[ CAS No. 1009307-13-4 ] {[proInfo.proName]}

Name: 1009307-13-4|(E)-Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate|97%
Brand: Ambeed
SKU: A239843
Price: 5.0 USD
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Quality Control of [ 1009307-13-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 1009307-13-4 ]

Product Details of [ 1009307-13-4 ]

CAS No. :	1009307-13-4	MDL No. :	MFCD09027313
Formula :	C₁₁H₁₉BO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZXDDITJXZPTHFE-BQYQJAHWSA-N
M.W :	226.08	Pubchem ID :	23553751
Synonyms :

Calculated chemistry of [ 1009307-13-4 ]

Physicochemical Properties

Num. heavy atoms :	16
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.73
Num. rotatable bonds :	4
Num. H-bond acceptors :	4.0
Num. H-bond donors :	0.0
Molar Refractivity :	62.74
TPSA :	44.76 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.31 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.93
Log Po/w (WLOGP) :	1.74
Log Po/w (MLOGP) :	0.64
Log Po/w (SILICOS-IT) :	0.99
Consensus Log Po/w :	1.06

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.19
Solubility :	1.45 mg/ml ; 0.0064 mol/l
Class :	Soluble
Log S (Ali) :	-2.49
Solubility :	0.725 mg/ml ; 0.00321 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.06
Solubility :	1.98 mg/ml ; 0.00875 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.41

Safety of [ 1009307-13-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1009307-13-4 ]

* 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 [ 1009307-13-4 ]
Downstream synthetic route of [ 1009307-13-4 ]

[ 1009307-13-4 ] Synthesis Path-Upstream 1~1

1
[ 73183-34-3 ]
[ 623-47-2 ]
[ 1009307-13-4 ]

Yield	Reaction Conditions	Operation in experiment
65%	With methanol; [5-(diphenylphosphanyl)-9,9-dimethyl-9H-xanthen-4-yl]diphenylphosphane; copper(l) chloride; sodium t-butanolate In tetrahydrofuran at 20℃; for 24 h; Inert atmosphere	General procedure: CuCl (1.5 mg, 0.015 mmol), NaOt-Bu (2.9 mg, 0.03 mmol), and Xantphos ligand (8.7 mg, 0.015 mmol) were placed in an oven-dried Schlenk tube under nitrogen and THF (0.45 mL) were added. The reaction mixture was stirred for 30 min at room temperature and then bis(pinacolato)diboron (127 mg, 0.5 mmol) in THF (0.3 mL) was added. The reaction mixture was stirred for 10 min and α,β-acetylenic ester 2 (0.5 mmol) was added, followed by MeOH (40 μL, 1 mmol). The reaction tube was washed with further THF (0.2 mL), sealed, and stirred until no starting material was detected by TLC. The reaction mixture was filtered through a pad of Celite and concentrated. The product was purified by silica gel chromatography.

Reference： [1] Journal of Medicinal Chemistry, 2012, vol. 55, # 20, p. 8903 - 8925,23
[2] Organic and Biomolecular Chemistry, 2015, vol. 13, # 26, p. 7136 - 7139
[3] New Journal of Chemistry, 2018, vol. 42, # 21, p. 17346 - 17350
[4] Chemical Communications, 2008, # 6, p. 733 - 734
[5] Tetrahedron, 2012, vol. 68, # 17, p. 3444 - 3449
[6] Organic Letters, 2010, vol. 12, # 5, p. 1024 - 1027

[ 1009307-13-4 ] Synthesis Path-Downstream 1~88

1
[ 73183-34-3 ]
[ 623-47-2 ]
[ 1009307-13-4 ]

Yield	Reaction Conditions	Operation in experiment
65%	With methanol; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; copper(l) chloride; sodium t-butanolate; In tetrahydrofuran; at 20℃; for 24h;Inert atmosphere;	General procedure: CuCl (1.5 mg, 0.015 mmol), NaOt-Bu (2.9 mg, 0.03 mmol), and Xantphos ligand (8.7 mg, 0.015 mmol) were placed in an oven-dried Schlenk tube under nitrogen and THF (0.45 mL) were added. The reaction mixture was stirred for 30 min at room temperature and then bis(pinacolato)diboron (127 mg, 0.5 mmol) in THF (0.3 mL) was added. The reaction mixture was stirred for 10 min and alpha,beta-acetylenic ester 2 (0.5 mmol) was added, followed by MeOH (40 muL, 1 mmol). The reaction tube was washed with further THF (0.2 mL), sealed, and stirred until no starting material was detected by TLC. The reaction mixture was filtered through a pad of Celite and concentrated. The product was purified by silica gel chromatography.

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8903 - 8925,23
[2]Organic and Biomolecular Chemistry,2015,vol. 13,p. 7136 - 7139
[3]New Journal of Chemistry,2018,vol. 42,p. 17346 - 17350
[4]Chemical Communications,2008,p. 733 - 734
[5]Tetrahedron,2012,vol. 68,p. 3444 - 3449
[6]Organic Letters,2010,vol. 12,p. 1024 - 1027

2
[ 1009307-13-4 ]
[ 3727-31-9 ]
[ 1208167-61-6 ]

Reference： [1]Organic Letters,2010,vol. 12,p. 1024 - 1027

3
[ 1009307-13-4 ]
[ 542-92-7 ]
[ 1208167-49-0 ]

Reference： [1]Organic Letters,2010,vol. 12,p. 1024 - 1027

4
[ 1009307-13-4 ]
[ 1253201-90-9 ]
[ 1253201-43-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃; for 40h;	Example 30: 4-(2-[5-((E)-2-Ethoxycarbonyl-vinyl)-2-phenyl-thiazole-4-carboiiyl]- amino}-acetyl)-piperazine-l-carboxylic acid butyl esterTo a mixture of intermediate 27.1 (300 mg) in DME (3 mL) was added 2- ethoxycarbonylvinylboronic acid pinacol ester (133 mg) followed by [Pd(PPri3)4] (34 mg) and a solution of K2CO3 (81 mg) in H2O (1.5 mL). The flask was evacuated and backfilled with argon and the mixture was stirred at 900C for 40 h. To drive the reaction to completion the boronic ester (3x 1 eq) was added at different interval, as well as an additional portion of cat. (Ix 0.05 eq). The reaction mixture was allowed to cool to RT and was extracted with EtOAc (3x). The combined org. layers were dried over MgSO4 evaporated to dryness. Purification by CC (EtOAc/Hept 0: 1 to EtOAc/Hept 7:3) followed by preparative HPLC (I) gave 66 mg of the desired product. LC-MS: tR = 1.15 min; [M+H]+: 529.35.

Reference： [1]Patent: WO2010/122504,2010,A1 .Location in patent: Page/Page column 63

5
[ 1009307-13-4 ]
[ 1253201-50-1 ]
[ 1253201-52-3 ]
[ 1253202-00-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃;	Example 39: 4-((S)-2-[5-((E)-2-Carboxy-vinyl)-2-phenyl-thiazole-4-carbonyl]-amino}-3- hydroxy-propionyl)-piperazine-l-carboxylic acid butyl ester To a mixture of intermediate 37.2 (295 mg), ethoxycarbonylvinylboronic acid pinacol ester (148 mg) and [Pd(PPh3)4] (32 mg) was added aq. K2CO2 (2M, 0.38 mL) and DME (3 mL) and the reaction mixture stirred overnight at 900C. The mixture was evaporated to dryness and directly purified by CC (EtOAc/Hept 1 :1, then EtOAc, 1% HOAc) to give two fractions: The first eluting fraction gave after evaporation 196 mg of a yellow solid. This corresponded to the desired ethyl ester (Intermediate 39.1). A second eluting fraction was repurified by preparative TLC (CH2Cl2ZMeOH 9:1) to give 9 mg of the desired acid (Example 39). LC-MS: tR = 1.09 min; [M+H]+: 559.44 (ester). LC-MS: tR = 0.92 min; [M+H]+: 531.03 (acid).

Reference： [1]Patent: WO2010/122504,2010,A1 .Location in patent: Page/Page column 66

6
[ 1009307-13-4 ]
[ 1253201-27-2 ]
C₂₉H₃₆N₄O₈S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 1.5h;	Example 19: 4-((S)-4-Carboxy-2-{ [5-((E)-2-carboxy-vinyl)-2-phenyl-thiazole-4-carbonyl]- amino}-butyryl)-piperazine-l-carboxylic acid butyl esterTo a mixture of Example 15 (152 mg) in dioxane (1.5 mL) was added 2- ethoxycarbonylvinylboronic acid pinacol ester (64 mg) followed by [Pd(PPri3)4] (32 mg) and a solution Of K2COs (50 mg) in H2O (1.0 mL) and the reaction mixture was stirred at 900C for 1.5 h. The crude mixture was evaporated and the residue taken up in EtOH (2 mL). LiOH (50 mg) in MeOHZH2O (7:3, 1 mL) was added and the reaction mixture stirred at RT for 1 h. The reaction mixture was acidified to pH 3 with IN HCl and extracted with CH2Cl2 (3x). The combined org. phase were evaporated to dryness and purified by CC (EtOAc, then CH2Cl2MeOH 9: 1) to give 91 mg of the desired product. LC-MS: tR = 0.98 min; [M+H]+: 573.29.

Reference： [1]Patent: WO2010/122504,2010,A1 .Location in patent: Page/Page column 58

7
[ 1009307-13-4 ]
[ 740806-51-3 ]
[ 1258594-99-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; acetonitrile; at 100℃;Inert atmosphere;	Example 19Table 1Compound 19Synthesis of 3-(5-amino-2-(4-(2-(3,3-difluoro-3-phosphonopropoxy)ethoxy)-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)propanoic acid (19)Step 1: (E)-ethyl 3-(3-(tert-butoxycarbonylamino)-4-chlorophenyl)acrylate (6-3)To a solution of tert-butyl 5-bromo-2-chlorophenylcarbamate (6-1) (1.0 equiv.) in acetonitrile (0.3 M) and EtOH (0.5 M) was added K2CO3 (2.0 equiv.). The reaction was degassed and flushed with N2, then added (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (6-2) (1.2 equiv.) and Pd(PPh3)4 (0.1 equiv.). The reaction was flushed again with N2 and stirred at 100 C. overnight. After cooling to room temperature, hexane was added, and the mixture was filtered through a pad of silica, eluting with EA/Hex (1:1) until the product was completely eluted. The filtrate was concentrated and purified on Combiflash, eluting with 0-15% EA in Hex to give (E)-ethyl 3-(3-(tert-butoxycarbonylamino)-4-chlorophenyl)acrylate (6-3) as a white solid.
	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; acetonitrile; at 100℃;Inert atmosphere;	Step 1 : (E)-ethyl 3-(3-(tert-butoxycarbonylamino)-4-chlorophenyl)acrylate (3) To a solution of tert-butyl 5-bromo-2-chlorophenylcarbamate (1) (l.Oequiv.) in acetonitrile (0.3M) and EtOH (0.5M) was added K2CO3 (2.0equiv.). The reaction was degassed and flushed with N2, then added (E)-ethyl 3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)acrylate (2) (1.2equiv.) and Pd(PPh3)4 (O.lequiv.)- The reaction was flushed again with N2 and stirred at 100C overnight. After cooling to room temperature, hexane was added, and the mixture was filtered through a pad of silica, eluting with EA/Hex (1: 1) until the product was completely eluted. The filtrate was concentrated and purified on Combiflash, eluting with 0-15% EA in Hex to give (E)-ethyl 3-(3-(tert- butoxycarbonylamino)-4-chlorophenyl)acrylate (3) as a white solid.
	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; hexane; acetonitrile; at 20 - 100℃;Inert atmosphere;	To a solution of tert-butyl 5-bromo-2-chlorophenylcarbamate (6-1) (1.0 equiv.) in acetonitrile (0.3 M) and EtOH (0.5 M) was added K2CO3 (2.0 equiv.). The reaction was degassed and flushed with N2, then added (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (6-2) (1.2 equiv.) and Pd(PPh3)4 (0.1 equiv.). The reaction was flushed again with N2 and stirred at 100 C. overnight. After cooling to room temperature, hexane was added, and the mixture was filtered through a pad of silica, eluting with EA/Hex (1:1) until the product was completely eluted. The filtrate was concentrated and purified on Combiflash, eluting with 0-15% EA in Hex to give (E)-ethyl 3-(3-(tert-butoxycarbonylamino)-4-chlorophenyl)acrylate (6-3) as a white solid.

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 5868 - 5878
[2]Patent: US2011/53893,2011,A1 .Location in patent: Page/Page column 64-67
[3]Patent: WO2013/131985,2013,A1 .Location in patent: Page/Page column 20-21
[4]Patent: US9950062,2018,B2 .Location in patent: Page/Page column 124; 125; 126

8
[ 1009307-13-4 ]
[ 1258595-00-4 ]

Reference： [1]Patent: US2011/53893,2011,A1
[2]Patent: WO2013/131985,2013,A1
[3]Journal of Medicinal Chemistry,2016,vol. 59,p. 5868 - 5878
[4]Patent: US9950062,2018,B2

9
[ 1009307-13-4 ]
[ 1258595-01-5 ]

Reference： [1]Patent: US2011/53893,2011,A1
[2]Patent: WO2013/131985,2013,A1
[3]Journal of Medicinal Chemistry,2016,vol. 59,p. 5868 - 5878
[4]Patent: US9950062,2018,B2

10
[ 1009307-13-4 ]
[ 1258595-05-9 ]

Reference： [1]Patent: US2011/53893,2011,A1
[2]Patent: WO2013/131985,2013,A1
[3]Journal of Medicinal Chemistry,2016,vol. 59,p. 5868 - 5878
[4]Patent: US9950062,2018,B2

11
[ 1009307-13-4 ]
[ 1258595-06-0 ]

Reference： [1]Patent: US2011/53893,2011,A1
[2]Patent: WO2013/131985,2013,A1
[3]Journal of Medicinal Chemistry,2016,vol. 59,p. 5868 - 5878
[4]Patent: US9950062,2018,B2

12
[ 1009307-13-4 ]
ethyl 3-(5-amino-2-(4-hydroxy-2-methylphenethyl)benzo[f]-[1,7]naphthyridin-8-yl)propanoate dihydrochloride [ No CAS ]

Reference： [1]Patent: US2011/53893,2011,A1
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 5868 - 5878

13
[ 1009307-13-4 ]
[ 1299483-25-2 ]
[ 1299483-28-5 ]

Yield	Reaction Conditions	Operation in experiment
70%	With sodium carbonate;(bis(tricyclohexyl)phosphine)palladium(II) dichloride; In 1,4-dioxane; at 120℃; for 0.166667h;Inert atmosphere; Microwave irradiation;	N-Cyclopropyl-6-iodo-4-(trifluoromethyl)nicotinamide (125 mg, 0.34 mmol) and <strong>[1009307-13-4]ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate</strong> (93 mg, 0.41 mmol) were dissolved in 2 ml of 1,4-dioxane and admixed under argon with sodium carbonate (180 mg, 1.72 mmol) and bis(tricyclohexylphosphine)palladium(II) dichloride. The reaction mixture was heated in a microwave (CEM Discover) at 120 C. (80 W) for 10 min. Then the reaction mixture was filtered through kieselguhr, and the filtrate was taken up in ethyl acetate, washed with hydrochloric acid (1 M), dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue was taken up in 1.5 ml of ethanol, admixed with sodium hydroxide solution (1M) and stirred at room temperature overnight. Then the reaction mixture was added to ice-cold dilute hydrochloric acid and extracted with ethyl acetate. The organic phase was dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure.Yield: 72 mg (70% of theory).HPLC-MS: logP=1.26; mass (m/z): 301.1 (M+H)+; 1H NMR (CD3CN) 0.56-0.58 (m, 2H), 0.76-0.79 (m, 2H), 2.80-2.85 (m, 1H), 6.96 (d, 1H), 7.08 (br. s, 1H), 7.69 (d, 1H), 7.87 (s, 1H), 8.74 (s, 1H), 9.5 (br. s, 1H).

Reference： [1]Patent: US2011/105532,2011,A1 .Location in patent: Page/Page column 48

14
[ 1009307-13-4 ]
[ 1201787-20-3 ]
[ 1331786-48-1 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 120℃; for 1h;Microwave irradiation;	1 g of 3-fluoro-4-iodo-6-pyrid-3-yl-9-(toluene-4-sulfonyl)-9H-pyrrolo[2,3-b:5,4-c']dipyridine 18, 1.24 g of the boronate 20i, 212 mg of tetrakis(triphenylphosphine)palladium(0), 898 mg of caesium carbonate, 20 mL of dioxane and 5 mL of water are introduced into a microwave reactor of suitable size. The mixture is irradiated for 1 hour at 120 C. The reaction medium is poured into a mixture of ethyl acetate and water with vigorous stirring. After separation of the phases, the organic phase is dried over MgSO4, filtered and then concentrated under reduced pressure. The residue is dissolved in 10 mL of THF and 10 mL of methanol, and then 1.065 g of lithium hydroxide monohydrate dissolved in 5 mL of water are added. After stirring overnight, 100 mL of water are added and the pH is brought to 5 by addition of aqueous hydrochloric acid solution. The expected compound is recovered by filtration. 552 mg (80%) of (2E)-3-[3-fluoro-6-(pyrid-3-yl)-9H-pyrrolo[2,3-b:5,4-c']dipyrid-4-yl]prop-2-enoic acid 94 are obtained.UPLC-MS-DAD-ELSD (LS): Rt (min)=0.56; (M+H)(+): 335(+); (M-H)(-): 333(-).

Reference： [1]Patent: US2011/178053,2011,A1 .Location in patent: Page/Page column 75-76

15
[ 1009307-13-4 ]
[ 1299483-02-5 ]
[ 1299483-09-2 ]

Yield	Reaction Conditions	Operation in experiment
35%	With sodium carbonate;(bis(tricyclohexyl)phosphine)palladium(II) dichloride; In 1,4-dioxane; water; at 150℃; for 0.166667h;Inert atmosphere; Microwave irradiation;	In a 30 ml microwave vessel, 1.18 g (1 eq, 3.84 mmol) of 4-bromo-N-cyclopropyl-2-(trifluoromethyl)benzamide and 868 mg (1 eq, 3.84 mmol) of <strong>[1009307-13-4]ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate</strong> were dissolved in 8 ml of 1,4-dioxane. To this were added 9 ml of Na2CO3 (2M in water) and 283 mg (0.1 eq, 0.38 mmol) of bis(tricyclohexylphosphine)-palladium(II) dichloride, and the reaction mixture was saturated with argon for 5 min. Then the reaction mixture was heated in the microwave (CEM Discover) at 150 C. (80 watts) for 10 min. Subsequently, the dioxane solution was decanted off, the residue was washed with 1,4-dioxane and the combined organic phases were concentrated under reduced pressure. The residue was dissolved in water and washed with a small amount of diethyl ether. Subsequently, the mixture was acidified to pH=3 with 1 M HCl, and the aqueous solution was extracted with ethyl acetate (EA). After drying the organic phase and concentrating, 412 mg (35%) of (2E,Z)-3-[4-(cyclopropylcarbamoyl)-3-(trifluoromethyl)phenyl]acrylic acid were obtained as a white solid.HPLC-MS: logP=1.34, mass (m/z): 300.03 (M+H)+.1H NMR (400 MHz, d3-CD3CN): delta=7.90 (s, 1H), 7.80 (d, 1H), 7.70 (d, 1H, J=16 Hz), 7.50 (d, 1H), 6.60 (s, 1H, br), 6.55 (d, 1H, J=16 Hz), 2.80 (m, 1H), 0.75 (m, 2H), 0.55 (m, 2H).

Reference： [1]Patent: US2011/105532,2011,A1 .Location in patent: Page/Page column 41

16
[ 1009307-13-4 ]
[ 1373947-37-5 ]
[ 1360105-43-6 ]

Yield	Reaction Conditions	Operation in experiment
30%	With potassium carbonate;dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); In tetrahydrofuran; water; for 7h;Reflux; Inert atmosphere;	Example 19 Preparation of 1-(4-chlorobenzyl)-6-(3-chloro-4-isopropoxyphenylamino)-4-hydroxycarbonylethyl-1,3,5-triazine-2(1H)-one [Show Image] [Show Image] A mixture of 4-chloro-1-(4-chlorobenzyl)-6-(3-fluoro-4-isopropoxyphenylamino)-1,3,5-triazine-2(1H)-one (0.15 g, 0.34 mmol), 1,1'-bis(di-t-butylphosphinoferrocene)palladium(II) dichloride (22.23 mg, 034 mmol), and THF (3 mL) was placed in a flask under nitrogen. To the mixture were added (E)-ethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)acrylate (063 g, 0.49 mmol) and 2mol/L potassium carbonate (0.682 mL, 1.364 mmol), and the resulting mixture was heated at reflux for 7 hours. Then, the mixture was poured into water (30 mL) and the resulting mixture was extracted with chloroform (30 mL). The extract was dried over anhydrous sodium sulphate and concentrated in vacuo. The resulting residue was purified on a hight performance liquid chromatography (0.3% HCO2H H2O/MeCN 50-80%) to give 1-(4-chlorobenzyl)-6-(3-chloro-4-isopropoxyphenylamino)-ethoxycarbonylethenyl-1,3,5-triazine-2(1H)-one (05 g, yield: 30%) as pale orange oil. 1H-NMR (delta ppm TMS / DMSO-d6): 1.20-1.28 (9H, m), 4.17-4.22 (2H, m), 4.54 (1H, brs), 5.10 (2H, brs), 7.40 (8H, brs), 8.14 (1H, s), 9.77 (1H, s).

Reference： [1]Patent: EP2399910,2011,A1 .Location in patent: Page/Page column 88-89

17
(E)-diethyl (3-(2-methoxyphenyl)but-2-en-1-yl) phosphate [ No CAS ]
[ 1009307-13-4 ]
[ 1393373-82-4 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 6613 - 6617

18
[ 1009307-13-4 ]
[ 1251861-62-7 ]
[ 1393374-05-4 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 6613 - 6617

19
[ 1009307-13-4 ]
[ 1393373-87-9 ]
[ 1393373-83-5 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 6613 - 6617

20
[ 740842-73-3 ]
[ 1009307-13-4 ]
[ 1392148-66-1 ]

Yield	Reaction Conditions	Operation in experiment
57%	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 90℃; for 17h;Inert atmosphere;	To a stirred solution of te t-butyl-7-bromo-2,3- dihydrobenzo[/][1 ,4]oxazepine-4(5H)-carboxylate (480 mg, 1 .46 mmol) in dioxane (20 ml_) was added (E)-ethyl-3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl)acrylate (360 mg, 1 .61 mmol), aqueous Na2CO3 (1 .44 ml_, 2 M, 2.92 mmol) and Pd(dppf)CI2 (33 mg, 0.04 mmol). The mixture was degassed with nitrogen and then heated at 90C for 17 h. The reaction mixture was diluted with H2O and extracted into DCM. The organic layer was passed through a phase separator and concentrated. Purification by flash silica column chromatography (gradient elution /'-hex to 25% EtOAc in /-hex) gave the title compound as a yellow oil (267 mg, 57%). LCMS (ES+) 320 (M+H)+.

Reference： [1]Patent: WO2012/103008,2012,A1 .Location in patent: Page/Page column 121

21
[ 1009307-13-4 ]
[ 436799-33-6 ]
[ 1392148-24-1 ]

Yield	Reaction Conditions	Operation in experiment
45%		A stirred solution of 5-bromo-3-(trifluoromethyl)pyridine (1 .0 g, 4.42 mmol), (E)-ethyl-3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)acrylate (1 .0 g, 4.43 mmol), Pd(PPh3) (51 1 mg, 0.44 mmol) and Na2CO3 (13.3 mL, 1 M solution, 13.3 mmol) was degassed with nitrogen for 10 min and then heated to 100C for 17 h. The mixture was allowed to cool, diluted with water (20 mL), and extracted into DCM (3 x 20 mL). The product was extracted from the organic layers with sat. NaHCO3 (20 mL). The pH was adjusted to 5.5 and the resulting white precipitate collected by vacuum filtration (431 mg, 45%). LCMS indicated that the corresponding carboxylic acid had formed. In a separate flask, thionyl chloride (0.19 mL, 1 .99 mmol) was added slowly to MeOH (5 mL) at -78C, and the acid (431 mg, 1 .99 mmol) was added. The mixture was refluxed for 1 .5 h, cooled to r.t. and concentrated. The residue was dissolved in sat. NaHCO3 (20 mL) and extracted into DCM (3 x 20 mL), and the combined organic layers passed through a phase separator and concentrated to give the title compound as a colourless oil (403 mg, 88%). LCMS (ES+) 232 (M+H)+.

Reference： [1]Patent: WO2012/103008,2012,A1 .Location in patent: Page/Page column 108; 109
[2]Journal of Medicinal Chemistry,2013,vol. 56,p. 9934 - 9954

22
[ 23229-26-7 ]
[ 1009307-13-4 ]
[ 1308279-69-7 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8903 - 8925,23

23
[ 1009307-13-4 ]
rac-(trans-3,4)-4-(5-bromopyrazin-2-yl)-1-methylpyrrolidine-3-carboxylic acid (4-chlorophenyl)amide [ No CAS ]
(E)-3-{5-[4-(4-chlorophenylcarbamoyl)-1-methylpyrrolidin-3-yl]pyrazin-2-yl}acrylic acid ethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8903 - 8925,23

24
[ 1009307-13-4 ]
rac-(trans-3,4)-4-(6-chloropyridazin-3-yl)-1-methylpyrrolidine-3-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8903 - 8925,23

25
[ 141-30-0 ]
[ 1009307-13-4 ]
[ 1308279-70-0 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8903 - 8925,23

26
[ 1009307-13-4 ]
rac-(trans-3,4)-4-(6-chloropyridazin-3-yl)-1-methylpyrrolidine-3-carboxylic acid (4-chlorophenyl)amide [ No CAS ]
rac-(trans-3,4)-(E)-3-{6-[4-(4-chlorophenylcarbamoyl)-1-methylpyrrolidin-3-yl]pyridazin-3-yl}acrylic acid ethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8903 - 8925,23

27
[ 1009307-13-4 ]
[ 1445890-70-9 ]
[ 1445890-72-1 ]

Yield	Reaction Conditions	Operation in experiment
35%	With caesium carbonate; tetrakis(triphenylphosphine)palladium (0); In 1,4-dioxane; water; at 105℃; for 0.75h;Sealed tube; Microwave irradiation;	Step 2: ethyl (2E)-3-{2-chloro-5-[(dimethylamino)methyl]phenyl}acrylate A mixture of 1-(3-bromo-4-chlorophenyl)-N,N-dimethylmethanamine (0.54 g, 2.16 mmol), tetrakis(triphenylphosphine)palladium(0) (0.25 g, 0.22 mmol), cesium carbonate (2.12 g, 6.49 mmol), and <strong>[1009307-13-4]ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate</strong> (0.59 g, 2.60 mmol) in 1,4-dioxane (12 mL) and water (2.8 mL) were sealed in a vial and subjected to microwave irradiation at 105 oC for 45 min. The reaction mixture was diluted with water and EtOAc. The organic solution was separated and washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give ethyl (2E)-3-{2-chloro-5-[(dimethylamino)methyl]phenyl}acrylate (0.21 g, 35%). LCMS (FA): m/z=268.1 (M+H).

Reference： [1]Patent: US2013/165464,2013,A1 .Location in patent: Paragraph 0936

28
[ 1009307-13-4 ]
[ 1258595-07-1 ]

Reference： [1]Patent: WO2013/131985,2013,A1
[2]Patent: US9950062,2018,B2

29
[ 1009307-13-4 ]
[ 1268527-10-1 ]

Reference： [1]Patent: WO2013/131985,2013,A1

30
[ 1009307-13-4 ]
[ 1359818-36-2 ]
3-(4-chlorobenzyl)-5-(2-ethoxycarbonylethenyl)-2-(methylthio) pyrimidine-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
24%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In tetrahydrofuran;Reflux;	[Example 26] Preparation of 2-(3-chloro-4-isopropoxyphenylamino)-3-(4-chlorobenzyl)-5-(2-ethoxycarbonylethenyl) pyrimidine-4(3H)-one (I-132) To a mixture of 5-bromo-3-(4-chlorobenzyl)-2-(methylthio)pyrimidine-4(3H)-one (1.00 g, 2.89 mmol) and THF (20 mL) were added <strong>[1009307-13-4](E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl) acrylic acid ethyl ester</strong> (981 mg, 4.34 mmol), [1,1'-bis(di-t-butylphosphino)ferrocene]dichloropalladium(II) (189 mg, 0.289 mmol) and 2mol/L potassium carbonate solution (5.8 mL, 11.6 mmol), and the resulting mixture was heated at reflux for 4 hours. To the reaction mixture was added water, and the mixture was extracted with chloroform. The extract was washed by brine, dried over anhydrous sodium sulphate, and concentrated in vacuo. The resulting residue was washed by ethyl acetate to give 3-(4-chlorobenzyl)-5-(2-ethoxycarbonylethenyl)-2-(methylthio)pyrimidine-4(3H)-one (250 mg, Yield: 24%) as yellow solid. 1H-NMR (delta ppm TMS/DMSO-d6): 1.24 (3H, t, J = 6.9 Hz), 2.56 (3H, s), 4.17 (2H, q, J = 6.9 Hz), 5.27 (2H, s), 7.03 (1H, d, J = 15.9 Hz), 7.28 (2H, d, J = 8.1 Hz), 7.41 (2H, d, J = 8.1 Hz), 7.50 (1H, d, J = 15.9 Hz), 8.38 (1H, s).

Reference： [1]Patent: EP2604260,2013,A1 .Location in patent: Paragraph 0356; 0357

31
[ 1009307-13-4 ]
[ 1289109-31-4 ]
(1RS,2RS,3RS)-ethyl 2-phenyl-3-(6-(trifluoromethyl)imidazo[2,1-b]thiazol-2-yl)cyclopropanecarboxylate [ No CAS ]
(1RS,2RS,3SR)-ethyl 2-phenyl-3-(6-(trifluoromethyl)imidazo[2,1-b]thiazol-2-yl)cyclopropanecarboxylate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 9934 - 9954

32
[ 1009307-13-4 ]
[ 1289109-31-4 ]
[ 1512871-36-1 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 9934 - 9954

33
[ 1009307-13-4 ]
[ 6794-35-0 ]
ethyl (E)-3-(3-chloro-1-methyl-6-oxo-1,6-dihydropyridazin-4-yl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 90℃;Inert atmosphere;	Example 219A (E)-ethyl 3-(3-chloro-1-methyl-6-oxo-1,6-dihydropyridazin-4-yl)acrylate [0992] Example 219A was prepared according to the procedure used for the preparation of Example 9A, substituting Example 18B for Example 1A, and substituting (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate for 2-fluoro-5-nitrophenylboronic acid, respectively, to provide the title compound.

Reference： [1]Patent: US2013/331382,2013,A1 .Location in patent: Paragraph 0992

34
[ 1009307-13-4 ]
[ 162356-90-3 ]
[ 1415501-04-0 ]

Yield	Reaction Conditions	Operation in experiment
412 mg	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In toluene; at 100℃; for 120h;	Preparation Example 23 A mixture of 1 g of tert-butyl (2-bromobenzyl)carbamate, 1.12 g of <strong>[1009307-13-4]ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate</strong>, 16 mg of palladium acetate, 72 mg of dicyclohexyl(2',6'-dimethoxybiophenyl-2-yl)phosphine, 1.5 g of potassium phosphate, and 20 mL of toluene was stirred at 100 C. for 5 days. To the reaction mixture was added ether, followed by filtration through silica gel. The filtrate was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography to obtain 412 mg of ethyl (2E)-3-(2-[(tert-butoxycarbonyl)amino]methyl}phenyl)acrylate.

Reference： [1]Patent: US2014/88080,2014,A1 .Location in patent: Paragraph 0310

35
[ 1009307-13-4 ]
[ 918959-05-4 ]
ethyl (R,E)-4-(o-tolyl)hexa-2,5-dienoate [ No CAS ]
[ 1547459-67-5 ]

Reference： [1]Journal of the American Chemical Society,2014,vol. 136,p. 2149 - 2161

36
[ 1009307-13-4 ]
C₁₄H₁₈F₃O₄P [ No CAS ]
C₁₅H₁₅F₃O₂ [ No CAS ]
[ 1547459-63-1 ]

Reference： [1]Journal of the American Chemical Society,2014,vol. 136,p. 2149 - 2161

37
[ 1009307-13-4 ]
[ 1547460-40-1 ]
C₁₂H₁₈O₄ [ No CAS ]
C₁₂H₁₈O₄ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2014,vol. 136,p. 2149 - 2161

38
[ 1009307-13-4 ]
diethyl 3-phenylprop-2-enyl phosphate [ No CAS ]
ethyl (R,E)-4-phenylhexa-2,5-dienoate [ No CAS ]
[ 1547459-65-3 ]

Reference： [1]Journal of the American Chemical Society,2014,vol. 136,p. 2149 - 2161

39
[ 1009307-13-4 ]
[ 864830-51-3 ]

Reference： [1]Patent: WO2014/121416,2014,A1
[2]Patent: WO2014/123793,2014,A1

40
[ 1009307-13-4 ]
[ 1621706-06-6 ]

Reference： [1]Patent: WO2014/121416,2014,A1
[2]Patent: WO2014/123793,2014,A1

41
[ 1009307-13-4 ]
[ 1621706-07-7 ]

Reference： [1]Patent: WO2014/121416,2014,A1
[2]Patent: WO2014/123793,2014,A1

42
[ 1009307-13-4 ]
[ 1432132-82-5 ]
C₂₆H₃₀FN₃O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,2-dimethoxyethane; ethanol; water; at 80℃; for 2h;	Step 2 [0745] (E)-ethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane2-yl)acrylate (182mg,0.81mmol) was dissolved in DME (4mL) and ethanol (1.5mL). To the solution were added Compound 39 (292mg, 0.54mmol), PdCl2 (dppf) (21.9mg, 0.027mmol), and 2mol/L aqueous sodium carbonate (0.81mL, 1.61mmol), and the mixture was stirred for 2 hours at 80 C. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed by brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate = 75/25) to give Compound 40 (246mg, Yield 89%) as colorless oil. [0746] 1H-NMR (CDCl3) delta: 7.87-7.79 (3H, m), 7.67 (1H, d, J = 16.2 Hz), 7.05-6.97 (4H, m), 6.56 (1H, d, J = 16.2 Hz), 5.03-4.92 (1H, m), 4.98 (1H, td, J = 7.1, 3.0 Hz), 4.71-4.63 (1H, m), 4.32 (2H, q, J = 7.2 Hz), 4.07 (1H, dd, J = 11.3, 7.5 Hz), 3.83-3.72 (2H, m), 3.37 (1H, t, J = 9.8 Hz), 2.78-2.66 (1H, m), 1.43-1.34 (9H, m), 0.51 (3H, d, J = 6.9 Hz).

Reference： [1]Patent: EP2752410,2014,A1 .Location in patent: Paragraph 0745-0746

43
[ 1009307-13-4 ]
[ 1432132-82-5 ]
[ 1432132-87-0 ]

Reference： [1]Patent: EP2752410,2014,A1

44
[ 1009307-13-4 ]
C₃₀H₃₆BrNO₃ [ No CAS ]
C₃₅H₄₃NO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); potassium carbonate; In N,N-dimethyl acetamide; water; at 130℃; for 2h;	First Step Synthesis of Compound (104) [1174] Compound (101) (200 mg, 0.371 mmol) was dissolved in DMA (2 mL), and ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (126 mg, 0.557 mmol), [1,1?-bis(di-tert-butylphosphino)ferrocene]palladium dichloride (48.4 mg, 0.074 mmol), and a 2 mol/L aqueous potassium carbonate solution (0.371 mL, 0.743 mmol) were added, and the mixture was sealed and stirred at 130 C. for 2 hours. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel chromatography (hexane-ethyl acetate) to give compound (104) (143 mg, 69% yield). [1175] MS: m/z=580.4 [M+H]+.

Reference： [1]Patent: US2014/249306,2014,A1 .Location in patent: Paragraph 1173-1175

45
[ 1009307-13-4 ]
[ 1350915-20-6 ]
(1R,3aS,5aR,5bR,7aR,11aS,13aR,13bR)-benzyl 9-((E)-3-ethoxy-3-oxoprop-1-enyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 1.5h;Inert atmosphere;	A mixture of (1R,3aS,5aR,5bR,7aR,11aR,13aR,13bR)-benzyl 5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-9-(trifluoromethylsulfonyloxy)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylate, prepared as described in WO2011153315, (50 mg, 0.074 mmol), (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (66.8 mg, 0.295 mmol), tetrakis(triphenylphosphine)palladium (8.54 mg, 0.0074 mmol) and sodium carbonate (39 mg, 0.369 mmol) in DME (1 mL) and water (1 mL) was heated to 100 C. for 1.5 hours. The reaction mixture was cooled to rt, extracted with ethyl acetate (3*5 mL). The extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography with 80-100% ethyl acetate/hexanes gradient to provide the title compound (20 mg, 43%). LCMS: m/e 627.55 (M+H)+, 3.60 min (method 6).

Reference： [1]Patent: US2014/243298,2014,A1 .Location in patent: Paragraph 0328

46
[ 1009307-13-4 ]
2-(5-chloro-2-ethoxy-4-fluoro-3-iodophenyl)-2-methyl-1,3-dioxolane [ No CAS ]
ethyl (2E)-3-[3-chloro-6-ethoxy-2-fluoro-5-(2-methyl-1,3-dioxolan-2-yl)phenyl]acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 80℃; for 2h;Inert atmosphere;	Step 2. Ethyl (2E)-3-[3-chloro-6-ethoxy-2-fluoro-5-(2-methyl-1,3-dioxolan-2-yl)phenyl]acrylate A mixture of 2-(5-chloro-2-ethoxy-4-fluoro-3-iodophenyl)-2-methyl-1,3-dioxolane (22 g, 58 mmol) (from Step 1), <strong>[1009307-13-4]ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate</strong> (16 mL, 70 mmol), and potassium carbonate (24 g, 170 mmol) in 1,4-dioxane (230 mL) and water (110 mL) was degassed with nitrogen for 10 min. The reaction mixture was treated with [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (2.4 g, 2.9 mmol), degassed with nitrogen for another 10 min, and heated at 80 C. for 2 h. The reaction mixture was filtered through Celite and washed with ethyl acetate (300 mL). The filtrate was poured into water (400 mL). The aqueous layer was separated and extracted with additional ethyl acetate (300 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated to a crude brown solid. The crude material was purified by flash column chromatography using ethyl acetate in hexanes (0%-30%) to give the desired product (20 g, 96%). 1H NMR (400 MHz, CDCl3) delta 7.74 (d, J=16.5 Hz, 1H), 7.56 (d, J=8.6 Hz, 1H), 6.70 (dd, J=16.5, 0.9 Hz, 1H), 4.26 (q, J=7.1 Hz, 2H), 4.10-3.99 (m, 2H), 3.91 (q, J=7.0 Hz, 2H), 3.87-3.76 (m, 2H), 1.73 (s, 3H), 1.44 (t, J=7.0 Hz, 3H), 1.33 (t, J=7.1 Hz, 3H). LCMS for C17H21ClFO5 (M+H)+: m/z=359.1. Found: 359.1.
96%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; at 80℃; for 2h;Inert atmosphere;	A mixture of 2-(5-chloro-2-ethoxy-4-fluoro-3-iodophenyl)-2-methyl-1,3-dioxolane (22 g, 58 mmol) (from Step 1), <strong>[1009307-13-4]ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate</strong> (16 mL, 70 mmol), and potassium carbonate (24 g, 170 mmol) in 1,4-dioxane (230 mL) and water (110 mL) was degassed with nitrogen for 10 min. The reaction mixture was treated with [1,1?-bis (diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (2.4 g, 2.9 mmol), degassed with nitrogen for another 10 min, and heated at 80 C. for 2 h. The reaction mixture was filtered through Celite and washed with ethyl acetate (300 mL). The filtrate was poured into water (400 mL). The aqueous layer was separated and extracted with additional ethyl acetate (300 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated to a crude brown solid. The crude material was purified by flash column chromatography using ethyl acetate in hexanes (0%-30%) to give the desired product (20 g, 96%). NMR (400 MHz, CDCl3) delta 7.74 (d, J=16.5 Hz, 1H), 7.56 (d, J=8.6 Hz, 1H), 6.70 (dd, J=16.5, 0.9 Hz, 1H), 4.26 (q, J=7.1 Hz, 2H), 4.10-3.99 (m, 2H), 3.91 (q, J=7.0 Hz, 2H), 3.87-3.76 (m, 2H), 1.73 (s, 3H), 1.44 (t, J=7.0 Hz, 3H), 1.33 (t, J=7.1 Hz, 3H). LCMS for C17H21CIFO5 (M+H)+: m/z=359.1; Found: 359.1.

Reference： [1]Patent: US2014/249132,2014,A1 .Location in patent: Paragraph 0567
[2]Patent: US2019/365764,2019,A1 .Location in patent: Paragraph 0285-0286
[3]ACS Medicinal Chemistry Letters,2019,vol. 10,p. 1554 - 1560

47
[ 1009307-13-4 ]
(R)-4-[4-(2-amino-phenylcarbamoyl)-2-bromo-thiazol-5-yl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester [ No CAS ]
(R)-4-[4-(2-amino-phenylcarbamoyl)-2-((E)-2-carboxy-vinyl)-thiazol-5-yl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
702 mg	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In N,N-dimethyl-formamide; at 100℃; for 24h;Inert atmosphere;	A mixture of (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (1.81 g), Pd(PPh3)2Cl2 (551 mg), intermediate 224.1 (3.9 g) in DMF (70 mL) and 1M Na2CO3 (39.3 mL) was stirred at 100 C. under argon for 24 h. The reaction mixture was allowed to cool down, diluted with EA and washed with citric acid (10%), water and brine. The aq. layers were extracted with EA. The combined org. layers were dried over MgSO4, filtrated off and evaporated to dryness to afford 6.33 g of brown oil. CC (Biotage, SNAP 100 g cartridge, solvent A: DCM; solvent B: DCM/MeOH 8/2; gradient in % B: 5 for 4CV, 5 to 15 over 4CV, 15 for 5CV; second CC: SNAP 50 g cartridge, solvent A: DCM; solvent B: DCM/MeOH 8/2; gradient in % B: 5 for 5CV, 5 to 15 over 10CV, 15 for 5CV) afforded 702 mg of brown resin. LC-MS (B): tR=0.78 min; [M+H]+: 488.54.

Reference： [1]Patent: US2014/371204,2014,A1 .Location in patent: Paragraph 0956

48
[ 1009307-13-4 ]
N-(4-bromo-benzyl)-N-methyl-4-phenylsulfamoyl-benzamide [ No CAS ]
(E)-3-(4-[N-methyl-(4-phenylsulfamoyl-benzoyl)-amino]-methyl}-phenyl)-acrylic acid ethyl ester [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2014,vol. 6,p. 53 - 57

49
[ 1009307-13-4 ]
C₁₅H₂₀BNO₆ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 7136 - 7139

50
[ 1009307-13-4 ]
ethyl-8-methyl-2,12-dioxo-2,3,5a,8,9,9a-hexahydro-5H-4λ⁴,10λ⁴-10,4-(epoxyethano)benzo[3,4][1,2]azaborolo[2,1-b][1,3,2]oxazaborole-9-carboxylate [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 7136 - 7139

51
[ 1009307-13-4 ]
(E)-(3-ethoxy-3-oxoprop-1-en-1-yl)boronic acid [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 7136 - 7139
[2]Angewandte Chemie - International Edition,2019,vol. 58,p. 11049 - 11053
Angew. Chem.,2019,vol. 131,p. 11165 - 11169,5

52
potassium hydrogen difluoride [ No CAS ]
[ 1009307-13-4 ]
ethyl (E)-3-(trifluoro-l4-boranyl)acrylate, potassium salt [ No CAS ]

53
[ 1009307-13-4 ]
2-((tert-butyldimethylsilyloxy)methyl)-5-(5,6-dichloropyridin-3-yl)-1,3,4-oxadiazole [ No CAS ]
(E)-ethyl 3-(5-(5-((tert-butyldimethylsilyloxy)methyl)-1,3,4-oxadiazol-2-yl)-3-chloropyridin-2-yl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate; In 1,4-dioxane; ethanol; at 90℃; for 6h;Inert atmosphere;	To a solution of (5) (109 mg, 0.302 mmol) in dioxane (1.0 ml) and EtOH (1.0 ml) were added (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (82 mg, 0.363 mmol), PdCl2(PPh3)4 (12.7 mg, 0.018 mmol) and K3PO4 (64.2 mg, 0.302 mmol) at room temperature under nitrogen. Then the reaction mixture was heated to 90 C. After being stirred for 6 hrs at 90 C., the reaction mixture was quenched with H2O and extracted with ethyl acetate. The resulting organic layer was washed with H2O and brine, dried over Na2SO4 and concentrated in vacuo. The liquid residue was chromatographed on silica gel eluting with a gradient of hexane/ethyl acetate (5-15%) to afford 81.9 mg of the desired product (59a) in 64% as a yellow solid. (0864) 1H-NMR (DMSO-d6) delta: 9.14 (1H, s), 8.51 (1H, s), 7.98 (1H, d, J=16.17 Hz), 7.06 (1H, d, J=15.16 Hz), 4.99 (2H, s), 4.25 (2H, q, J=7.07 Hz), 1.28 (3H, t, J=7.07 Hz), 0.89 (9H, s), 0.14 (6H, s). LC/MS (M+1): 424.

Reference： [1]Patent: US9156830,2015,B2 .Location in patent: Page/Page column 113

54
[ 1009307-13-4 ]
[ 1359818-36-2 ]
[ 1359818-38-4 ]

Yield	Reaction Conditions	Operation in experiment
24%	With dichloro[1,1?-bis[bis(1,1-dimethylethyl)phosphino]ferrocene-P,P?]palladium; potassium carbonate; In tetrahydrofuran; for 4h;Reflux;	EXAMPLE 24 Preparation of 2-(3-chloro-4-isopropoxyphenylamino)-3-(4-chlorobenzyl)-5-(2-ethoxycarbonylethenyl) pyrimidine-4(3H)-one (I-132) To a mixture of 5-bromo-3-(4-chlorobenzyl)-2-(methylthio)pyrimidine-4(3H)-one (1.00 g, 2.89 mmol) and THF (20 mL) were added <strong>[1009307-13-4](E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl) acrylic acid ethyl ester</strong> (981 mg, 4.34 mmol), [1,1'-bis(di-t-butylphosphino)ferrocene]dichloropalladium(II) (189 mg, 0.289 mmol) and 2 mol/L potassium carbonate solution (5.8 mL, 11.6 mmol), and the resulting mixture was heated at reflux for 4 hours. To the reaction mixture was added water, and the mixture was extracted with chloroform. The extract was washed by brine, dried over anhydrous sodium sulphate, and concentrated in vacuo. The resulting residue was washed by ethyl acetate to give 3-(4-chlorobenzyl)-5-(2-ethoxycarbonylethenyl)-2-(methylthio)pyrimidine-4(3H)-one (250 mg, Yield: 24%) as yellow solid. 1H-NMR (delta ppm TMS/DMSO-d6): 1.24 (3H, t, J=6.9 Hz), 2.56 (3H, s), 4.17 (2H, q, J=6.0 Hz), 5.27 (2H, s), 7.03 (1H, d, J=15.9 Hz), 7.28 (2H, d, J=8.1 Hz), 7.41 (2H, d, J=8.1 Hz), 7.50 (1H, d, J=15.9 Hz), 8.38 (1H, s).

Reference： [1]Patent: US9212130,2015,B2 .Location in patent: Page/Page column 228

55
[ 1009307-13-4 ]
5-(5-bromo-2-methoxybenzyl)-N⁴-pentyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine [ No CAS ]
(E)-ethyl 3-(3-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-4-methoxyphenyl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); In water; butan-1-ol; at 100℃;Inert atmosphere;	Step 3: Preparation of (E)-ethyl 3-(3-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-dlpyrimidin-5- yl)methyl)-4-methoxyphenyl)acrylate5-(5-Bromo-2-methoxybenzyl)-N4-pentyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine (from the previous step, 1 equiv.), <strong>[1009307-13-4](E)-ethyl 3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)acrylate</strong> (1 .5 equiv.), tris(dibenzylideneacetone)dipalladium(0) (0.1 equiv.), 2-dicyclohexylphosphino-2',6'- dimethoxybiphenyl (Sphos, 0.2 equiv.) and K3P04 (2 equiv.) were dissolved in 4:1 n- butanohwater (0.1 M). After degassing with N2, the vessel was sealed and heated at 100 C O/N. After cooling down to room temperature, the reaction mixture was quenched with equal volume of saturated sodium bicarbonate aqueous solution, and was extracted with DCM. The organic layers were combined and dried over anhydrous sodium sulfate, and concentrated in vacuuo. The crude was purified by reverse phase prep-HPLC to afford title compound as a white solid.

Reference： [1]Patent: WO2015/168279,2015,A1 .Location in patent: Page/Page column 52; 53

56
[ 1009307-13-4 ]
5-(5-bromo-2-methoxybenzyl)-N⁴-pentyl-5H-pyrrolo[3,2-d]pyrimidine-2,4-diamine [ No CAS ]
ethyl 3-(3-((2-amino-4-(pentylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)methyl)-4-methoxyphenyl)propanoate [ No CAS ]

Reference： [1]Patent: WO2015/168279,2015,A1

57
[ 1009307-13-4 ]
1-(5-bromo-4-fluoropyridin-2-yl)-3-methylurea [ No CAS ]
(E)-ethyl 3-(4-fluoro-6-(3-methylureido)pyridin-3-yl)acrylate [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 666 - 670

58
[ 1009307-13-4 ]
1-[5-(4-bromophenoxy)-4-methyl-2,3-dihydro-1H-indol-1-yl]-2-[2-(methylsulfonyl)phenyl]ethanone [ No CAS ]
ethyl (2E)-3-{4-[(4-methyl-1-[2-(methylsulfonyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)oxy]phenyl}prop-2-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25.0 mg		The compound obtained in Example 1b (100 mg), 2-(ethoxycarbonyl)vinyl boronic acid pinacol ester (67.8 mg), 1,2-dimethoxyethane (2mL), aqueous solution of sodium carbonate (63.6 mg) (1 mL) was added, and the mixture was stirred at room temperature for 5 minutes. [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethanecomplex (16.3 mg) was added at a microwave reactor and allowed to react for 15 minutes at 130 C. The reaction mixture was cooled to room temperature and extracted with water was added ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (92.5 mg) as a white solid.

Reference： [1]Patent: JP2016/108257,2016,A .Location in patent: Paragraph 0209-0211

59
[ 1009307-13-4 ]
6-chloro-3-methyl-3H-[1,2,3]triazolo[4,5-c]pyridine [ No CAS ]
(E)-ethyl 3-(3-methyl-3H-[1,2,3]triazolo[4,5-c]pyridin-6-yl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16.66%	With tetrakis(triphenylphosphine) palladium(0); triethylamine; In N,N-dimethyl-formamide; at 140℃; for 12h;	A mixture of 6-chloro-3-methyl-3H-[1 ,2,3]triazolo[4,5-c]pyridine (3.000 g, 17.80 mmol), (E)-ethyl3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)acrylate (9.90 mL, 89 mmol), TEA (12.40 mL, 89mmol), tetrakis(triphenylphosphine)palladium(0) (1 .453 g, 1 .780 mmol) in N,Ndimethylformamide (50 mL) was stirred at 140 C for 12 h. The reaction mixture was filtered and the filtrate was purified by silica gel chromatography (hexane:ethyl acetate=4:1) to afford the title compound (E)-ethyl 3-(3-methyl-3H-[1 ,2,3]triazolo[4,5-c]pyridin-6-yl)acrylate (71 0 mg,2.97 mmcl, 16.66 % yield). LC-MS m/z 233.0 (M+H), 1 .51 mm (ret. time).
710 mg	With tetrakis(triphenylphosphine) palladium(0); triethylamine; In N,N-dimethyl-formamide; at 140℃; for 12h;	A mixture of 6-chloro-3-methyl-3H-[1,2,3]triazolo[4,5-c]pyridine (3.000 g, 17.80 mmol), (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (9.90 mL, 89 mmol), TEA (12.40 mL, 89 mmol), tetrakis(triphenylphosphine)palladium(0) (1.453 g, 1.780 mmol) in N,N- dimethylformamide (50 mL) was stirred at 140C for 12 h. The reaction mixture was filtered and the filtrate was purified by silica gel chromatography (hexane:ethyl acetate=4:1) to afford the title compound (E)-ethyl 3-(3-methyl-3H-[1,2,3]triazolo[4,5-c]pyridin-6-yl)acrylate (710 mg, 2.97 mmol, 16.66 % yield). LC-MS m/z 233.0 (M+H)+, 1.51 min (ret. time).

Reference： [1]Patent: WO2016/203401,2016,A1 .Location in patent: Page/Page column 192; 193
[2]Patent: WO2018/104766,2018,A1 .Location in patent: Page/Page column 194

60
[ 1009307-13-4 ]
6-chloro-3,7-dimethyl-3H-[1,2,3]triazolo[4,5-c]pyridine [ No CAS ]
(E)-ethyl 3-(3,7-dimethyl-3H-[1,2,3]triazolo[4,5-c]pyridin-6-yl)acrylate [ No CAS ]

Reference： [1]Patent: WO2016/202253,2016,A1 .Location in patent: Page/Page column 134

61
[ 1009307-13-4 ]
ethyl 24-amino-25-iodo-4-oxo-3-aza-1(4,2)pyridina-2(1,2)benzenacyclononaphane-9-carboxylate [ No CAS ]
ethyl (E)-24-amino-25-(3-ethoxy-3-oxoprop-1-en-1-yl)-4-oxo-3-aza-1(4,2)pyridina-2(1,2)benzenacyclononaphane-9-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In N,N-dimethyl-formamide; at 80℃; for 12h;Inert atmosphere;	To a mixture of ethyl 24-amino-25-iodo-4-oxo-3-aza- 1 (4,2)-pyridina-2( 1 ,2)-benzenacyclononaphane-9-carboxylate (60 mg, 0.125 mmol) in DMF(1.0 mL) was added K2C03 (17.30 mg, 0.125 mmol), (E)-ethyl 3-(4,4,5,5-tetramethyl-i,3,2-dioxaborolan-2-yl)acrylate (28.3 mg, 0.125 mmol), PdC12(dppf) (92 mg, 0.125 mmol). Themixture was then stirred at 80C for 12 h under N2. The reaction mixture was concentrated and the residue was purified by prep-TLC (5i02, DCM:MeOH=8: 1) to give the title compound. LC/MS (ESI) m/z 452.2(M+i).

Reference： [1]Patent: WO2017/74833,2017,A1 .Location in patent: Page/Page column 80; 81; 84

62
[ 1009307-13-4 ]
C₅₀H₆₄BrN₃O₁₀S₂ [ No CAS ]
C₅₅H₇₁N₃O₁₂S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In tetrahydrofuran; water; at 130℃; for 0.5h;Microwave irradiation;	Step 4 (0694) Ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)acrylate (125mg, 0.554mmol), PdCl2 (dppf) CH2Cl2 (22.6mg, 0.028mmol) and 2 mol/L sodium carbonate aqueous solution (0.554mL, 1.11mmol) were added into THF (5.6mL) solution of Compound 47 (271mg, 0.268mmol), and the mixture was stirred at 130C by using a microwave device for 30 minutes. After brine was added into the reaction mixture, the mixture was extracted with chloroform. After the organic layer was dried with magnesium sulfate anhydrous, the solvent was removed in vacuo. The obtained residue was purified by silica gel column chromatography (chloroform-methanol) to give Compound 48 (244mg, 88%).

Reference： [1]Patent: EP3192794,2017,A1 .Location in patent: Paragraph 0691; 0694

63
[ 1009307-13-4 ]
[ 1268527-08-7 ]

Reference： [1]Patent: US9950062,2018,B2

64
[ 1009307-13-4 ]
4,6-dichloro-5-(2-methoxybenzyl)pyrimidin-2-amine [ No CAS ]
ethyl (E)-3-(2-amino-6-chloro-5-(2-methoxybenzyl)pyrimidin-4-yl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 3h;Inert atmosphere;	To a solution of 4,6-dichloro-5-(2-methoxybenzyl)pyrimidin-2-amine (1.0 eq) in 3:1 dioxane/H2O (0.14M) was added ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (1.2 eq), K2CO3 (2.0 eq), and Pd(dppf)Cl2 (0.1 eq). The mixture was stirred at 100 C. for 3 h under nitrogen. The reaction was diluted with water, and the aqueous phase was extracted with EA. Combined organic layers were washed with water, then brine, dried over Na2SO4, and concentrated. The crude product was purified by column chromatography (PE/EA=40:3) to give the title compound as light yellow solid.

Reference： [1]Patent: US2018/155298,2018,A1 .Location in patent: Paragraph 1078; 1083

65
[ 56-05-3 ]
[ 1009307-13-4 ]
ethyl (E)-3-(2-amino-6-chloropyrimidin-4-yl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere;	To a solution of 4,6-dichloropyrimidin-2-amine (1.0 eq) in 3:1 dioxane/H2O (0.3M) was added ethyl (E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (1.1 eq), K2CO3 (2.0 eq), and Pd(dppf)Cl2 (0.1 eq). The mixture was stirred at 100 C. for 2 h under nitrogen. The reaction was diluted with water, and the aqueous layer was extracted with EA. The combined organic layers were washed with water, brine, dried over Na2SO4, and concentrated. The crude product was purified by column chromatography (PE/EA=10:1) to give the title compound as a yellow solid.

Reference： [1]Patent: US2018/155298,2018,A1 .Location in patent: Paragraph 1106; 1108

66
[ 1009307-13-4 ]
[ 239137-39-4 ]
[ 1452560-16-5 ]

Yield	Reaction Conditions	Operation in experiment
3.1 g	With palladium diacetate; potassium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In tetrahydrofuran; water; at 80℃; for 16h;	A mixture of 3-amino-4-bromopyridine (5.0 g, 28.9 mmol), (E)-ethyl 3-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl) acrylate (7.84 g, 34.7 mmol), Pd(OAc)2 (250 mg), Xantphos (400 mg) and K2CO3 (5.18 g, 37.6 mmol) in THF (150 mL) and H20 (30 mL) was stirred at 80 C for 16 hrs. The resulting mixture was filtered. The filtrate was diluted with EA (100 mL), washed with brine (100 mL), then dried over Na2S04 and concentrated in vacuo. The residue was purified by column (PE:EA=10: 1 to DCM: MeOH = 50: 1, v:v) to give ethyl (E)-3- (3-amino-4-pyridyl)prop-2-enoate (3.1 g) as a brown solid.

Reference： [1]Patent: WO2018/83136,2018,A1 .Location in patent: Page/Page column 34; 35

67
[ 13472-85-0 ]
[ 1009307-13-4 ]
[ 72716-96-2 ]