg 2- cyclohexylphosphino-2',4',6'-triisopropyl-1 ,1 '-biphenyl are added and the mixture is heated for 3 hours to 110C. After cooling to room temperature it is diluted with diethylether and washed with water and brine. The organic phase is dried with magnesium sulphate and the solvents are evaporated in vacuo. The residue is triturated with petrole ether. After removing the precipitate by filtration the solvent of the mother liquor is evaporated in vacuo.Yield: 13, 1 g (99 % of theory)Mass spectrometry (El): m/z = 194 [M]+

99%

With tris-(dibenzylideneacetone)dipalladium(0); 2-cyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl; potassium acetate; In 1,4-dioxane; at 110℃; for 3h;Inert atmosphere;

Under argon 4.31 g 1-chlor-1-cyclopenten and 12.5 g bis-(pinacolato)-diboron are dissolved 160 ml 1,4-dioxane, mixed with 8 g potassium acetate and purged for 5 minutes with argon. 370 mg Tris-(dibenzylidenaceton)-dipalladium-(0) ([Pd2dba3] and 780 mg 2-cyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl are added and the mixture is heated for 3 hours to 110 C. After cooling to room temperature it is diluted with diethylether and washed with water and brine. The organic phase is dried with magnesium sulphate and the solvents are evaporated in vacuo. The residue is triturated with petrole ether. After removing the precipitate by filtration the solvent of the mother liquor is evaporated in vacuo.Yield: 13.1 g (99% of theory)Mass spectrometry (EI): m/z=194 [M]+

Reference： [1]Patent: WO2011/101424,2011,A1 .Location in patent: Page/Page column 230-231
[2]Patent: US2012/46304,2012,A1 .Location in patent: Page/Page column 123
[3]Patent: WO2012/110599,2012,A1 .Location in patent: Page/Page column 230-231
[4]Patent: US2013/53404,2013,A1 .Location in patent: Paragraph 1781; 1782; 1783
[5]Journal of Organic Chemistry,2012,vol. 77,p. 3543 - 3548
[6]Angewandte Chemie - International Edition,2007,vol. 46,p. 5359 - 5363

2
[ 5044-38-2 ]
[ 287944-10-9 ]
1-(4-(cyclopenten-1-yl)phenyl)-1H-pyroole [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2007,vol. 46,p. 5359 - 5363

3
[ 845616-08-2 ]
[ 287944-10-9 ]
[ 847547-03-9 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE H 2-Cyclopent-1-enyl-5-methanesulfonyl-benzoic acid Following procedure A, 2-Cyclopent-1-enyl-5-methanesulfonyl-benzoic acid is prepared from 2-iodo-5-methanesulfonyl-benzoic acid and <strong>[287944-10-9]2-cyclopent-1-enyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane</strong> [M. Murata, T. Oyama, S. Watanabe, Y. Masuda, Synthesis 2000, 778]: MS (ISN): 264.8 M-H-.

Reference： [1]Patent: US2005/59668,2005,A1 .Location in patent: Page/Page column 16

4
[ 930-29-0 ]
[ 25015-63-8 ]
[ 287944-10-9 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 5589 - 5591

5
[ 61676-62-8 ]
[ 17529-98-5 ]
[ 287944-10-9 ]

Reference： [1]Journal of the American Chemical Society,2008,vol. 130,p. 8481 - 8490
[2]Synthetic Communications,2008,vol. 38,p. 3984 - 3995

6
[ 181658-26-4 ]
[ 287944-10-9 ]
[ 1041002-84-9 ]

Reference： [1]Journal of the American Chemical Society,2008,vol. 130,p. 8481 - 8490

7
[ 1087160-39-1 ]
[ 287944-10-9 ]
C₂₀H₂₀F₅N₃O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5643 - 5647

8
[ 142-29-0 ]
[ 73183-34-3 ]
[ 287944-10-9 ]

Reference： [1]Journal of Organic Chemistry,2009,vol. 74,p. 7715 - 7723
[2]Angewandte Chemie - International Edition,2010,vol. 49,p. 4051 - 4053
[3]Angewandte Chemie - International Edition,2010,vol. 49,p. 4051 - 4053
[4]Angewandte Chemie - International Edition,2010,vol. 49,p. 4051 - 4053
[5]Angewandte Chemie - International Edition,2010,vol. 49,p. 4051 - 4053

9
[ 142-29-0 ]
[ 73183-34-3 ]
[ 66217-55-8 ]
[ 287944-10-9 ]

Reference： [1]Chemical Communications,2010,vol. 46,p. 907 - 909
[2]Chemical Communications,2010,vol. 46,p. 907 - 909

10
[ 1256469-25-6 ]
[ 287944-10-9 ]
[ 1256469-26-7 ]

Reference： [1]Journal of Organic Chemistry,2010,vol. 75,p. 7962 - 7965

11
[ 287944-10-9 ]
[ 1332488-37-5 ]

Reference： [1]Patent: WO2011/101424,2011,A1
[2]Patent: WO2012/110599,2012,A1
[3]Patent: US2013/53404,2013,A1

12
[ 287944-10-9 ]
[ 1332488-86-4 ]

Reference： [1]Patent: WO2011/101424,2011,A1
[2]Patent: US2012/46304,2012,A1
[3]Patent: US2013/53404,2013,A1

13
[ 287944-10-9 ]
[ 1332484-87-3 ]

Reference： [1]Patent: WO2011/101424,2011,A1
[2]Patent: US2012/46304,2012,A1

14
[ 1332486-56-2 ]
[ 287944-10-9 ]
[ 1332487-50-9 ]

Yield	Reaction Conditions	Operation in experiment
74%	With cesium fluoride;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; at 50℃; for 36h;Inert atmosphere;	Example XI(R)-((S)-5-(tert-butyldimethylsilyloxy)-4-cvclopentenyl-2-isopropyl-7,7-dimethyl-5,6,7,8- tetrahvdroquinolin-3-yl)(4-(trifluoromethyl)phenyl)methanolUnder argon 490 mg (R)-((S)-5-(tert-butyldimethylsilyloxy)-4-iodo-2-isopropyl-7,7-dimethyl- 5,6,7,8-tetrahydroquinolin-3-yl)(4-(trifluoromethyl)phenyl)methanol and 900 mg 2-cyclopent- 1 -enyl-4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolane are dissolved in 20 ml tetrahydrofurane. 900 mg caesium fluoride are added and the mixture is purged for 5 minutes with argon. After the addition of 50 mg of 1 ,1 '-bis-(diphenylphosphino)-ferrocene-dichloro-palladium-(ll) the mixture is heated to 50C for 36 hours. Then the mixture is diluted with diethylether, washed with saturated aqueous ammonium chloride and brine and dried with magnesium sulphate. The solvents are evaporated in vacuo and the residue is chromatographed on silica gel(cyclohexane/ethylacetate 95:5 to 60:40).Yield: 330 mg (74 % of theory)Mass spectrometry (EST): m/z = 574 [M+H]+ Rf-value: 0,37 (silica gel, petrole ether/ethylacetate 8:1 )
74%	With cesium fluoride;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; at 50℃; for 36h;Inert atmosphere;	Under argon 490 mg (R)-((S)-5-(tert-butyldimethylsilyloxy)-4-iodo-2-isopropyl-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl)(4-(trifluoromethyl)phenyl)methanol and 900 mg <strong>[287944-10-9]2-cyclopent-1-enyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane</strong> are dissolved in 20 ml tetrahydrofurane. 900 mg caesium fluoride are added and the mixture is purged for 5 minutes with argon. After the addition of 50 mg of 1,1'-bis-(diphenylphosphino)-ferrocene-dichloro-palladium-(II) the mixture is heated to 50 C. for 36 hours. Then the mixture is diluted with diethylether, washed with saturated aqueous ammonium chloride and brine and dried with magnesium sulphate. The solvents are evaporated in vacuo and the residue is chromatographed on silica gel (cyclohexane/ethylacetate 95:5 to 60:40).Yield: 330 mg (74% of theory)Mass spectrometry (ESI+): m/z=574 [M+H]+ Rf-value: 0.37 (silica gel, petrole ether/ethylacetate 8:1)
74%	With cesium fluoride;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; at 50℃; for 36h;Inert atmosphere;	Example XI(R)-((S)-5-(tert-butyldimethylsilyloxy)-4-cvclopentenyl-2-isopropyl-7,7-dimethyl-5, 6,7,8- tetrahvdroquinolin-3-yl)(4-(trifluoromethyl)phenyl)methanolUnder argon 490 mg (R)-((S)-5-(tert-butyldimethylsilyloxy)-4-iodo-2-isopropyl-7,7-dimethyl- 5,6,7,8-tetrahydroquinolin-3-yl)(4-(trifluoromethyl)phenyl)methanol and 900 mg 2-cyclopent- 1-enyl-4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolane are dissolved in 20 ml tetrahydrofurane. 900 mg caesium fluoride are added and the mixture is purged for 5 minutes with argon. After the addition of 50 mg of 1 , 1 '-bis-(diphenylphosphino)-ferrocene-dichloro-palladium-(ll) the mixture is heated to 50C for 36 hours. Then the mixture is diluted with diethylether, washed with saturated aqueous ammonium chloride and brine and dried with magnesium sulphate. The solvents are evaporated in vacuo and the residue is chromatographed on silica gel(cyclohexane/ethylacetate 95:5 to 60:40).Yield: 330 mg (74 % of theory)Mass spectrometry (ESI+): m/z = 574 [M+H]+ Rf-value: 0,37 (silica gel, petrole ether/ethylacetate 8:1)

74%

With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; cesium fluoride; In tetrahydrofuran; at 50℃; for 36h;Inert atmosphere;

Under argon 490 mg (R)-((S)-5-(tert-butyldimethylsilyloxy)-4-iodo-2-isopropyl-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl)(4-(trifluoromethyl)phenyl)methanol and 900 mg <strong>[287944-10-9]2-cyclopent-1-enyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane</strong> are dissolved in 20 ml tetrahydrofurane. 900 mg caesium fluoride are added and the mixture is purged for 5 minutes with argon. After the addition of 50 mg of 1,1?-bis-(diphenylphosphino)-ferrocene-dichloro-palladium-(II) the mixture is heated to 50 C. for 36 hours. Then the mixture is diluted with diethylether, washed with saturated aqueous ammonium chloride and brine and dried with magnesium sulphate. The solvents are evaporated in vacuo and the residue is chromatographed on silica gel (cyclohexane/ethylacetate 95:5 to 60:40).[1084]Yield: 330 mg (74% of theory)[1085]Mass spectrometry (ESI+): m/z=574 [M+H]+[1086]Rf-value: 0.37 (silica gel, petrole ether/ethylacetate 8:1)

Reference： [1]Patent: WO2011/101424,2011,A1 .Location in patent: Page/Page column 165-166
[2]Patent: US2012/46304,2012,A1 .Location in patent: Page/Page column 82
[3]Patent: WO2012/110599,2012,A1 .Location in patent: Page/Page column 165-166
[4]Patent: US2013/53404,2013,A1 .Location in patent: Paragraph 1083; 1084; 1085; 1086
[5]Journal of Medicinal Chemistry,2014,vol. 57,p. 8766 - 8776

15
[ 287944-10-9 ]
[ 1334675-46-5 ]

Reference： [1]Patent: US2011/230462,2011,A1

16
[ 287944-10-9 ]
[ 1334675-47-6 ]

Reference： [1]Patent: US2011/230462,2011,A1

17
[ 153034-86-7 ]
[ 287944-10-9 ]
[ 1334675-45-4 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃; for 3.5h;	Step 1 To a solution of 2-cyclopentenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (681 mg, 3.51 mmol) and 2-chloro-4-iodopyridine (700 mg, 2.92 mmol) in 1,4-dioxane (12 mL) was added 2.0 M aqueous Na2CO3 (4.39 mL, 8.77 mmol) and tetrakis(triphenylphosphine)palladium(0) (67.6 mg, 0.059 mmol). The reaction mixture was heated at 90 C. for 3.5 h then cooled to room temperature, diluted with water and extracted with EtOAc (2*). The combined organics were dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography (0% to 10% EtOAc/hexanes) to afford 450 mg (86%) of 2-chloro-4-cyclopent-1-enyl-pyridine as a white solid.

Reference： [1]Patent: US2011/230462,2011,A1 .Location in patent: Page/Page column 103

18
[ 287944-10-9 ]
[ 1332490-87-5 ]

Reference： [1]Patent: US2012/46304,2012,A1
[2]Patent: US2013/53404,2013,A1

19
[ 287944-10-9 ]
[ 1332490-85-3 ]
[ 1332490-86-4 ]

Reference： [1]Patent: US2012/46304,2012,A1
[2]Patent: US2013/53404,2013,A1

20
[ 1332490-03-5 ]
[ 287944-10-9 ]
[ 1332490-10-4 ]

Yield	Reaction Conditions	Operation in experiment
55%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 110℃; for 0.5h;Inert atmosphere; closed vial; microwave irradiation;	Under argon in a microwave vial 60 mg (R)-((S)-5-(tert-butyldimethylsilyloxy)-4-iodo-2-isopropyl-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl)(4-isopropylphenyl)methanol and 57 mg <strong>[287944-10-9]2-cyclopent-1-enyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane</strong> are dissolved in 2 ml 1,2-dimethoxyethane and 197 mul of a 2 M solution of sodium carbonate in water. 11 mg Tetrakis-triphenylpalladium-(0) are added, the vial is closed and the mixture is heated for 30 minutes at 110 C. Then the mixture is diluted with ethylacetate and washed with water and brine. After drying with sodium sulphate the solvents are evaporated in vacuo and the residue is chromatographed on silica gel (cyclohexane/ethylacetate 100:0 to 95:5).Yield: 30 mg (55% of theory)Mass spectrometry (ESL): m/z=548 [M+H]+ HPLC (Method 8): Retention time=2.14 min.Rf-value: 0.4 (silica gel, cyclohexane/ethylacetate 95:5)
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 110℃; for 0.5h;Microwave vial; Inert atmosphere;	Example XXIII(R)-((S)-5-(tert-butyldimethylsilyloxy)-4-cvclopentenyl-2-isopropyl-7,7-dimethyl-5, 6,7,8- tetrahvdroquinolin-3-yl)(4-isopropylphenyl)methanolUnder argon in a microwave vial 60 mg (R)-((S)-5-(tert-butyldimethylsilyloxy)-4-iodo-2- isopropyl-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl)(4-isopropylphenyl)methanol and 57 mg 2-cyclopent-1-enyl-4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolane are dissolved in 2 ml 1 ,2- dimethoxyethane and 197 muIota of a 2 M solution of sodium carbonate in water. 11 mg Tetrakis- triphenylpalladium-(O) are added, the vial is closed and the mixture is heated for 30 minutes at 1 10C. Then the mixture is diluted with ethylacetate and washed with water and brine. After drying with sodium sulphate the solvents are evaporated in vacuo and the residue is chromatographed on silica gel (cyclohexane/ethylacetate 100:0 to 95:5).Yield: 30 mg (55 % of theory)Mass spectrometry (ESI+): m/z = 548 [M+H]+ HPLC (Method 8): Retention time = 2,14 min.Rf-value: 0,4 (silica gel, cyclohexane/ethylacetate 95:5)

Reference： [1]Patent: US2012/46304,2012,A1 .Location in patent: Page/Page column 129
[2]Patent: WO2012/110599,2012,A1 .Location in patent: Page/Page column 242-243

21
[ 1373841-92-9 ]
[ 287944-10-9 ]
[ 1373840-33-5 ]

Yield	Reaction Conditions	Operation in experiment
42%	With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 100℃; for 0.333333h;Microwave irradiationMicrowave irradiationMicrowave irradiationMicrowave irradiation;	Step a: To a mixture of 5-bromo-6-[ethyl(methylsulfonyl)amino]-2-(4-fluorophenyl)-/V-methyl- 2A7-indazole-3-carboxamide (i) (20 mg, 0.043 mmol), 1 -cyclopentenylboronic acid pinacol ester (30 pL) and PdCI2(dppf).CH2CI2 (4 mg, 0.0049 mmol) in 1 ,4-dioxane (900 pl_) was added a solution of cesium carbonate (44 mg, 0.14 mmol) in water (300 pL). The reaction was heated under microwave irradiation at 100 C for 20 min. Acetone (3 mL) was added, the mixture was filtered and the filtrate concentrated to dryness. The residue was purified by flash column chromatography eluting with MeOH/DCM (0-10 %) to give Compound (73) as a white solid (8 mg, 42 %). ESI-MS m/z calculated for [M+H]+: 457.2; found: 457.1 ; H NMR (400 MHz, CDCI3) delta 7.78 (s, 1H), 7.73 (s, 1H), 7.61 -7.54 (m, 2H), 7.26-7.18 (m, 2H), 6.25 -6.19 (m, 1H), 6.06-5.96 (m, 1H), 3.93-3.47 (m, 2H), 3.06 (s, 3H), 3.02-2.98 (m, 3H), 2.95 - 2.69 (m, 2H), 2.60 - 2.51 (m, 2H), 2.08 - 1.95 (m, 2H), 1.19 (t, J = 7.2 Hz, 3H).

Reference： [1]Patent: WO2012/51659,2012,A1 .Location in patent: Page/Page column 82-83

22
[ 1373841-92-9 ]
[ 287944-10-9 ]
[ 1373840-35-7 ]

Reference： [1]Patent: WO2012/51659,2012,A1

23
[ 287944-10-9 ]
cyclopenten-1-ylboronic acid [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 7799 - 7803

24
[ 287944-10-9 ]
[ 1402704-27-1 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 7799 - 7803

25
[ 930-29-0 ]
[ 1195-66-0 ]
[ 287944-10-9 ]

Yield	Reaction Conditions	Operation in experiment
		[0133] Example 7 Synthesis of Compound 53/B-0[0134] Synthesis of 2-(Cyclopent-l-en-l-yl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane. A mixture of 1-chlorocyclopent-l-ene (10 g, 98 mmol), ethyl ether (40 mL) and lithium (0.82 g, 118 mmol) and some broken glass (a microscope slide) were stirred in a 250 mL 3-neck at room temperature overnight. The above reaction mixture was then cooled in a dry ice/acetone bath and 2-methoxy-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (23.11 g, 146 mmol) was added dropwise over about 20 minutes. The bath was removed and the reaction was stirred at room temperature overnight. The reaction mass was then poured into a solution of 12 g of NH4C1 in 200 mL water and stirred to break up the formed emulsion, then transferred into a separator funnel. The ether layer was separated and washed ether with H20 (2 x) (the rag layer was discarded) and dried with Na2S04 to give 7.3 g of 2-(cyclopent-l-en-l-yl)-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (64% crude yield). This was taken as is to the next step.

Reference： [1]Patent: WO2012/148511,2012,A1 .Location in patent: Page/Page column 62-63

26
5-chloro-2-(3,5-dimethylphenyl)quinoline [ No CAS ]
[ 287944-10-9 ]
[ 1404491-71-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate monohydrate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); In water; toluene;Reflux;	[0135] Synthesis of 5-(cyclopent-l-en-l-yl)-2-(3,5-dimethylphenyl)quinoline. 5-chloro-2- (3,5-dimethylphenyl)quinoline (3.86 g, 14.42 mmol), 2-(cyclopent-l-en-l-yl)-4,4,5,5- tetramethyl-l,3,2-dioxaborolane (7.3 g, 47.1 mmol), dicyclohexyl(2',6'-dimethoxy-[l,l'- biphenyl]-2-yl)phosphine (0.473 g, 1.153 mmol) potassium phosphate monohydrate (39.8 g, 173 mmol) and Pd2(dba)3 (0.264 g, 0.288 mmol) were mixed in 240 mL of toluene and 40 mL of water. The system was degassed with nitrogen for 20 minutes and then refluxed overnight. After cooling to room temperature, the reaction mixture was filtered through a small plug of silica gel (with some Celite on top) and eluted with dichloromethane. The product was further purified by chromatographing on silica gel and eluting with 95:5 hexanes: ethyl acetate (v/v) to give 5.9 g (137%) yield of crude product (contains some stating ester). This crude mixture was taken onto the next step.

Reference： [1]Patent: WO2012/148511,2012,A1 .Location in patent: Page/Page column 63

27
[ 1421186-97-1 ]
[ 287944-10-9 ]
[ 1421186-63-1 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 512 - 514

28
[ 1421186-99-3 ]
[ 287944-10-9 ]
[ 1421186-69-7 ]

Yield	Reaction Conditions	Operation in experiment
51%	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; at 100℃; for 24h;Inert atmosphere;	A mixture of 1-((2-bromophenyl)ethynyl)-2-methylnaphthalene (4b) (200 mg, 0.62mmol), 2-cyclopentenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (240 mg, 1.2 mmol), Cs2CO3 (606 mg, 1.9 mmol), Pd(PPh3)4 (36 mg, 0.031 mmol) in dioxane (20 mL) was heated at 100 C for 24 h under nitrogen. The reaction mixture was filtered through celite and the precipitate was washed with ether. The organic layer was evaporated under reduced pressure and the residue was purified by silica gel column chromatography with ether and hexane (1 : 100) to give the title compound (101 mg, 51%) as liquid; 1H-NMR (400MHz, CDCl3)delta8.43 (1H, d, J = 8.4 Hz), 7.80 (1H, d, J=8.0 Hz), 7.70 (2H, t, J = 8.4 Hz), 7.53 (1H, d, J = 6.8 Hz), 7.45 (1H, t, J = 6.8 Hz), 7.36 (1H, d, J = 8.0 Hz), 7.32 (2H, d, J = 6.8Hz) 7.23 (1H, d, J = 8.4 Hz), 6.57-6.56 (1H, m), 2.90-2.85 (2H, m), 2.71 (3H, S), 2.61-2.57 (2H, m), 2.08-2.01 (2H, m); 13C-NMR (100MHz, CDCl3) d 142.1, 139.8, 139.1, 133.8, 133.7, 131.7, 131.3, 128.3, 128.21, 128.18, 127.8, 126.8, 126.5, 126.2, 125.6, 121.4, 121.3, 119.9, 99.4, 99.1, 35.8, 33.9, 23.7, 21.6; IR(CHCl3) 3053, 2949, 2843 cm-1; MS (EI) m/z (%, fragment) = 308 (100, M+), 293 (51.6, M+ - CH3), 165 (27.2, M+ - C11H12); HRMS calcd for C24H20: 308.1556. found 308.1565.

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 512 - 514

29
[ 1421187-05-4 ]
[ 287944-10-9 ]
[ 1421186-80-2 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 512 - 514

30
[ 1421187-07-6 ]
[ 287944-10-9 ]
[ 1421186-71-1 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 512 - 514

31
[ 1421187-10-1 ]
[ 287944-10-9 ]
[ 1421186-75-5 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 512 - 514

32
[ 1421187-12-3 ]
[ 287944-10-9 ]
[ 1421186-65-3 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 512 - 514

33
[ 1421187-14-5 ]
[ 287944-10-9 ]
[ 1421186-67-5 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 512 - 514

34
[ 1421187-15-6 ]
[ 287944-10-9 ]
[ 1421186-82-4 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 512 - 514

35
[ 1421187-17-8 ]
[ 287944-10-9 ]
[ 1421187-20-3 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 512 - 514

36
[ 30766-11-1 ]
[ 287944-10-9 ]
[ 1415899-13-6 ]

Yield	Reaction Conditions	Operation in experiment
31%	With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; N,N-dimethyl-formamide; at 150℃;	5-Bromo-pyridine-2-carboxylic acid (CAN 30766-11-1, 3.4 g, 17 mmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride methylene chloride complex (CAN 95464-05-4, 530 mg, 0.65 mmol) and Cs2CO3 (6.3 g, 19 mmol) were added to a solution of 2-cyclopentenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (CAN 287944-10-9, 2.5 g, 13 mmol) in DMF (50 mL) and water (10 mL). The mixture was stirred at 150 C. overnight and concentrated in vacuo. Water (50 mL) was added and the mixture was extracted with ethyl acetate (3×40 mL). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated to give the title compound (1.0 g, 31%); MS (EI): m/e=190.1 [M+H]+.
31%	With caesium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 150℃;	5-Bromo-pyridine-2-carboxylic acid (CAN 30766-11-1, 3.4 g, 17 mmol), Iota,Gamma- bis(diphenylphosphino)ferrocene-palladium(II)dichloride methylene chloride complex (CAN 95464-05-4, 530 mg, 0.65 mmol) and Cs2C03 (6.3 g, 19 mmol) were added to a solution of 2-cyclopentenyl-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (CAN 287944-10-9, 2.5 g, 13 mmol) in DMF (50 mL) and water (10 mL). The mixture was stirred at 150C overnight and concentrated in vacuo. Water (50 mL) was added and the mixture was extracted with ethyl acetate (3 x 40 mL). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated to give the title compound (1.0 g, 31%); MS (EI): m/e = 190.1 [M+H]+.

Reference： [1]Patent: US2012/316147,2012,A1 .Location in patent: Page/Page column 74
[2]Patent: WO2012/168350,2012,A1 .Location in patent: Page/Page column 154

37
[ 287944-10-9 ]
[ 1273016-21-9 ]

Reference： [1]Patent: US2012/316147,2012,A1
[2]Patent: WO2012/168350,2012,A1

38
[ 287944-10-9 ]
[ 1415899-15-8 ]

Reference： [1]Patent: US2012/316147,2012,A1
[2]Patent: WO2012/168350,2012,A1

39
[ 287944-10-9 ]
[ 1415899-17-0 ]

Reference： [1]Patent: US2012/316147,2012,A1
[2]Patent: WO2012/168350,2012,A1

40
[ 21190-87-4 ]
[ 287944-10-9 ]
[ 1415898-99-5 ]

Yield	Reaction Conditions	Operation in experiment
23%	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; N,N-dimethyl-formamide; at 100℃;	A mixture of 6-bromo-pyridine-2-carboxylic acid (CAN 21 190-87-4, 0.375 g, 1.86 mmol), 2-cyclopentenyl-4,4,5,5-tetramethyl-l ,3,2-dioxaborolane (CAN 287944-10-9, 0.3 g, 1.6 mmol), Pd(dppf)Cl2 (CAN 95464-05-4, 0.06 g, 0.08 mmol) and K2C03 (0.642 g, 4.7 mmol) in DMF (10 mL) and water (1 mL) was heated to 100C overnight. After filtration, the filtrate was concentrated and the residue was purified by column chromatography (silica gel, 15 g, eluting with 10% ethyl acetate in petroleum ether) to give the title compound (0.08 g, 23%) as white solid; MS (EI): m/e = 190.1 [M+H]+.
	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; N,N-dimethyl-formamide; at 100℃;	A mixture of 6-bromo-pyridine-2-carboxylic acid (CAN 21190-87-4, 0.375 g, 1.86 mmol), 2-cyclopentenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (CAN 287944-10-9, 0.3 g, 1.6 mmol), Pd(dppf)Cl2 (CAN 95464-05-4, 0.06 g, 0.08 mmol) and K2CO3 (0.642 g, 4.7 mmol) in DMF (10 mL) and water (1 mL) was heated to 100 C. overnight. After filtration, the filtrate was concentrated and the residue was purified by column chromatography (silica gel, 15 g, eluting with 10% ethyl acetate in petroleum ether) to give the title compound (0.08 g, 23%) as white solid; MS (EI): m/e=190.1 [M+H]+.

Reference： [1]Patent: WO2012/168350,2012,A1 .Location in patent: Page/Page column 145
[2]Patent: US2012/316147,2012,A1 .Location in patent: Page/Page column 68

41
[ 287944-10-9 ]
[ 1415899-16-9 ]

Reference： [1]Patent: US2012/316147,2012,A1
[2]Patent: WO2012/168350,2012,A1

42
[ 21190-87-4 ]
[ 287944-10-9 ]
[ 1415899-00-1 ]

Reference： [1]Patent: US2012/316147,2012,A1
[2]Patent: WO2012/168350,2012,A1

43
[ 1415898-37-1 ]
[ 287944-10-9 ]
[ 1415898-69-9 ]

Yield	Reaction Conditions	Operation in experiment
89%		The mixture of 5-bromo-6-(cyclopropylmethoxy)-pyridine-2-carboxylic acid (Example 9 d, 1.0 g, 4 mmol), 2-cyclopentenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (CAN 287944-10-9, 0.86 g, 4 mmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride methylene chloride complex (CAN 95464-05-4, 150 mg 0.18 mmol) and aqueous sodium carbonate solution (2N, 16 mL) was added to DMF (10 ml). The mixture was heated to 100 C. overnight; then the solution was diluted with water (15 mL), extracted with ethyl acetate (30 mL), the water layer was adjusted to pH=3.0 by hydrochloric acid (3N) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water (2×100 mL) and brine (80 mL) and evaporated to dryness. The residue was purified by column chromatography (silica gel, 8 g, eluting with 15% ethyl acetate in petroleum ether) to obtain the product (0.85 g, 89%) as a white solid; MS (LC/MS): 260.1 [M+H]+.
89%		The mixture of 5-bromo-6-(cyclopropylmethoxy)-pyridine-2-carboxylic acid (Example 9 d, 1.0 g, 4 mmol), 2-cyclopentenyl-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (CAN 287944- 10-9, 0.86 g, 4 mmol), l, -bis(diphenylphosphino)ferrocene-palladium(II)dichloride methylene chloride complex (CAN 95464-05-4, 150 mg 0.18 mmol) and aqueous sodium carbonate solution (2N, 16 mL) was added to DMF (10 ml). The mixture was heated to 100C overnight; then the solution was diluted with water (15 mL), extracted with ethyl acetate (30 mL), the water layer was adjusted to pH = 3.0 by hydrochloric acid (3N) and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with water (2 x 100 mL) and brine (80 mL) and evaporated to dryness. The residue was purified by column chromatography (silica gel, 8 g, eluting with 15% ethyl acetate in petroleum ether) to obtain the product (0.85 g, 89%) as a white solid; MS (LC/MS): 260.1 [M+H]+.

Reference： [1]Patent: US2012/316147,2012,A1 .Location in patent: Page/Page column 47
[2]Patent: WO2012/168350,2012,A1 .Location in patent: Page/Page column 105; 106
[3]Journal of Medicinal Chemistry,2015,vol. 58,p. 4266 - 4277

44
[ 1051372-09-8 ]
[ 287944-10-9 ]
[ 1426954-71-3 ]

Yield	Reaction Conditions	Operation in experiment
43.51%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In N,N-dimethyl-formamide; at 25 - 80℃; for 20.5h;Inert atmosphere;	To a stirred solution of 3-bromo-5-nitro-2-(2,2,2-trifluoro-ethoxy)-pyridine (Example la) (6 g, 19.9 mmol) in DMF (30 mL) was added 2-(l-cyclopenten-l-yl)-4,4,5,5-tetramethyl-l,3,2- dioxaborolane (CAN 287944-10-9) (4.64 g, 23.9 mmol) and K2C03 (8.2 g, 59.8 mmol) at 25C and the reaction mixture was degassed with argon over 30 min. To this was added PdCl2(dppf)2 dichloromethane complex (814 mg, 1.1 mmol) and the reaction mixture was heated to 80C for 20 h. The reaction mixture cooled to 25C, water (50 mL) was added, the mixture was extracted with ethyl acetate (4x50 mL), washed with water (200 mL), brine, dried with Na2S04 and concentrated. The crude material was purified by column chromatography (Combi-Flash, 40g, 2% dichloromethane/hexane) to get the title compound (2.5g, 43.51%) as pale white solid; NMR complies.
43.51%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In N,N-dimethyl-formamide; at 25 - 80℃; for 20.5h;Inert atmosphere;	To a stirred solution of 3-bromo-5-nitro-2-(2,2,2-trifluoro-ethoxy)-pyridine (Example 1a) (6 g, 19.9 mmol) in DMF (30 mL) was added <strong>[287944-10-9]2-(1-cyclopenten-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (CAN 287944-10-9) (4.64 g, 23.9 mmol) and K2CO3 (8.2 g, 59.8 mmol) at 25 C. and the reaction mixture was degassed with argon over 30 min. To this was added PdCl2 (dppf)2 dichloromethane complex (814 mg, 1.1 mmol) and the reaction mixture was heated to 80 C. for 20 h. The reaction mixture cooled to 25 C., water (50 mL) was added, the mixture was extracted with ethyl acetate (4×50 mL), washed with water (200 mL), brine, dried with Na2SO4 and concentrated. The crude material was purified by column chromatography (Combi-Flash, 40 g, 2% dichloromethane/hexane) to get the title compound (2.5 g, 43.51%) as pale white solid; NMR complies.

Reference： [1]Patent: WO2013/37704,2013,A1 .Location in patent: Page/Page column 21; 22
[2]Patent: US2013/65911,2013,A1 .Location in patent: Paragraph 0122; 0123

45
[ 1332490-02-4 ]
[ 287944-10-9 ]
[ 1332490-10-4 ]

Yield	Reaction Conditions	Operation in experiment
55%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 110℃; for 0.5h;Inert atmosphere;	Under argon in a microwave vial 60 mg (R)-((S)-5-(tert-butyldimethylsilyloxy)-4-iodo-2-isopropyl-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl)(4-isopropylphenyl)methanol and 57 mg <strong>[287944-10-9]2-cyclopent-1-enyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane</strong> are dissolved in 2 ml 1,2-dimethoxyethane and 197 mul of a 2 M solution of sodium carbonate in water. 11 mg Tetrakis-triphenylpalladium-(0) are added, the vial is closed and the mixture is heated for 30 minutes at 110 C. Then the mixture is diluted with ethylacetate and washed with water and brine.After drying with sodium sulphate the solvents are evaporated in vacuo and the residue is chromatographed on silica gel (cyclohexane/ethylacetate 100:0 to 95:5).Yield: 30 mg (55% of theory)Mass spectrometry (ESI+): m/z=548 [M+H]+ HPLC (Method 8): Retention time=2.14 min.Rf-value: 0.4 (silica gel, cyclohexane/ethylacetate 95:5)

Reference： [1]Patent: US2013/53404,2013,A1 .Location in patent: Paragraph 1879-1884

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[ 6307-87-5 ]
[ 287944-10-9 ]
[ 1445790-44-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 16h;Inert atmosphere;	Example 51 -butoxy-4-((3-cvclopentyl-5-(hvdroxymethyl)phenyl)amino)-7-(2,4-dimethoxypy yl)quinoline-3-carboxamide a) methyl 3-cvclopent-1 -en-1 -yl-5-nitrobenzoate. A mixture of 2-cyclopent-1 -en-1 -yl- 4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (20 g, 103.8 mmol), methyl 3-bromo-5- nitrobenzoate (18 g, 69.2 mmol), tetrakis(triphenylphosphine)palladium(0) (4 g, 3.46 mmol) and potassium carbonate (14 g, 103.8 mmol) in N,N- dimethylformamide (300 ml.) was stirred under nitrogen at 80 C for 16 h. The mixture was cooled to room temperature, poured into water (600 ml.) and extracted with ethyl acetate (600 ml. x 2). The extracts were concentrated in vacuo and the residue purified by chromatography on slica gel (14% ethyl acetate/petroleum ether) to afford the title compound (14.5 g, 85%) as a yellow oil. 1H NMR (300 MHz, CDCI3) ppm 2.05-2.14 (m, 2 H), 2.58-2.64 (m, 2 H), 2.75- 2.81 (m, 2 H), 3.99 (s, 3 H), 6.46-6.47 (m, 1 H), 8.38 (d, J=1.5 Hz, 1 H), 8.40 (d, J=1.5 Hz, 1 H), 8.67 (d, J=1.5 Hz, 1 H).
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; at 100℃; for 16h;	a) methyl 3-(cvclopent-1-en-1 -yl)-5-nitrobenzoate. Methyl 3-bromo-5-nitrobenzoate (5.9 g, 22.69 mmol), 2-(cyclopent-1 -en-1 -yl)-4,4,5,5-tetramethyl-1 ,3,2- dioxaborolane (5 g, 25.8 mmol), cesium carbonate (22.3 g, 68.4 mmol), [1 , 1 '- bis(diphenylphosphino)ferrocene]dichloropalladium(ll) dichloromethane adduct (0.573 g, 0.702 mmol) were dissolved in 1 ,4-dioxane (100 ml_). The mixture was heated to 100 C for 16 h, then cooled and filtered. The filtrate was partitioned between brine and ethyl acetate. The combined organics were dried (Na2S04), filtered, and concentrated. The residue was purified (silica gel, 10-60% ethyl acetate /hexane) to afford the title compound (4.45 g, 93% pure, 74%). LCMS (ES+) m/e 248 [M+H]+.

Reference： [1]Patent: WO2013/96151,2013,A1 .Location in patent: Page/Page column 122
[2]Patent: WO2013/96153,2013,A1 .Location in patent: Page/Page column 85

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[ 287944-10-9 ]
[ 1445789-14-9 ]