Name: 1201905-61-4|(E)-2-(2-Ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane|96%
Brand: Ambeed
SKU: A204130
Price: 9.0 USD
Availability: InStock
Rating: 91 (22 reviews)

1
[ 1201905-61-4 ]
3,5-dibromo-2-(trifluoromethyl)pyridine [ No CAS ]
[ 1228963-01-6 ]

Yield	Reaction Conditions	Operation in experiment
38%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 60℃;	Step 3: 3-Bromo-5-[(i^-2-ethoxyvinyl]-2-(trifluorornethyl)pyridine; To a solution of 3,5-dibromo-2-(trifluoromethyl)pyridine (1.1 1 g, 3.65 mmol) in water (9 mL) were added 2-[(£)-2-ethoxyvinyl]-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (0.72 g, 3.65 mmol), tetrakis(triphenylphosphine)-palladium(0) (0.42 g, 0.36 mmol), 1 ,2-dimethoxyethane (16.7 mL), and sodium carbonate (1.16 g, 1 1.0 mmol). The resulting mixture was allowed to stir overnight at 60 0C.After the reaction was allowed to cool to rt, EtOAc (50 mL) was added. The organic solution was separated, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give 3-bromo-5-[(£)-2-ethoxyvinyl]-2-(trifluoromethyl)pyridine (0.41 g, 38%).

Reference： [1]Patent: WO2010/65134,2010,A1 .Location in patent: Page/Page column 108

2
[ 1201905-61-4 ]
[ 1355336-53-6 ]
[ 1355336-54-7 ]

Yield	Reaction Conditions	Operation in experiment
71%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In water; acetonitrile; at 85℃; for 3h;Inert atmosphere; Microwave irradiation;	In an MW vial were successively added SPhos (30 mg, 7 mol %), Pd(OAc)2 (8 mg, 3.5 mol %), K3PO4 (450 mg, 2.12 mmol, 2 equiv), 4-chloropyridine 9 (300 mg, 1.06 mmol, 1 equiv), boronic ester 7 (399 mg, 2.02 mmol, 1.9 equiv), CH3CN (3 mL) and water (2 mL). The MW vial was purged with N2 for 5 min then heated at 85 C for 3 h under MW conditions. The resulting mixture was filtered through a pad of Celite and the pad was washed several times with EtOAc. The filtrate was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by column chromatography using EtOAc as eluent to provide (E)-tert-butyl 2-[4-(2-ethoxyvinyl)pyridin-3-yl]pyrrolidine-1-carboxylate 10 (240 mg, 71%) as an orange oil; the product was identified as a mixture of 2 rotamers in a 1.2:1 ratio; Rf=0.40 (EtOAc); 1H NMR (300 MHz): delta 8.17-8.34 (m, 2H), 7.11 (d, J=5.3, 1H), 6.99 (d, J=12.4, 1H), 5.89 (d, J=12.4, 1H), 5.14 (br d, J=7.4, 0.45H), 4.89-5.00 (m, 0.55H), 3.86-4.02 (m, 2H), 3.43-3.72 (m, 2H), 2.12-2.37 (m, 1H), 1.67-1.98 (m, 3H), 1.45 (s, 4H), 1.29-1.40 (3H), 1.18 (s, 5H); 13C NMR (75 MHz): delta 154.4, 154.3, 151.64, 151.59, 148.1, 147.9, 147.4, 146.5, 141.6, 141.3, 135.6, 134.4, 119.0, 118.8, 101.0, 80.0, 79.8, 66.7, 66.4, 57.3, 56.9, 47.6, 47.4, 34.6, 33.2, 28.9 (3C), 28.5 (3C), 23.5, 15.2; signal corresponding to the minor rotamer; HRMS (EI): MH+ found 319.2036. C18H26N2O3 requires 319.2022.

Reference： [1]Tetrahedron,2012,vol. 68,p. 1417 - 1421

3
[ 1201905-61-4 ]
C₁₄H₁₉ClN₂O₃ [ No CAS ]
[ 1355336-56-9 ]

Yield	Reaction Conditions	Operation in experiment
265 mg	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In water; acetonitrile; at 85℃; for 2h;Inert atmosphere; Microwave irradiation;	To a solution of diisopropylamine (168 muL, 1.20 mmol, 1.2 equiv) in dry THF (2 mL) under N2 at -78 C was added n-BuLi (2.5 M in hexanes, 480 muL, 1.20 mmol, 1.2 equiv). The resulting pale yellow mixture was stirred at this temperature for 10 min then warmed up to 0 C and stirred at this temperature for 10 min. After cooling back to -78 C, a solution of 3-chloropyridine 12 (113 mg, 1.00 mmol, 1 equiv) in dry THF (2 mL) was added dropwise and the reaction was stirred at -78 C for 1 h. After addition of a solution of pyrrolidinone 6 (241 mg, 1.30 mmol, 1.3 equiv) in dry THF (3 mL) over 2 min, the resulting reaction mixture was stirred at -78 C for 2 h then allowed to slowly warm up to room temperature and stirred at this temperature for 30 min. The resulting solution was quenched with water and extracted with CH2Cl2 (4×20 mL) then the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was dissolved in CH3CN (3 mL) and added into an MW vial containing SPhos (25 mg, 6 mol %), Pd(OAc)2 (7 mg, 3 mol %), K3PO4 (425 mg, 2.00 mmol, 2 equiv), boronic ester 7 (376 mg, 1.90 mmol, 1.9 equiv) and water (2 mL). The MW vial was purged with N2 for 5 min then heated at 85 C for 2 h under MW conditions. The resulting mixture was filtered through a pad of Celite and the pad was washed several times with EtOAc. The filtrate was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by column chromatography using Et2O/PE (20:1) as eluent to yield (E)-tert-butyl 4-[3-(2-ethoxyvinyl)pyridin-4-yl]-4-oxobutylcarbamate 13 (265 mg, 79%) as a yellow oil; Rf=0.35 (Et2O/PE, 20:1); 1H NMR (300 MHz): delta 8.63 (s, 1H), 8.43 (d, J=5.0, 1H), 7.28 (d, J=5.0, 1H), 6.90 (d, J=12.9, 1H), 6.12 (d, J=12.9, 1H), 4.71 (br s, 1H), 3.92 (q, J=7.2, 2H), 3.10-3.24 (m, 2H), 2.88 (t, J=7.2, 2H), 1.87 (quint, J=7.2, 2H), 1.41 (s, 9H), 1.34 (t, J=7.2, 3H); 13C NMR (75 MHz): delta 203.8, 156.2, 151.0, 148.3, 147.1, 142.4, 129.8, 121.0, 100.5, 79.6, 66.1, 40.2, 39.5, 28.7 (3C), 24.7, 15.1; HRMS (EI): MH+ found 335.1964. C18H26N2O4 requires 335.1971.

Reference： [1]Tetrahedron,2012,vol. 68,p. 1417 - 1421

4
[ 1201905-61-4 ]
[ 1355336-52-5 ]
[ 1355336-55-8 ]

Yield	Reaction Conditions	Operation in experiment
362 mg	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In water; acetonitrile; at 85℃; for 1.16667h;Inert atmosphere; Microwave irradiation;	To a solution of diisopropylamine (701 muL, 5.00 mmol, 2.5 equiv) in dry THF (5 mL) under N2 at -78 C was added n-BuLi (1.3 M in hexanes, 3.8 mL, 5.00 mmol, 2.5 equiv). The resulting pale yellow solution was stirred at this temperature for 10 min then warmed up to 0 C, stirred at this temperature for 10 min then cooled back to -78 C and transferred via cannula to a suspension of 4-chloropyridine hydrochloride 5 (300 mg, 2.00 mmol, 1 equiv) in dry THF (3 mL) over 5 min. The orange reaction mixture was stirred at -78 C for 1 h prior to the addition of a solution of pyrrolidinone 6 (481 mg, 2.60 mmol, 1.3 equiv) in dry THF (4 mL) over 5 min. The resulting reaction mixture was stirred at -78 C for 2 h then allowed to slowly warm up to room temperature overnight. The resulting solution was quenched with water and extracted with EtOAc (2×60 mL) then the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was dissolved in CH3CN (6 mL) and added into an MW vial containing SPhos (49 mg, 6 mol %), Pd(OAc)2 (14 mg, 3 mol %), K3PO4 (849 mg, 4.00 mmol, 2 equiv), boronic ester 13 (753 mg, 3.80 mmol, 1.9 equiv) and water (4 mL). The MW vial was purged with N2 for 5 min then heated at 85 C for 70 min under MW conditions. The resulting mixture was filtered through a pad of Celite and the pad was washed several times with EtOAc. The filtrate was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by column chromatography using a gradient elution (Et2O/EtOAc, 10:1 to 10:3) to yield (E)-tert-butyl 4-[4-(2-ethoxyvinyl)pyridin-3-yl]-4-oxobutylcarbamate 11 (362 mg, 54%) as a yellow oil, which solidified; the product was identified as a mixture of 2 rotamers in a 1.5:1 ratio; mp 90-93 C; Rf=0.25 (Et2O/EtOAc, 10:1); 1H NMR (300 MHz): delta 8.79 (s, 0.6H), 8.73 (s, 0.4H), 8.51 (d, J=5.5, 0.4H), 8.45 (d, J=5.5, 0.6H), 8.02 (d, J=5.5, 0.4H), 7.30 (d, J=5.5, 0.6H), 7.20 (d, J=12.9, 0.6H), 6.45-6.52 (m, 1H), 5.79 (d, J=7.2, 0.4H), 4.62 (br s, 1H), 4.07 (q, J=7.2, 0.8H), 3.98 (q, J=7.2, 1.2H), 3.17-3.27 (m, 2H), 2.93-3.01 (m, 2H), 1.87-2.02 (m, 2H), 1.34-1.46 (m, 12H); 13C NMR (75 MHz): delta 202.4, 156.1, 153.4, 151.3, 150.1, 144.5, 130.7, 119.3, 101.8, 79.3, 66.1, 40.1, 39.3, 28.6 (3C), 24.8, 14.9; HRMS (EI): MH+ found 335.1967. C18H26N2O4 requires 335.1971.

Reference： [1]Tetrahedron,2012,vol. 68,p. 1417 - 1421

5
[ 927-80-0 ]
[ 25015-63-8 ]
[ 1201905-61-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	With Schwartz's reagent; In hexane; dichloromethane; at 0 - 20℃; for 18h;	Preparation 29: (£)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane A solution of ethoxyethyne (60% w/w in hexanes, 30 mL, 154 mmol) in DCM (230 mL) was cooled at 0C and pinacol borane (27 mL, 186 mmol) was added followed by Cp2Zr(H)CI (1 .96 g, 7.60 mmol). The mixture was allowed to reach room temperature and stirred for 18 hours. The reaction was filtered through a pad of neutral alumina eluting with 1 0% EtOAc in cyclohexane to afford the title compound (27.66 g, 91 %). 1 H NMR (500 MHz, CDCI3) : delta 7.05 (d, J = 14.4 Hz, 1 H), 4.45 (d, J = 14.4 Hz, 1 H), 3.86 (q, J = 7.1 Hz, 2H), 1 .30 (t, J = 7.1 Hz, 3H), 1 .27 (s, 12H).
82%	With Schwartz's reagent; In hexane; dichloromethane; at 0 - 20℃;Inert atmosphere;	Under an atmosphere of nitrogen in a round bottom flask ethoxyethyne, 50% solution in hexanes (100 g, 710 mmol) and DCM (996 mL) were stirred at about 0 - 5 C. To the stirred solution was added 4,4,5,5-tetramethyl-l,3,2-dioxaborolane (113 mL, 781 mmol) in one portion followed by the addition of bis(cyclopentadienyl)zirconium hydridochloride (9.16 g, 35.5 mmol) at about 0 - 5 C. The suspension (orange) was allowed to gradually warm to room temperature over about 30 min. Dissolution occurred within about 10 min. The reaction mixture was stirred at RT overnight (very dark red). To the reaction solution was added ether (2L) and the solution was washed with saturated aqueous NH4CI. The solvents were removed under reduced pressure, minimal DCM (100 mL) was added and the solution was filtered through a pad of alumina, topped with Celite. The alumina was washed with DCM and the filtrate solvent was removed in vacuo to yield (£)-2-(2-ethoxyvinyl)- 4,4,5,5-tetramethyl-l,3,2-dioxaborolane (114.9 g, 82 %) as a very dark red oil. NMR (400 MHz, OMSO-d6) delta 7.05 (d, 1 H), 4.45 (d, 1 H), 3.83 (q, 2 H), 1.30 (t, 3 H), 1.28 (s, 12 H).
81%	With Schwartz's reagent; In hexane; dichloromethane; at 0 - 20℃; for 16h;Inert atmosphere;	To a cooled solution of ethoxyethyne (ca. 40% w/w solution in hexanes, 5.69 g, 32.47 mmol, 1.3 equiv) in CH2Cl2 (70 mL) was added 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.62 mL, 24.98 mmol, 1 equiv) at 0 C followed by Cp2ZrHCl (387 mg, 1.50 mmol, 0.06 equiv) under N2. After 5 min the reaction mixture was allowed to warm up to room temperature and stirred at this temperature for 16 h then solvents were removed in vacuo. The crude material was purified by column chromatography using a gradient elution (heptane/EtOAc, 9:1 to 8:1) to furnish (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 7 (4.01 g, 81%) as a colourless liquid; Rf=0.40 (heptane/EtOAc, 9:1); 1H NMR (300 MHz): delta 7.03 (d, J=14.6, 1H), 4.43 (d, J=14.6, 1H), 3.84 (q, J=6.9, 2H), 1.30 (t, J=6.9, 3H), 1.26 (s, 12H); 13C NMR (75 MHz): delta 163.1, 87.6 (br s), 82.8 (2C), 64.5, 25.0 (4C), 14.8.

78.13%	zirconocene dichloride; In dichloromethane; at 0 - 25℃; for 16h;	(E)-2- -Ethoxwinyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (100G):Di(cyclopenta-2,4-dien-l-yl)zirconium(IV) chloride (0.685 g, 2.344 mmol) was added to a solution of 4,4,5,5-tetramethyl-l,3,2-dioxaborolane (5.0 g, 39.1 mmol) in dichloromethane (15 mL) followed by ethoxyethyne (3.01 g, 43.0 mmol) at 0 C, and the mixture was stirred for 16 h at 25 C. Insoluble solids were filtered off, and filtrate was concentrated. Residue was partitioned between ethyl acetate and water. Organic layer was separated, washed with brine, dried over sodium sulphate, filtered and concentrated in vacuo to afford title compound (6.04 g, 78.13%) as oil. 1H NMR (400 MHz, CDC13): delta 7.04 (d, J - 14.0 Hz, 1H), 4.43 (d, J= 14.8 Hz, 1H), 3.84 (q, J= 7.2 Hz, 2H), 1.32-1.2 (m, 15H).
	With Schwartz's reagent; In dichloromethane; at 0 - 20℃; for 12h;	To a stirred solution of ethoxyethyne (2.5 g, 35.7 mmol, 1 equiv) in DCM (60 ml) at 0C was added 4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (5.69 ml, 39.2 mmol, 1 .1 equiv) and Bis(cyclopentadienyl)Zirconium (IV) chloride hydride (0.55 g, 2.14 mmol, 0.06 eq). The reaction mixture was stirred at room temperature for 12 h. After consumption of the starting material, the reaction mixture was filtered through a pad of neutral alumina topped with a layer of celite and washed with DCM (50ml). The filtrate obtained was evaporated under vacuum to obtain crude (E)-2-(2-ethoxyvinyl)-4, 4, 5, 5-tetramethyl-1 ,3,2-dioxaborolane as a brown liquid (6.5 g). NMR (400 MHz, CDCI3) delta ppm 1 .25 (s, 12H), 1 .25 - 1 .29 (m, 3H), 3.81 - 3.91 (m, 2H), 4.43 (d, J = 14.4 Hz, 1 H), 7.03 (d, J = 14.8 Hz, 1 H).

Reference： [1]Patent: WO2014/37750,2014,A1 .Location in patent: Paragraph 0042-0045
[2]Patent: WO2016/198908,2016,A1 .Location in patent: Page/Page column 359
[3]Tetrahedron,2012,vol. 68,p. 1417 - 1421
[4]Patent: WO2012/162129,2012,A1 .Location in patent: Page/Page column 102-103
[5]Patent: WO2018/15879,2018,A1 .Location in patent: Page/Page column 120

6
[ 109-92-2 ]
[ 25015-63-8 ]
[ 1201905-61-4 ]
[ 219489-07-3 ]

Yield	Reaction Conditions	Operation in experiment
	palladium diacetate; at 20℃; for 20h;	Example 9Pinacol vinylboronate (6)mixture of E,Z isomers10(E)-6, (Z)-6 Pinacolborane (10) and 4.1 equivalents of ethyl vinylether are stirred at room temperature in the presence of 0.05 mol% Pd(OAc)2 until reaction completion (20 h). The mixture is then concentrated and the product distilled under vacuum to afford pinacol vinylboronate (6) as a colorless liquid in 83% yield. The product consists of a mixture of E/Z isomers (ratio ca. 2:1 ). MS (Turbo Spray): 199 (M+H+, 100%), 216 (M+NH4+).
	With palladium diacetate; at 20℃; for 18h;	To a mixture of pinacolborane (20 g, 156 mmol) and ethyl vinyl ether (61.4 mL, 640 mmol) was added palladium(II) acetate (0.176 g, 0.781 mmol) carefully due to an exothermic process. The reaction mixture was stirred at room temperature for 18 h. Then the reaction mixture was concentrated in vacuo and the residue was passed through a silica plug (0-10% EtOAc in hexanes) to give the product (24.6 g, 85%) as a yellow liquid. UPLC-MS (Acidic Method, 2 min): rt 0.92 and 1.03 min, m/z 199.2 [M+H]+. 1H NMR (400 MHz, CDCl3): d ppm (Note: a mixture of E:Z isomers 1.25: 1) 7.03 (d, 7=14.4 Hz, 1.25H), 6.64 (d, 7=0.4 Hz, 1H), 4.43 (d, 7=14.4 Hz, 1.25H), 4.1 1 (dd, 7=7.8, 4.4 Hz, 1H), 3.94 (q, 7=7.1Hz, 2H), 3.84 (q, 7=7.1Hz, 2.5H), 1.28 - 1.24 (m, 31H), 0.95 - 0.84 (m, 3H).

Reference： [1]Patent: WO2012/10538,2012,A2 .Location in patent: Page/Page column 30-31
[2]Patent: WO2020/106308,2020,A1 .Location in patent: Paragraph 0222

7
[ 5177-27-5 ]
[ 1201905-61-4 ]
[ 1201905-71-6 ]

Yield	Reaction Conditions	Operation in experiment
12.32%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; dipotassium hydrogenphosphate;palladium diacetate; In water; acetonitrile; at 80℃; for 16h;Inert atmosphere;	fE)-2-Chloro-4-f2-ethoxwinyl)Pyrimidin-5-amine (00Eta):A mixture of <strong>[5177-27-5]2,4-dichloropyrimidin-5-amine</strong> (2.0 g, 12.2 mmol), product of Example 100G (6.04 g, 30.5 mmol), potassium phosphate dibasic (5.31 g, 30.5 mmol), palladium(II) acetate (0.027 g, 0.122 mmol) and dicyclohexyl-(2',6'-dimethoxy-[l,l '- biphenyl]-2-yl)phosphine (0.050 g, 0.122 mmol) in acetonitrile (30 mL) and water (20 mL) under argon was refluxed at 80 C for 16 h. The reaction mixture was cooled, diluted with ethyl acetate, and washed with water (2x30 mL) and saturated aqueous brine. The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated and purified by flash chromatography using 30% ethyl acetate in hexane to afford title compound (0.3 g, 12.32%) as an oil. 1H NMR (300MHz, CDC13): delta 7.89 (s, 1H), 7.85 (d, J = 11.7 Hz, 1H), 5.69 (d, J = 11.7 Hz, 1H), 4.05 (q, J = 7.2 Hz, 2H), 3.49 (bs, 2H), 1.37 (t, J = 7.5 Hz, 3H).

Reference： [1]Patent: WO2012/162129,2012,A1 .Location in patent: Page/Page column 103

8
[ 1201905-61-4 ]
[ 1422982-34-0 ]
[ 1422982-58-8 ]

Yield	Reaction Conditions	Operation in experiment
72%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; at 100℃;Inert atmosphere;	To a solution of 5-bromo-N-(1-(3-cyanobenzyl)-1H-pyrazol-4-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carboxamide (1.0 g, 1.8 mmol) in dioxane (100 mL) was added <strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (435 mg, 2.18 mmol), Pd(PPh3)2Cl2 (165 mg, 0.18 mmol), and K2CO3 (497 mg, 3.6 mmol). After the mixture was stirred at 100 C under N2 overnight, the starting material was consumed as indicated by TLC. It was cooled to r.t., filtered, concentrated and purified by column chromatography (PE : EtOAc = 1 : 1 to 1 :2) to give (E)-N-(1-(3-cyanobenzyl)-1H-pyrazol-4-yl)-5-(2-ethoxyvinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carboxamide (700 mg, 72%). The enol ether was diluted in EtOH (50 mL) and cone. HCl (3.0 mL) was added. After the reaction mixture was stirred at r.t. for 3 h, starting material was consumed as indicated by TLC. Saturated NaHCO3 solution was added until pH = 8-9. It was extracted with EtOAc (50 mL x 3) and concentrated to give N-(1-(3-cyanobenzyl)-1H-pyrazol-4-yl)-5-(2-oxoethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carboxamide which was used without further purification (400 mg, 60%). To a solution of this aldehyde in MeOH (30 mL), was added NaBH 4 (45 mg, 1.1 mmol) and the mixture was stirred at r.t. overnight. After majority of the starting material was consumed as indicated by TLC, saturated NaHCO3 (30 mL) was added and it was extracted with EtOAc (50 mL x 2) and concentrated to give N-(1-(3-cyanobenzyl)-1H-pyrazol-4-yl)-5-(2-hydroxyethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carboxamide without further purification (280 mg, 69%). To a solution of this alcohol in EtOH (20 mL) was added cone. HCl (2.0 mL). After the mixture was heated at reflux for 5 h, starting material was consumed as indicated by TLC. It was concentrated and purified by automated reverse-phase HPLC to give the titled compound as white solid (11.5 mg, 5.5%). 1H NMR (MeOD, 400 MHz) delta 8.21 (s, 1H), 8.11 (s, 1H), 7.78 (s, 1H), 7.68 -7.66 (m, 1H), 7.62, (s, 1H), 7.55 (m, 2H), 7.52 (d, J= 8.4 Hz, 1 H), 7.34 (dd, J= 8.4, 1.6 Hz, 1H), 5.41 (s, 2H), 3.81 (t, J= 7.2 Hz, 2H), 2.98 (t, J = 7.2 Hz, 2H). MS: m/z = 387.1 (M+H) +

Reference： [1]Patent: WO2013/24011,2013,A1 .Location in patent: Page/Page column 96

9
[ 1201905-61-4 ]
[ 1423130-38-4 ]
[ 1360056-34-3 ]

Yield	Reaction Conditions	Operation in experiment
69.6%		A 500 mL round-bottomed flask was charged with 2-bromo-N-tert-butyl-4-(2-cyanopropan-2-yl)-6-fluorobenzamide (34.5 g, 101 mmol, 1 equiv.) and potassium carbonate (27.9 g, 202 mmol, 2 equiv.) and the flask was subsequently purged with nitrogen (3 times). 1,4-dioxane (242 ml) and water (34.5 ml) were added. The <strong>[1201905-61-4]E-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (28.0 g, 142 mmol, 1.4 equiv.) was then added by syringe. The reaction mixture was heated to 40C. To the mixture was added bis(dibenzylideneacetone)palladium (2.33 g, 4.04 mmol, 0.04 equiv.) and tricyclohexylphosphine (2.27 g, 8.09 mmol, 0.08 equiv.) and the resulting mixture was heated with stirring at 90C (inner temperature). 100 C (bath) for 2 h until reaction was complete. The reaction mixture was cooled to ambient temperature and quenched with 20% NaHSO3 solution (150 mL) followed by stirring for 2 hr. The mixture was extracted with EtOAc (2 times), dried over MgSO4, and concentrated under reduced pressure. The resultant product was dissolved with TFA (138 ml) in a 350 mL pressured bottle and heated to 100C (bath temp.) for 3 hr. The reaction mixture was transferred to a round-bottomed flask with toluene, and the TFA was removed under reduced pressure, then basified with 20% K2CO3 solution. The reaction mixture was extracted with EtOAc and then with DCM. Crystallization from methyl-tert-butylether afforded 2-(8-fluoro-1-oxo-1,2-dihydroisoquinolin-6-yl)-2-methylpropanenitrile (16.2 g, 69.6 % yield) as a brown solid. 1H NMR (300 MHz, DMSO-d6) delta ppm 1.74 (s, 6 H) 6.60 (dd, J=6.99, 1.70 Hz, 1 H) 7.16 - 7.28 (m, 1 H) 7.36 (dd, J13.03, 1.70 Hz, 1 H)7.61 (d,J=1.89Hz, 1 H) 11.31 (br. s., 1 H).

Reference： [1]Patent: WO2013/24078,2013,A1 .Location in patent: Page/Page column 119

10
[ 1201905-61-4 ]
[ 1426670-17-8 ]
[ 1426670-31-6 ]

Yield	Reaction Conditions	Operation in experiment
77%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium hydroxide; In acetonitrile; at 80℃;Inert atmosphere;	6-(4-(2-(dimethylamino)ethyl)phenyl)-5-ethyl-4-hydroxy-2-oxo-l,2-dihydropyridine-3- carboxylic acid (Cpd 343)Step 1. (E)-methyl l-(2,4-dimethoxybenzyl)-6-(4-(2-ethoxyvinyl)phenyl)-5-ethyl-4- hydroxy-2-oxo-l,2-dihydropyridine-3-carboxylateMethyl 6-(4-chlorophenyl)- 1 -(2,4-dimethoxybenzyl)-5-ethyl-4-(methoxymethoxy)-2- oxo-l,2-dihydropyridine-3-carboxylate from Example 35, Step 1 (0.26 g, 0.5 mmol) was mixed with (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (0.2 g, 1.0 mmol),Pd(OAc)2 (0.0067 g, 6 mol%), S-Phos (0.031 g, 15 mol%) and KOH (0.11 g, 1.0 mmol) in acetonitrile (5 mL). The mixture was degassed by purging the reaction flask under vacuum, then backfilling with Argon (3x). The reaction mixture was heated at 80 C with vigorous magnetic stirring overnight. After cooling to room temperature, the mixture was filtered and the solids were washed with EtOAc. The filtrate was concentrated and purified by chromatography on silica gel (0-100% EtOAc in hexanes) to afford the product as a yellow solid (0.21 g, 77%).XH NMR (500 MHz, Acetone-if) delta ppm 0.91 (t, J= 7 Hz, 3H), 1.31 (t, J= 7 Hz, 3H), 2.14 (q, J= 7 Hz, 2H), 3.56 (s, 3H), 3.77 (s, 3H), 3.92 (s, 3H), 3.96 (q, J= 7 Hz, 2H), 4.86 (s, 2H), 5.91 (d, J= 13 Hz, 1H), 6.38 (d, J= 3 Hz, 1H), 6.46 (dd, J= 8, 3 Hz, 1H), 6.75 (d, J= 8 Hz, 1H), 6.97 (d, J= 8 Hz, 2H), 7.27-7.31 (m, 3H). LC-MS 494.3 [M+H]+, RT 1.62 min.

Reference： [1]Patent: WO2013/33240,2013,A1 .Location in patent: Page/Page column 182

11
[ 1201905-61-4 ]
[ 1447363-86-1 ]
[ 1447363-87-2 ]

Yield	Reaction Conditions	Operation in experiment
97.1 mg	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; water; at 100℃;Inert atmosphere;	Step 2: In a 10 ml round bottom flask equipped with a magnetic stir bar and a nitrogen inlet, the 2-chloro-5-nitro-4-(4-o-tolyl-piperazin-1 -yl)-benzoic acid methyl ester 10a (1 15.70 mg, 0.30 mmol) was combined dry with the tricyclohexylphosphine (20.00 mg, 0.07 mmol) and was then taken up in clean, dry 1 ,4-dioxane (0.75 ml, 8.77 mmol) and the mixture was stirred at room temperature under nitrogen atmosphere until all solids were in solution. While that was stirring, the potassium phosphate tribasic (126.00 mg, 0.59 mmol) was dissolved in water (0.50 ml, 27.75 mmol) and once complete dissolution was achieved, the basic solution was added to the stirring dioxane solution. The reaction mixture was then placed under vacuum for 10 min and was then flushed with nitrogen. The 2-((E)-2-ethoxy-vinyl)-4,4,5,5-tetramethyl- [1 ,3,2]dioxaborolane (64.60 mg, 0.33 mmol) was added to the solution, and the system was degassed once more. After flushing the system with nitrogen once more, the tris(dibenzylideneacetone)dipalladium (27.00 mg, 0.03 mmol) was added in one portion and the flask was fitted with a jacketed reflux condenser and the system was purged under vacuum once more. The reaction mixture system was then flushed with nitrogen and warmed to 100C. The reaction was allowed to stir overnight under nitrogen at elevated temperatures. The reaction was cooled to room temperature and the mixture was filtered through Celite, washing heavily with ethyl acetate. The liquid filtrate was then collected and the solvent was removed under reduced pressure, absorbing the residue onto Celite. The product was then purified using silica gel column chromatography, eluting a gradient of 100% heptanes to 75% ethyl acetate in heptane. The product 2-((E)-2-ethoxy-vinyl)-5-nitro-4-(4-o-tolyl-piperazin-1 -yl)- benzoic acid methyl ester 10b (97.10 mg, 0.23 mmol), was isolated as an off-white, slightly yellowish solid. LCMS (m/e) = 426 (M+H).

Reference： [1]Patent: WO2013/106409,2013,A1 .Location in patent: Page/Page column 76-77

12
[ 3934-20-1 ]
[ 1201905-61-4 ]
[ 1434180-02-5 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 7025 - 7048

13
[ 1201905-61-4 ]
[ 1513860-25-7 ]
[ 1513860-26-8 ]

Yield	Reaction Conditions	Operation in experiment
	With di-mu-bromobis(tri-tert-butylphosphino)dipalladium(I); sodium carbonate; In 1,4-dioxane; water; at 95℃;Inert atmosphere;	Step 2: 7-(2, 6-d ifluoro-3 , 5-dimethoxyphenyl)-2-[(E)-2-ethoxyvinylJ-9, 9-dimethyl-3- (phenylsufonyl)-3, 6, 7 9-tetra hydro-8H-pyrrolo[2 , 3-cJ-2, 7-nap hthyridin-8-one To a mixture of 2-bromo-7-(2,6-difluoro-3 ,5-dimethoxyphenyl)-9,9-dimethyl-3 -(phenylsulfonyl)-3 ,6,7,9-tetrahydro-8H-pyrrolo[2,3 -c] -2,7-naphthyridin-8-one (0.10 g, 0.16mmol), 2- [(E)-2-ethoxyvinyl]-4,4,5,5-tetramethyl- 1,3 ,2-dioxaborolane (Aldrich, cat 731528:0.033 g, 0.16 mmol) and sodium carbonate (0.035 g, 0.33 mmol) in 1,4-dioxane (1 mL, 10mmol)/water (0.2 mL, 10 mmol) was added dichloro(bis {di-tert-butyl[4-(dimethylamino)phenyl]phosphoranyl})palladium (3.5 mg, 0.0049 mmol). The mixture was evacuated then refilled with N2 for three times. The reaction mixture was then stirred at 95C for overnight then cooled to room temperature and diluted with DCM. The mixture was washed with water and brine. The organic layer was dried over Na2SO4 and concentrated.The residue was purified by column eluted with 0 to 10 % EtOAc/DCM to give the desired product.

Reference： [1]Patent: WO2014/7951,2014,A2 .Location in patent: Page/Page column 232

14
[ 1201905-61-4 ]
[ 50593-91-4 ]
[ 1578245-93-8 ]

Yield	Reaction Conditions	Operation in experiment
63%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In tetrahydrofuran; water; at 65℃; for 18h;	Preparation 31 : (£)-methyl 5-(2-ethoxyvinyl)-2-(methylthio)pyrimidine-4-carboxylate A solution of (£)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (Preparation 29, 4.34 g, 21 .91 mmol), <strong>[50593-91-4]methyl 5-bromo-2-(methylthio)pyrimidine-4-carboxylate</strong> (Preparation 30, 3.81 g, 14.48 mmol) and Pd(dppf)CI2 DCM (505 mg, 0.618 mmol) was dissolved in THF (45 mL) and 2M sodium carbonate in water (15 mL) and heated to 65 C for 18 hours. The mixture was diluted with EtOAc and quenched with brine. The aqueous layer was extracted with EtOAc three times. The combined organic layers were washed with water and brine, dried and concentrated. The residue was purified by silica gel column chromatography eluting with 0 to 10% EtOAc in cyclohexane to give the title compound (2.30 g, 63%). 1 H NMR (500 MHz, CDCI3) : delta 8.67 (s, 1 H), 6.96 (d, J = 13.1 Hz, 1 H), 6.26 (d, J = 13.1 Hz, 1 H), 4.13 - 3.81 (m, 5H), 2.60 (s, 3H), 1 .37 (t, J = 7.0 Hz, 3H). LCMS (ESI) Rt = 2.49 minutes MS m/z 255 [M+H]+

Reference： [1]Patent: WO2014/37750,2014,A1 .Location in patent: Paragraph 00149; 0051-0055
[2]Organic and Biomolecular Chemistry,2015,vol. 13,p. 893 - 904

15
[ 1222090-62-1 ]
[ 1201905-61-4 ]
[ 1578246-51-1 ]

Yield	Reaction Conditions	Operation in experiment
82%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 70℃; for 18h;Inert atmosphere;	Preparation 85: (E)-methyl 2-(benzyloxy)-5-(2-ethoxyvinyl)isonicotinate To a suspension of methyl 2-(benzyloxy)-5-bromoisonicotinate (Preparation 84, 1 .5 g, 4.66 mmol), (E)-2-(2-ethoxyvinyl)-4, 4, 5, 5-tetramethyl-1 ,3,2-dioxaborolane (Preparation 29, 1 .844 g, 9.31 mmol) and Na2C03 (0.99 g, 9.31 mmol) in toluene (5 ml_), EtOH (5 ml_) and water (5 ml_) was added Pd(PPh3)4 (377 mg, 0.326 mmol). The reaction mixture was heated to 70C for 1 8 hours, under nitrogen. The reaction mixture was diluted with EtOAc (75 ml_) and water (75 ml_). The organic layer was dried (MgS04) and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 0-1 0% EtOAc in cyclohexane to give the title compound (1 .2 g, 82%). 1 H NMR (500 MHz, CDCI3): delta 8.23 (s, 1 H), 7.47 (d, J = 7.5, 1 .5 Hz, 2H), 7.39 (td, J = 8.5, 2.5 Hz, 2H), 7.33 (m, 1 H), 7.24 (s, 1 H), 6.80 (d, J = 13.0 Hz, 1 H), 6.39 (d, J = 13.0 Hz, 1 H), 5.40 (s, 2H), 3.95 (q, J = 7.5 Hz, 2H), 3.92 (s, 3H), 1 .37 (t, J = 7.5 Hz, 3H). LCMS (ESI) Rt = 3.09 minutes MS m/z 314.27 [M+H]+

Reference： [1]Patent: WO2014/37750,2014,A1 .Location in patent: Paragraph 00149; 00221; 00222

16
[ 1201905-61-4 ]
[ 1613719-76-8 ]
[ 1613720-55-0 ]

Yield	Reaction Conditions	Operation in experiment
51%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 100℃;	To a solution of tert-butyl 3-((8-bromo-1-methyl-2-oxo-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylate (Example 1, Step B, 0.20 g, 0.43 mmol), <strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (0.1 g, 0.5 mmol) in dioxane (6 mL) and water (1 mL) was added PdCl2(dppf)-CH2Cl2 adduct (0.035 g, 0.043 mmol) and K2CO3 (0.118 g, 0.85 mmol). The reaction mixture was stirred at 100 C. overnight. The reaction mixture was cooled to ambient temperature, the solvent was removed in vacuo and the residue was purified by chromatography on silica gel (eluting with 2% MeOH in DCM) to give (E)-tert-butyl 3-((8-(2-ethoxyvinyl)-1-methyl-2-oxo-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylate (0.10 g, 51%) as a yellow solid. LC/MS (Table 1, Method 2) Rt=1.352 min.; MS m/z: 458 [M+H]+.

Reference： [1]Patent: US2014/206663,2014,A1 .Location in patent: Paragraph 1228; 1229

17
[ 1201905-61-4 ]
[ 1613721-10-0 ]
[ 1613721-11-1 ]

Yield	Reaction Conditions	Operation in experiment
72%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 80℃;	A mixture of 3-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (12.7 g, 26.4 mmol), <strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (7.85 g, 39.7 mmol), Pd(dppf)Cl2.CH2Cl2 adduct (4.32 g, 5.29 mmol) and K2CO3 (7.31 g, 52.9 mmol) in dioxane (210 mL) and water (35 mL) was stirred at 80 C. overnight. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 20-50% EtOAc in petroleum ether) to give 3-[(R)-7-((E)-2-ethoxy-vinyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (9 g, 72%). 1H NMR (CD3OD, 400 MHz): delta 6.88 (s, 1H), 6.81 (d, J=12.5 Hz, 1H), 5.99 (brs, 1H), 5.85 (d, J=12.5 Hz, 1H), 4.97-4.93 (m, 1H), 4.70 (m, 2H), 4.06 (m, 2H), 3.93 (m, 4H), 1.61 (s, 3H), 1.48-1.44 (m, 12H), 1.33 (s, 3H).

Reference： [1]Patent: US2014/206663,2014,A1 .Location in patent: Paragraph 1454; 1455

18
[ 256935-85-0 ]
[ 1201905-61-4 ]
[ 1616257-23-8 ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; potassium hydroxide; In acetonitrile; at 70℃; for 1h;Inert atmosphere; Sealed tube;	To a mixture of methyl 4-amino-2-chloro-5-iodobenzoate (1.05 mmol), KOH (2.1 mmol) Pd(OAc)2 (0.03 mmol) and 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (0.08 mmol) was added under argon CH3CN (10 mL) and trans-2-ethoxyvinylboronic acid pinacol ester (2.1 mmol). The mixture was stirred for 1 h at 70C in a sealed vial, quenched with a 10% solution of NH4CI and extracted three times with DCM. The organic phases were dried over MgS04 and concentrated in vacuo. The crude was purified by CC (SNAP KP-Sil from Biotage) using Hept/EtOAc from 100/0 to 27/63 to give the title compound as brown oil. LC-MS (A): tR = 0.85 min; [M+CH3CN+H]+: 297.04

Reference： [1]Patent: WO2014/97140,2014,A1 .Location in patent: Page/Page column 104

19
[ 1201905-61-4 ]
[ 148493-37-2 ]
[ 1621706-14-6 ]

Yield	Reaction Conditions	Operation in experiment
89%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 3h;Inert atmosphere;	To a 1 necked round bottom flask, with stirrer, and air condenser, under nitrogen, is added <strong>[148493-37-2]2,6-dichloro-3-iodo-pyridine</strong> (1.0 g, 3.8 mmol), 2- [(E)-2-ethoxyvinyl]-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (0.9 g, 4.8 mmol), CS2CO3 (3.75 g, 11.5 mmol), l,4-dioxane (19.2 mL), and water (4.26 mL). This reaction mixture is purged 3 times alternating between vacuum and nitrogen, and [l,T bis(diphenylphosphino) ferrocene]dichloropalladium(II) (0.2 g) is added. The resulting mixture is stirred for 3 hr at 90 C, the reaction is poured onto saturated aqueous NH4Cl, and the aqueous mixture is extracted three times with EtOAc. The combined organic extracts are dried over MgS04, filtered, and the filtrate is concentrated under reduced pressure. The resulting residue is purified by flash chromatography over silica gel, eluting with a gradient of 0-100% EtOAc in cyclohexane, to afford the title compound (748 mg, 89% yield), after solvent evaporation of the desired chromatographic fractions. NMR (300 MHz, CDCh): d 1.37 (m, 3H), 3.97 (m, 2H), 5.97 (m, 1H), 6.99 (m, 1H), 7.16 (m, lH),7.60 (m, 1H).
86%	With dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); caesium carbonate; In 1,4-dioxane; water; at 70℃;Inert atmosphere;	To a degassed solution of <strong>[148493-37-2]2,6-dichloro-3-iodopyridine</strong> (3.0 g, 11 mmol) and (E)2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.2 g, 11 mmol) in 1,4- dioxane (20 mL) and water (1.0 mL) was added CS2CO3 (7.1 g, 22 mmol) and 1,1?-bis(di-tert- butylphosphino)ferrocene palladium chloride (357 mg, 0.54 mmol) under N2 protection. The resulting mixture was heated to 70 C and stirred at this temperature overnight. The reaction was cooled, filtered through a pad of the celite and washed with ethyl acetate. The combined filtrate was evaporated in vacuo. The resulting residue was purified using column chromatography (eluted with 0-20% EtOAc / DCM) to provide (E)-2,6-dichloro-3-(2-ethoxyvinyl)pyridine (1.96 mg, yield: 86%). MS (M+H): 218.
86%	With 1,1'-bis(di-tert-butylphosphino)ferrocene-dichloropalladium(II); caesium carbonate; In 1,4-dioxane; water; at 70℃;Inert atmosphere;	To a degassed solution of<strong>[148493-37-2]2,6-dichloro-3-iodopyridine</strong> (3.0 g, 11 mmol) and (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.2 g, 11 mmol) in 1,4- dioxane (20mL) and water (1.0 mL) was added CS2C03 (7.1 g, 22 mmol) and 1, 1'-bis(di-tertbutylphosphino)ferrocene palladium chloride (357 mg, 0.54 mmol) under N2 protection. The resulting mixture was heated to 70 oc and stirred at this temperature overnight. The reactionwas cooled, filtered through a pad of the celite and washed with ethyl acetate. The combinedfiltrate was evaporated in vacuo. The resulting residue was purified using columnchromatography (eluted with 0-20% EtOAc I DCM) to provide (E)-2,6-dichloro-3-(2-5 ethoxyvinyl)pyridine (1.96 mg, yield: 86%). MS (M+Ht: 218.

Reference： [1]Patent: WO2019/245907,2019,A1 .Location in patent: Page/Page column 21-22
[2]Patent: WO2014/123793,2014,A1 .Location in patent: Page/Page column 128; 129
[3]Patent: WO2014/121416,2014,A1 .Location in patent: Page/Page column 128; 129

20
[ 1201905-61-4 ]
[ 1138444-17-3 ]
[ 1621706-09-9 ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 73℃; for 20.25h;Inert atmosphere;	To a mixture of <strong>[1138444-17-3]6-bromo-2-chloro-3-iodopyridine</strong> (8.0 g, 25.1 mmol), (E)-2-(2- ethoxyvinyl)-4,4,5 ,5-tetramethyl- 1,3 ,2-dioxaborolane (4.98 g, 25.1 mmol), cesium carbonate (16.38 g, 50.3 mmol), and [1,1 ?-bis(diphenylphosphino)ferrocene] dichloropalladium(II) (2.052,2.51 mmol) was added 1,4-dioxane (100 mL) and H20 (10 mL). A steady stream of N2 was bubbled through the reaction mixture for 15 minutes then the mixture was heated to 73 C for 20h. The mixture was cooled to ambient temperature, diluted with EtOAc, and washed successively with H20 (2X) and brine (lx). The organic layer was dried over MgSO4, filtered,and concentrated in vacuo. The residue was purified by silica gel column chromatography using a step gradient of 0-10-60% EtOAc/Hexanes as eluent. MS (M+H): 261.
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 73℃; for 20h;Inert atmosphere;	To a mixture of <strong>[1138444-17-3]6-bromo-2-chloro-3-iodopyridine</strong> (8.0 g, 25.1 mmol), (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4.98 g, 25.1 mmol), cesium carbonate(16.38 g, 50.3 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (2.052,2.5I mmol) was added I,4-dioxane (IOO mL) and H20 (IO mL). A steady stream ofN2 wasbubbled through the reaction mixture for I5 minutes then the mixture was heated to 73 oc for 20h. The mixture was cooled to ambient temperature, diluted with EtOAc, and washedsuccessively with H20 (2X) and brine (IX). The organic layer was dried over MgS04, filtered,5 and concentrated in vacuo. The residue was purified by silica gel column chromatography usinga step gradient ofO-I0-60% EtOAc/Hexanes as eluent. MS (M+H): 261.

Reference： [1]Patent: WO2014/123793,2014,A1 .Location in patent: Page/Page column 122; 123
[2]Patent: WO2014/121416,2014,A1 .Location in patent: Page/Page column 122; 123

21
[ 1201905-61-4 ]
methyl 4-(5-bromo-4-methylthiazol-2-yl)-1-methyl-1H-pyrazol-5-carboxylate [ No CAS ]
(E)-methyl 4-(5-(2-ethoxyvinyl)-4-methylthiazol-2-yl)-1-methyl-1H-pyrazol-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31 mg	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In water; acetonitrile; at 90℃; for 2h;Inert atmosphere;	<strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (63 mg), palladium acetate (7.1 mg), tripotassium phosphate (67 mg), 2-dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl (26 mg), and water (0.35 ml) were added to an acetonitrile (4.0 ml) solution of the methyl 4-(5-bromo-4-methylthiazol-2-yl)-1-methyl-1H-pyrazole-5-carboxylate (50 mg) obtained in (Example 5:11) <Step 1>, and the obtained mixture was then stirred under heating in a nitrogen atmosphere for 2 hours at 90 C. Thereafter, ethyl acetate (50 ml) and a saturated sodium hydrogen carbonate aqueous solution (30 ml) were added to the reaction solution. After extraction of organic layers, water layers were extracted with ethyl acetate (50 ml). The organic layers were combined. The combined organic layer was washed with a saturated saline, and was then dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the obtained residue was then purified by silica gel column chromatography (silica gel: eluent; heptane:ethyl acetate=92:8-40:60), so as to obtain the title compound (31 mg) in the form of a yellow solid.

Reference： [1]Patent: US2014/378447,2014,A1 .Location in patent: Paragraph 0842

22
[ 1201905-61-4 ]
4-chloro-6-cyclohexyl-2-methylthieno[2,3-d]pyrimidine [ No CAS ]
6-cyclohexyl-4-[(E)-2-ethoxyvinyl]-2-methylthieno[2,3-d]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
885 mg	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 85℃; for 2h;Inert atmosphere;	Preparation Example 14 To a mixture of 4-chloro-6-cyclohexyl-2-methylthieno[2,3-d]pyrimidine (1.0 g) and DMF (40 mL) were added (E)-1-ethoxyethene-2-boronic acid pinacol ester (900 mg) and K3PO4 (4.3 g), and Pd(PPh3)4 (500 mg) was added thereto under an argon atmosphere, followed by heating and stirring at 85 C. for 2 hours. To the reaction mixture was added water, followed by extraction with EtOAc. The organic layer was washed with brine, dried over Na2SO4, then concentrated under reduced pressure, and purified by silica gel column (hexane/EtOAc) to obtain 6-cyclohexyl-4-[(E)-2-ethoxyvinyl]-2-methylthieno[2,3-d]pyrimidine (885 mg).

Reference： [1]Patent: US2015/111876,2015,A1 .Location in patent: Paragraph 0267

23
[ 1201905-61-4 ]
3-bromo-7-((ethyl(4-fluorophenyl)amino)methyl)-2-methyl-5H-thiazolo[3,2-α]pyrimidin-5-one [ No CAS ]
3-[(E)-2-ethoxyvinyl]-7-[(N-ethyl-4-fluoroanilino)methyl]-2-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 3h;Inert atmosphere;	To a solution of 3-bromo-7-[[ethyl(4-fluorophenyl)amino]methyl]-2-methyl-5H- [l,3]thiazolo[3,2-a]pyrimidin-5-one (from Example 5.1, Step 1) (50 mg, 0.13 mmol) in 1 ,4-dioxane/water (0.6/0.2 mL) was added 2-[(i?)-2-ethoxyethenyl]-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (40 mg, 0.20 mmol), potassium phosphate (80 mg, 0.38 mmol) and tetrakis(triphenylphosphine)palladium (20 mg, 0.02 mmol). The resulting solution was stirred for 3 h at 90 C under nitrogen. After cooling down to room temperature, the reaction mixture was concentrated in vacuo. The residue was purified by chromatography with ethyl acetate/petroleum ether (1/5) to afford the title compound as a light yellow solid (16.9 mg, 35%). LCMS (ESI): M+H+ = 388.0; lU NMR: (300 MHz, CDC13): delta 6.93-6.85 (m, 2H), 6.60-6.51 (m, 2H), 6.52-5.48 (m, IH), 6.34-6.19 (m, IH), 6.10 (s, IH), 4.27 (s, 2H), 3.99-3.92 (m, 2H), 3.53-3.42 (m, 2H), 2.38 (s, 3H), 1.38-1.35 (m, 3H), 2.23-2.19 (m, 3H).

Reference： [1]Patent: WO2015/52226,2015,A1 .Location in patent: Paragraph 0288
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 2760 - 2779

24
[ 1201905-61-4 ]
(R)-tert-rutyl 2-(4-chloropyridin-3-yl)pyrrolidine-1-carboxylate [ No CAS ]
tert-butyl (R,E)-2-(4-(2-ethoxyvinyl)pyridin-3-yl)pyrrolidine-1-carboxylate [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 472 - 475

25
[ 1201905-61-4 ]
2-((4-bromo-2,6-difluorobenzyl)thio)-7-(3,4-dimethoxyphenyl)-1-(4-fluorophenyl)-7-methyl-4,5,6,7-tetrahydro-1H-benzo[d]imidazole [ No CAS ]
(E)-7-(3,4-dimethoxyphenyl)-2-((4-(2-ethoxyvinyl)-2,6-difluorobenzyl)thio)-1-(4-fluorophenyl)-7-methyl-4,5,6,7-tetrahydro-1H-benzo[d]imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; toluene; at 100℃; for 2h;Sealed tube;	Example 110: (E)~7~(3,4-dimethoxyphenyl)~2-((4~(2~ethoxyvinyl)~2.6~ difluorobenzyl)thio)-l-(4- rophenyl)-7-methyl-4.5t6, 7-tetrahydro-lH- 2-((4-Bromo-2,6-difluorobenzyl)thio)-7-(3,4-dimethoxyphenyl)-l-(4- fluorophenyl)-7-methyl-4,5,6,7-tetrahydro-lH-benzo[d]ioiidazole (150 mg, 0.25 mniol) and (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-l ,3,2-dioxaborolane (102 mg, 0,50 mniol), Pd(PPh3)4 (28 mg, 0.025 mmol), 2M Na2C03 solution (1 mL) in toluene (2 mL) and EtOH (1 mL) were heated at 100 C in a sealed tube for 2 hours. The reaction was filtered and washed with ethyl acetate. The reaction was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried and concentrated to give the crude product which was then purified by silica gel column chromatography to give the title product as a clolorless oil (1 02 mg, 69%). JH NMR (400 MHz, CDCI3) delta 7.10 (d, J = 7.5 Hz, 2H), 6.75 (t, J = 7.0 Hz, 1H), 6.62 (d, J = 6.5 Hz, 1H), 6.58 (m, 1H), 6.52 (d, J = 6.8 Hz, 2H), 6.25 (m, IH), 6.03 in:. I I I ). 5.68 (d, J = 9.8 Hz, 1H), 5.10 (d, J = 9.5 Hz, 1H), 4.10 (abq, J = 13.0, 9.5 Hz, 2H), 3.89 (q, J = 8.5 Hz, 2H), 3.85 (s, 3H), 3.78 (s, 3H), 2,80 (m, 2H), 1.81 (m, 4H), 1.32 (s, 3H), 1.28 (t, J = 9.3 Hz, M l ).

Reference： [1]Patent: WO2015/160772,2015,A1 .Location in patent: Page/Page column 202-203
[2]ACS Medicinal Chemistry Letters,2017,vol. 8,p. 560 - 565

26
[ 59489-71-3 ]
[ 1201905-61-4 ]
(E)-5-(2-ethoxyvinyl)pyrazin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; at 130℃; for 0.333333h;Microwave irradiation;	Step 1. (E)-5-(2-ethoxyvinyl)pyrazin-2-amine To a solution of 5-bromopyrazin-2-amine (200 mg, 1.149 mmol) in DME (2874 muL) was added <strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (341 mg, 1.724 mmol), PdCl2(dppf)-CH2Cl2 adduct (94 mg, 0.115 mmol), and 2M Na2CO3 (958 muL). The reaction mixture was stirred at 130 C. in microwave reactor for 20 min. The reaction mixture was filtered through Celite and washed with EtOAc, the filtrate was partition between EtOAc and water. The aqueous was extracted by EtOAc three times, the combined organic was dried and concentrated. The crude material was purified by flash chromatography to give (E)-5-(2-ethoxyvinyl)pyrazin-2-amine. LCMS (m/z): 166.1 (MH+), 0.41 min.

Reference： [1]Patent: US9242996,2016,B2 .Location in patent: Page/Page column 132; 133

27
[ 1201905-61-4 ]
6-chloro-4-(1,3-dioxolan-2-yl)-5’-fluoro-2’-methoxy-3,4’-bipyridine [ No CAS ]
(E)-4-(1,3-dioxolan-2-yl)-6-(2-ethoxyvinyl)-5’-fluoro-2’-methoxy-3,4’-bipyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In tetrahydrofuran; water; for 16h;Inert atmosphere; Heating;	Step 3: (E)-4-( 1 ,3-dioxolan-2-yl)-6-(2-ethoxyvinyl)-5?-fluoro-2?-methoxy-3 ,4?-bipyridine To a nitrogen-sparged THF (3 ml) solution of 6-chloro-4-( 1,3 -dioxolan-2-yl)-5 ?-fluoro-2?-methoxy- 3 ,4?-bipyridine (180 mg, 0.579 mmol), (E)-2-(2-ethoxyvinyl)-4,4,5 ,5-tetramethyl- 1,3,2- dioxaborolane (172 mg, 0.869 mmol) and Pd(PPh3)4 (66.9 mg, 0.058 mmol) was added Na2CO3(184 mg, 1.738 mmol) and water (1 mL). The reaction was heated on a heating block. After 16 h, the mixture was poured into saturated NH4C1 (25 mL) and extracted with EtOAc (2 x 25 mL). The combined organic layers were combined, dried (Mg504) and concentrated. The resulting residue was purified by HPLC (ISCO 40 gram, 0 to 50% EtOAc/Hexane gradient) to give the title compound. LC/MS (m/z): 347.5 (M+H).

Reference： [1]Patent: WO2016/22742,2016,A1 .Location in patent: Page/Page column 125

28
[ 1201905-61-4 ]
N-(3-bromo-2,6-dimethylpyridin-4-yl)-2,2-dimethylpropanamide [ No CAS ]
N-{3-[(E)-2-ethoxyethenyl]-2,6-dimethylpyridin-4-yl}-2,2-dimethylpropanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate tribasic trihydrate; palladium diacetate; In water; acetonitrile; for 1h;Reflux; Inert atmosphere;	Step C: //-{3-[(£)-2-Ethoxvethenvn-2,6-dimethvlpvridin-4-vl}-2,2-dimethylpropanamide A deoxygenated mixture of W-(3-bromo-2,6-dimethylpyridin-4-yl)-2,2- dimethylpropanamide (3.00 g, 10.5 mmol), (£)-l-ethoxyethene-2-boronic acid pinacol ester (4.17 g, 21.0 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxy-l,l'-biphenyl (432 mg, 1.05 mmol), palladium(ll) acetate (118 mg, 0.53 mmol) and potassium phosphate tribasic (4.47 g, 21.0 mmol) in CH3CIM (30 mL) and water (20 mL) was heated at reflux for 1 h. The resulting mixture was allowed to cool to ambient temperature, then partitioned between water (30 mL) and CH2CI2 (50 mL). The aqueous layer was extracted further with CH2CI2 (2 x 50 mL) and the combined organic extracts were dried over Na2S04, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with a gradient of CH2CI2:MeOH :NH4OH - 100:0:0 to 80:20:2, to afford the title compound. MS: m/z = 277.2 (M + 1).

Reference： [1]Patent: WO2016/22644,2016,A1 .Location in patent: Page/Page column 99

29
[ 695-17-0 ]
[ 1201905-61-4 ]
5-(2-ethoxyvinyl)-2-methylpyridine [ No CAS ]
(Z)-5-(2-ethoxyvinyl)-2-methylpyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 75℃; for 12h;Inert atmosphere;	[0235] To a solution of <strong>[695-17-0]5-iodo-2-methylpyridine</strong> (1.0 g , 4.5 mmol) and (E)-2-(2-ethoxyvinyl)- 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.8 g, 9.0 mmol) in DME/H20 (24 mL / 6 mL) was added Pd(PPh3)4 (266 mg, 0.23 mmol) and Na2CO3 (965 mg, 9.1 mmol) under nitrogen. The reaction mixture was stirred at 75C for 12 hr and cooled to room temperature. The mixture was concentrated and extracted with EtOAc. The combined organic phases were washed with water, brine, dried over anhydrous Na2504 and concentrated. The residue was purified by column chromatography over silica gel (Hex / EtOAc =20/1) to afford the title compound (400 mg, 54%). as an oil comprising a mixture (cs. 6:5 ratio) of E/Z-isomers 1H NMR (400 MHz, CDCI3) 6 For E-isomer: 8.55 (d, J = 2.0 Hz, 1H), 7.89 (dd, J = 2.0 and 8.0 Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 6.99 (d, J = 12.8 Hz, 1H), 5.75 (d, J = 12.8 Hz, 1H), 3.93 (q, J = 6.8 Hz, 2H),

Reference： [1]Patent: WO2016/126869,2016,A1 .Location in patent: Paragraph 0235

30
[ 873107-98-3 ]
[ 1201905-61-4 ]
(E)-5-(2-ethoxyvinyl)-2-(trifluoromethyl)pyridine [ No CAS ]
(Z)-5-(2-ethoxyvinyl)-2-(trifluoromethyl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 75℃; for 3h;Inert atmosphere;	[0231] To a stirred solution of <strong>[873107-98-3]5-iodo-2-(trifluoromethyl)pyridine</strong> (0.2 g, 0.7 mmol) and (E)-2-(2- ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (290 mg, 1.47 mmol) in DME/H20 (16 mL/ 4 mL) were added Pd(PPh3)4 (42.8 mg, 0.037 mmol) and Na2CO3 (156 mg, 1.47 mmol) under nitrogen. The resulting mixture was stirred at 75 C for 3 hr and allowed to cool to room temperature. The mixture was concentrated and extracted with EtOAc. The combined organic phases were washed with H20, brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography over silica gel (Hex/EtOAc = 20/1) to afford the title compound as an oil (85 mg, 76%) comprising a ca. 70:30 mixture of E/Z isomers.

Reference： [1]Patent: WO2016/126869,2016,A1 .Location in patent: Paragraph 0231

31
[ 1201905-61-4 ]
[ 1996-29-8 ]
1-(2-butoxyvinyl)-4-chloro-2-fluorobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 75℃; for 12h;Inert atmosphere;	[0239] To a stirred solution of 1-bromo-4-chloro-2-fluorobenzene (0.9 g, 4.32 mmol) and (E)-2- (2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.5 g, 7.5 mmol) in DME/H20 (v/v = 4:1, 30 mL) were added Pd(PPh3)4 (218 mg, 0.19 mmol) and Na2CO3(795mg, 7.5 mmol) under nitrogen. The reaction mixture was heated to 75C. After stirring at 75C for 12 hr, the mixture was concentrated and treated with EtOAc. The organic phase was washed with water, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give the coupling product 1-(2-butoxyvinyl)-4-chloro-2-fluorobenzene which was purified by filtration through a pad of silica gel (Hex / EtOAc =20/1) to afford an oil (500 mg, 55%). The above 1-(2-butoxyvinyl)-4-chloro-2-fluorobenzene (200 mg, 0.88 mmol) was dissolved in a mixture of acetone (2 mL) and 3N aqueous HCI (2 mL). The mixture was heated at 40 C under nitrogen for 5 hours, cooled to room temperature and extracted with ether. The organic phase was washed with brine, dried over anhydrous Na2SO4, and concentrated to afford the title compound which was used in the next step without further purification (185mg). 1H NMR (400 MHz, CDCI3) 6 9.76 (s, 1H), 7.16-7.14 (m, 3H), 3.74 (s, 2H).

Reference： [1]Patent: WO2016/126869,2016,A1 .Location in patent: Paragraph 0239

32
[ 1201905-61-4 ]
N-(4-(7-chloro-3-(6-(difluoromethyl)pyridin-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)pyridin-2-yl)acetamide [ No CAS ]
(E)-N-(4-(3-(6-(difluoromethyl)pyridin-2-yl)-7-(2-ethoxyvinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-2-yl)pyridin-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); caesium carbonate; In 1,4-dioxane; water; at 80℃; for 1h;Inert atmosphere; Sealed tube;	A mixture of Example 125B (90.0 mg, 0.165 mmol) and cesium carbonate (216 mg, 0.662 mmol) was evacuated and backfilled with N2, then 1,4-dioxane (1489 muL) and H2O (165 muL) were added. The mixture was sparged with N2 for 5 min, then 2nd generation XPhos precatalyst (6.51 mg, 8.27 mumol) and <strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (98 mg, 0.496 mmol) were added. The mixture was sparged with N2 for 1 min, then it was sealed and stirred at 80 C. for 1 h. The reaction was cooled to room temperature, diluted with EtOAc (30 mL), washed with sat. aq. NaCl (30 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography (24 g silica gel with 5 g prepacked load cartridge; linear gradient 0-100% EtOAc-CH2Cl2) to provide Example 155A (67.2 mg, 70%) as a light yellow solid. LC-MS m/z 580 [M+H]+; 1H NMR (400 MHz, DMSO-d6) delta 10.58 (s, 1H), 8.52 (d, J=8.1 Hz, 1H), 8.40 (d, J=4.9 Hz, 1H), 8.35 (d, J=5.1 Hz, 1H), 8.23 (s, 1H), 8.00 (t, J=7.9 Hz, 1H), 7.44 (d, J=7.7 Hz, 1H), 7.40 (d, J=12.7 Hz, 1H), 7.30 (d, J=5.0 Hz, 1H), 7.11 (dd, J=5.1, 1.5 Hz, 1H), 6.57-6.26 (m, 2H), 5.40 (s, 2H), 4.02 (q, J=7.0 Hz, 2H), 3.37-3.32 (m, 2H), 2.07 (s, 3H), 1.31 (t, J=7.0 Hz, 3H), 0.85-0.75 (m, 2H), -0.09 (s, 9H).

Reference： [1]Patent: US2016/176871,2016,A1 .Location in patent: Paragraph 0753-0754

33
[ 1201905-61-4 ]
8-[(trifluoromethyl)sulfonyl]oxy}-1,4-dioxaspiro[4.5]dec-8-en-7-ylbenzoate [ No CAS ]
C₁₉H₂₂O₅ [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 3798 - 3801

34
[ 1201905-61-4 ]
methyl 4-((4-bromobenzyl)carbamoyl)benzoate [ No CAS ]
(E)-methyl 4-((4-(2-ethoxyvinyl)benzyl)carbamoyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; at 100℃; for 18h;	To a stirred solution of methyl 4-((4-bromobenzyl)carbamoyl)benzoate (1.0 g, 2.87 mmol) in 1,4-dioxane (30 mL) was added (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (0.68 g, 3.45 mmol), potassium carbonate (0.79 g, 5.75 mmol) and bis- (triphenylphosphine) palladium (II) dichloride (0.202 g, 0.29 mmol). The reaction mixture was heated at 100 C for 18 hours. The reaction mixture was diluted with ethyl acetate and washed sequentially with water and brine (x2). ). The organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated at reduced pressure. The residue was purified by column chromatography (eluent 100% i-hexane to 50% ethyl acetate / i-hexane) to afford the title compound (0.499 g, 57%). NMR (400 MHz, DMSO-de); delta 9.18 (dd, J=6.0, 6.0 Hz, 1H), 8.05 (d, J=8.5 Hz, 2H), 8.00 (d, J=8.5 Hz, 2H), 7.26 - 7.18 (m, 5H), 5.81 (d, J=12.9 Hz, 1H), 4.43 (d, J=5.9 Hz, 2H), 3.93- 3.84 (m, 5H), 1.28 - 1.25 (m, 6H).

Reference： [1]Patent: WO2016/193241,2016,A1 .Location in patent: Page/Page column 112

35
3-chloro-5-trifluoromethylpyridine-2-carboxylic acid ethyl ester [ No CAS ]
[ 1201905-61-4 ]
C₁₃H₁₄F₃NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 80℃; for 1h;	A solution of ethyl 3-chloro-5-(trifluoromethyl)pyridine-2-carboxylate (700 mg, 2.76 mmol), 2- [(E)-2-ethoxyethenylj -4,4,5,5 -tetramethyl- 1 ,3,2-dioxaborolane (545 mg, 2.75 mmol),Pd(dppf)Cl (197 mg, 0.27 mmol ) and C52CO3 (2.7 g, 8.29 mmol) in 1,4-dioxane (15 mL)and water(5 mL) was stirred for 1 hour at 80 C. The reaction was then diluted by the addition of water. The resulting solution was extracted with EA. The crude product was purified byreverse phase C18 column chromatography to give the desired compound (550 mg, 69%) as off-white oil. ESI MS m/z = 290.1 [M+Hf.
69%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; at 80℃; for 1h;	A solution of ethyl 3-chloro-5-(trifluoromethyl)pyridine-2-carboxylate (700 mg, 2.76 mmol), <strong>[1201905-61-4]2-[(E)-2-ethoxyethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (545 mg, 2.75 mmol), Pd(dppf)Cl2 (197 mg, 0.27 mmol) and Cs2CO3 (2.7 g, 8.29 mmol) in 1,4-dioxane (15 mL) and water(5 mL) was stirred for 1 hour at 80 oC. The reaction was then diluted by the addition of water. The resulting solution was extracted with EA. The crude product was purified by reverse phase C18 column chromatography to give the desired compound (550 mg, 69%) as off-white oil. ESI MS m/z = 290.1 [M+H]+.

Reference： [1]Patent: WO2017/15449,2017,A1 .Location in patent: Page/Page column 344
[2]Patent: WO2019/67864,2019,A1 .Location in patent: Page/Page column 312

36
[ 1201905-61-4 ]
3-bromo-4-methyl-6-(trifluoromethyl)pyridin-2-amine [ No CAS ]
(E)-3-(2-ethoxyvinyl)-4-methyl-6-(trifluoromethyl)pyridin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With palladium diacetate; caesium carbonate; XPhos; In 1,4-dioxane; water; at 80℃; for 2h;Inert atmosphere;	A flask charged with 3-bromo-4-methyl-6-(trifluoromethyl)pyridin-2 -amine (38.3 g, 143 mmol), (E)- 2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (56.5 g, 285 mmol), diacetoxypalladium (0.960 g, 4.28 mmol), dicyclohexyl(2',4',6'-triisopropyl-[l,r-biphenyl]-2-yl)phosphine (XPhos) (4.28 g, 8.98 mmol) and cesium carbonate (116 g, 356 mmol) was degassed with N2 for 15 min before addition of 320 mL degassed dioxane/H20 (4:1). The mixture was heated at about 80 C for about 2 h. The mixture was cooled down to rt. The reaction mixture was partitioned between EtOAc and water and the aqueous layer was further extracted with EtOAc (2 x 50 mL). The organic layer was dried over Na2S04, filtered and concentrated to dryness. To the residue was added heptane and the resulting solid was collected by filtration and washed with heptane to give an off-white solid (1.45 g). The filtrate was concentrated to dryness again to give a thick black oil that was left at rt overnight. Significant solid formation was noticed and the solid was diluted with heptane, sonicated and filtered, washed with heptane to give a light brown solid (15.2 g, 42%). The filtrate was concentrated to dryness to give a black oil that was purified by flash chromatography (0-25% EtOAc/heptane over 30 min). The product containing fractions were concentrated to almost dryness. The solid was collected by filtration, washed with a small amount of heptane and dried to give the second crop of product as a light yellow solid (12.7 g, 35%). LC/MS (Method 1) Rt = 1.48 min.; MS m/z: 247 [M+H]+. NMR (400 MHz, DMSO-ita) delta 6.82 (s, 1H), 6.73 (d, J= 13.1 Hz, 1H), 6.12 (s, 2H), 5.45 (d, J= 13.1 Hz, 1H), 3.93 (q, J = 7.0 Hz, 2H), 2.23 (s, 3H), 1.25 (t, J= 7.0 Hz, 3H).

Reference： [1]Patent: WO2016/198908,2016,A1 .Location in patent: Page/Page column 359; 360

37
[ 1201905-61-4 ]
3-chloro-4-(hydroxymethyl)pyridine [ No CAS ]
C₁₀H₁₃NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In water; acetonitrile; at 120℃; for 2h;Inert atmosphere; Sealed tube; Microwave irradiation;	In a MW vial were successively added SPhos (74 mg, 6 mol %), Pd(OAc)2 (20 mg, 3 mol %), K3PO4 (1.59 g, 7.5 mmol), pyridine 33 (431 mg, 3.0 mmol), <strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (1.13 g, 5.7 mmol), CH3CN (12 mL) and water (8 mL). The MW vial was purged with N2 for 5 min then heated at 120 C for 2 h under MW conditions. The resulting mixture was filtered through a pad of Celite and the pad was washed several times with EtOAc. The filtrate was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by column chromatography using EtOAc (100%) as eluent to provide pyridine 34 (343 mg, 64%) as a colorless oil.

Reference： [1]Beilstein Journal of Organic Chemistry,2017,vol. 13,p. 988 - 994

38
[ 1201905-61-4 ]
C₁₂H₂₀ClNOSi [ No CAS ]
C₁₆H₂₇NO₂Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In water; acetonitrile; at 85℃; for 2h;Inert atmosphere; Sealed tube; Microwave irradiation;	In a MW vial were successively added SPhos (38 mg, 6 mol %), Pd(OAc)2 (10 mg, 3 mol %), K3PO4 (652 mg, 3.1 mmol), chloropyridine 37 (396 mg, 1.5 mmol), <strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (608 mg, 3.1 mmol), CH3CN (3.3 mL) and water (2.2 mL). The MW vial was purged with N2 for 5 min then heated at 85 C for 2 h under MW conditions. The resulting mixture was filtered through a pad of Celite and the pad was washed several times with EtOAc. The filtrate was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by column chromatography using gradient eluent (EtOAc-PE, 1:1 to 3:2) to lead to pyridine 38(343 mg, 76%) as a pale yellow oil.

Reference： [1]Beilstein Journal of Organic Chemistry,2017,vol. 13,p. 988 - 994

39
[ 1201905-61-4 ]
methyl 2-chloro-4-octyl-benzoate [ No CAS ]
methyl 2-(1-ethoxyvinyl)-4-octylbenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83.3%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; at 100℃; for 16h;	A mixture of methyl 2-chloro-4-octyl-benzoate (160.0 mg, 0.57 mmol), tricyclohexylphosphine (47.6 mg, 0.17 mmol), tris(dibenzylideneacetone)dipalladium(0) (51.8 mg, 0.06 mmol), (E)-1-ethoxyethene-2-boronic acid pinacol ester (123.3 mg, 0.62 mmol) and potassium phosphate tribasic (240.2 mg, 1.13 mmol) in 1,4-dioxane (4 mL) was stirred at 100C for 16 h and concentrated. The residue was taken up in EtOAc (20 mL), washed with water (20 mL x 2) and brine (20 mL), dried over Mg504 and concentrated. The crude was purified by flash column chromatography (20% ethyl acetate in petroleum ether, Rf = 0.7) to afford presumably methyl 2-(1-ethoxyvinyl)-4-octylbenzoate (150 mg, 83.3% yield) as a yellow oil, instead of expected regioisomer.

Reference： [1]Patent: WO2017/84630,2017,A1 .Location in patent: Paragraph 001064

40
[ 1201905-61-4 ]
[ 18643-86-2 ]
(E)-dimethyl 2-(2-ethoxyvinyl)terephthalate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In tetrahydrofuran; 1,4-dioxane; water; at 80℃;Inert atmosphere;	To a solution of dimethyl 2-bromoterephthalate A1 (723 mg, 2.65 mmol) in THF was added water (3 mL), dioxane (6 mL), K2C03 (1 .1 g, 7.95 mmol), (£)-2-(2-ethoxyvinyl)-4,4,5,5- tetramethyl-1 ,3,2-dioxaborolane (630 mg, 3.18 mmol) and PdCI2(dppf) (194 mg, 0.27 mmol). The mixture was heated at 80 C under N2 overnight, then the reaction was filtered and the filtrate concentrated under reduced pressure. The residue obtained was partitioned between EtOAc (15 mL) and water (10 mL) and the aqueous layer was extracted with EtOAc (3x8 mL). The combined organic fractions were washed with saturated aqueous NaHCC>3 (10 mL) and brine (10 mL), dried (Na2S04), filtered and concentrated. The residue was purified by column chromatography (1 % EtOAc/petroleum ether) to give the title compound as a white solid (520 mg, 74%). LCMS: RT 2.84 min; m/z 265.1 [M+H] +

Reference： [1]Patent: WO2017/153515,2017,A1 .Location in patent: Page/Page column 67

41
[ 1201905-61-4 ]
2-chloro-5-fluoro-3-iodopyridin-4-amine [ No CAS ]
(E)-2-chloro-3-(2-ethoxyvinyl)-5-fluoropyridin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.4 g	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In water; acetonitrile; at 110℃; for 16h;Inert atmosphere;	A stirred solution of 2-chloro-5-fluoro-3-iodopyridin-4-amine (2 g, 7.34 mmol, (0824) 1 equiv), (E)-2-(2-ethoxyvinyl)-4, 4, 5, 5-tetramethyl-1 ,3,2-dioxaborolane (2.91 g, 14.62 mmol, (0825) 2 equiv), Potassium phosphate (3.1 g, 14. 62 mmol, 2 equiv) in acetonitrile : water (3:2, 30ml : 20ml) was degassed with N2 for 10 minutes. Palladium acetate (49. 4 mg, 0.22 mmol, 0.03 equiv) and 'S' phos (226 mg, 0.55 mmol, 0.075 equiv) were added and the reaction mixture was stirred for 16h at 1 10C. After consumption of the starting material, the reaction mixture was cooled to room temperature and filtered through celite bed and washed with EtOAc (100 ml_). The filtrate was washed with water, brine solution and concentrated to give the crude product. The crude product was purified by silica gel flash column chromatography. The compound eluted out in 60% EtOAc : Hexane. The pure fractions were evaporated to obtain (E)-2-chloro-3-(2-ethoxyvinyl)-5-fluoropyridin-4-amine as pale yellow solid (1 .4 g, 88%). LCMS (ES) m/z = 217.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) delta ppm 1 .25 (t, J = 6.8 Hz, 3H), 3.94 (q, J = 6.8 Hz, 2H), 5.42 (d, J = 13.2 Hz, 1 H), 6.23 (s, 2H), 6.82 (d, J = 12.8 Hz, 1 H), 7.80 (d, J = 2.4 Hz, 1 H).

Reference： [1]Patent: WO2018/15879,2018,A1 .Location in patent: Page/Page column 120-121

42
[ 1201905-61-4 ]
methyl 2-benzyl-5-bromo-1-(4-methoxybenzyl)-1H-imidazole-4-carboxylate [ No CAS ]
(E)-methyl 2-benzyl-5-(2-ethoxyvinyl)-1-(4-methoxybenzyl)-1H-imidazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.22 g	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,2-dimethoxyethane; water; at 90℃;Inert atmosphere;	C) (E)-methyl 2-benzyl-5-(2-ethoxyvinyl)-1-(4-methoxybenzyl)-1H-imidazole-4-carboxylate A mixture of methyl 2-benzyl-5-bromo-1-(4-methoxybenzyl)-1H-imidazole-4-carboxylate (0.30 g), <strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (0.286 g), cesium carbonate (0.518 g), 1,1'-bis(diphenylphosphino)ferrocene dichloropalladium(II) dichloromethane complex (0.059 g), 1,2-dimethoxyethane (8 mL) and water (1 mL) was stirred overnight under argon atmosphere at 90C. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.22 g). MS: [M+H]+ 407.3.

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 2384 - 2409
[2]Patent: EP3366684,2018,A1 .Location in patent: Paragraph 0498

43
[ 1201905-61-4 ]
ethyl 1-benzyl-4-bromo-1H-pyrazole-3-carboxylate [ No CAS ]
(E)-ethyl 1-benzyl-4-(2-ethoxyvinyl)-1H-pyrazole-3-carboxylate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 2384 - 2409

44
[ 1201905-61-4 ]
ethyl 4-bromo-1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate [ No CAS ]
ethyl 4-(2-ethoxyvinyl)-1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 2384 - 2409

45
[ 1201905-61-4 ]
(+/-)-(3aR,4S,6R,6aS)-6-((5-bromo-6-methylpyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-4H-cyclopenta[d][1,3]dioxol-4-ol [ No CAS ]
(+/-)-(3aR,4S,6R,6aS)-6-((5-((E)-2-ethoxyvinyl)-6-methylpyrimidin-4-yl)amino)-2,2-dimethyltetrahydro-4H-cyclopenta[d][1,3]dioxol-4-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; sodium carbonate; In 1,4-dioxane; at 80℃; for 23h;Inert atmosphere;	Vacuum-washing T-2 in dioxane (19.9 ml, 0.3 M) with nitrogen(2.06 g, 5.98 mmol) and<strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (1.19 g, 5.98 mmol)The solution, then add 2 N sodium carbonate (aq) (8.98 ml),S-Phos pre-catalyst (136 mg, 0.180 mmol) was then added.The resulting mixture was heated to 80 C for 23 hours.The reaction mixture was cooled to room temperature and then diluted with EtOAc and water.The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to an oil.Then 0% to 100% EtOAc in heptane by tannin gel chromatographyThe gradient elution was purified to give T-3 as a white solid, 1.21 g (60% yield).

Reference： [1]Patent: TW2018/2074,2018,A .Location in patent: Page/Page column 150; 151

46
[ 1201905-61-4 ]
ethyl 3-bromo-5-chloro-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate [ No CAS ]
ethyl (E)-5-chloro-3-(2-ethoxyvinyl)-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 6h;	Compound M (1.5 g, 4.48 mmol, 1 eq.), (E)-1-ethoxyethene-2-boronic acid pinacol ester (1.05 mL, 4.9 mmol, 1.1 eq.), Pd2(dppf)2C12 CHCl (164 mg, 0.22 mmol, 0.05 eq.), cesium carbonate (4.4 g, 13.45 mmol, 3 eq.), water (2 mL) and 1,4-dioxane (20 mL) were added to a vial (40 mL). After bubbling nitrogen through the solution for 5 minutes, the vial was capped and heated to 90C for 6 hours. The reaction was filtered over a pad of Celite, washed with DCMIEtOAc (3x) and concentrated. The crude product was purified by flash chromatography on silica gel using 0-70% ethyl acetate/hexanes to provide the title compound (1.2g, 82% yield). ES-MS [M+lfb: 326.3.

Reference： [1]Patent: WO2018/85813,2018,A1 .Location in patent: Paragraph 00245

47
[ 1201905-61-4 ]
ethyl 5-bromo-3-chloro-4-methylthieno[2,3-c]pyridazine-6-carboxylate [ No CAS ]
ethyl (E)-3-chloro-5-(2-ethoxyvinyl)-4-methylthieno[2,3-c]pyridazine-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 2h;Inert atmosphere;	Compound U (0.26 g, 0.77 mmol, 1 eq.), (E)-1-ethoxyethene-2-boronic acid pinacol ester (0.23 g, 1.16 mmol, 1.5 eq.), Pd2(dppf)2C12 (28 mg, 0.04 mmol, 0.05 eq.), cesium carbonate (0.76 g, 2.32 mmol, 3 eq.), water (0.8 mL) and 1,4-dioxane (3 mL) were added to a vial (20 mL). After bubbling nitrogen through the solution for 5 minutes, the vial was capped and heated to 90C for 2 hours. The reaction was filtered over a pad of Celite, washed with EtOAc (3x) and washed with H20 and brine. After the organic layer was dried (Na2SO4), solvent was removed under vacuo to afford desired product. The material was taken through without further purification. ES-MS [M+lfb: 327.3.

Reference： [1]Patent: WO2018/85813,2018,A1 .Location in patent: Paragraph 00255

48
[ 1201905-61-4 ]
methyl 5-bromo-3-(difluoromethyl)-4-methylthieno[2,3-c]pyridazine-6-carboxylate [ No CAS ]
C₁₁H₆F₂N₂O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Compound AA (32 mg, 0.09 mmol), (E)-1-ethoxyethene-2-boronic acid pinacol ester (23 mg, 0.11 mmol) [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium (3 mg, 0.005 mmol) cesium carbonate (78 mg, 0.24 mmol) in 1,4-Dioxane (0.5mL) and Water (0. lmL) was stirred at 90C for 1 hr. The mixture was diluted with EtOAc, washed with H20 and brine, dried over Na2504 then concentrated. To the residue was added trifluoroacetic acid (1 mL) and the mixture microwaved at 125 C for 1 hr. The solution was concentrated to provide compound BB, which was used without further purification. To compound BB was added ammonium hydroxide (1.5mL) was added and the mixture stirred at 100C for 1 hr. The mixture was concentrated then dried in vacuo. Phosphorus oxychloride (1.mL, 10.7mmol) was added to the residue and the mixture stirred at 100C for 1 hr. The solution was concentrated and the residue dissolved in EtOAc, washed with sat. NaHCO3 (aq) and brine, dried over Na2SO4 then concentrated to give the title compound (26 mg, 95% yield) as a dark brown solid. ES-MS [M+lfb: 285.8.

Reference： [1]Patent: WO2018/85813,2018,A1 .Location in patent: Paragraph 00265

49
[ 1201905-61-4 ]
[ 1458-01-1 ]
methyl 3,5-diamino-6-[(E)-2-ethoxyethenyl]pyrazine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In water; acetonitrile; at 80℃; for 2h;	A mixture of methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (40.0 g, 197 mmol), 2- [(E)-2-ethoxyethenyl]-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (84 ml, 400 mmol), SPhos (8.11 g, 19.7 mmol), palladium(ll) acetate (2.22 g, 9.87 mmol) and K3P04 (83.8 g, 395 mmol) in water:MeCN (2:3, 350 ml) was stirred at 80 °C for 2 h then allowed to cool to RT. The solid was collected by filtration then washed with EtOAc (100 ml) and water (100 ml) then dried in vacuo to afford the product as a brown solid (36.7 g, 76percent). 1 H NMR (500 MHz, DMSO-cfe) delta 7.15 (d, J = 12.2 Hz, 1 H), 6.79 (s, 4H), 5.97 (d, J = 12.2 Hz, 1 H), 3.91 (q, J = 7.0 Hz, 2H), 3.72 (s, 3H), 1.25 (t, J = 7.0 Hz, 3H). LC/MS (System A): m/z (ESI+) = 239 [MH+], Rt = 0.88 min, UV purity = 98percent.

Reference： [1]Patent: WO2018/96325,2018,A1 .Location in patent: Page/Page column 61-62

50
[ 1201905-61-4 ]
N-(5-bromo-3,6-difluoropyridin-2-yl)-6-chloro-1H-indole-3-sulfonamide [ No CAS ]
6-chloro-N-{5-[(E)-2-ethoxyethenyl]-3,6-difluoropyridin-2-yl}-1H-indole-3-sulfonamide [ 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 120℃; for 0.333333h;Inert atmosphere; Microwave irradiation;	A mixture of N-(5-bromo-3,6-difluoropyridin-2-yl)-6-chloro-i H-indole-3-sulfonamide 1-245 (100 mg, 0.24 mmol), (E)-i-ethoxyethene-2-boronic acid pinacol ester (58mg, 0.28 mmol), [1,1 ?-bis(diphenylphosphino)ferrocene]dichloropalladium (19 mg, 0.O24mmol) and potassium carbonate (99 mg, 0.71 mmol) was dissolved in dioxane : water (3:1, 2 mL) and flushed with argon via a septum. Subsequently, the reaction mixture was stirred at 120 Cfor 20 mm in a microwave. The mixture was diluted with water and extracted twice with ethyl acetate. The combined organic layers were dried over Mg504 and concentrated by rotary evaporation. The crude mixture was purified by preparative HPLC (Basic prep LCMS Method 1). It afforded 25 mg of 6-chloro-N-{5-[(E)-2-ethoxyethenyl]-3,6- difluoropyridin-2-yl}-i H-indole-3-sulfonamide 1-332 as a beige solid.Yield: 26%.Basic LCMS Method 1 (ES-): 412 (M-H)-, 94% purity.

Reference： [1]Patent: WO2018/122232,2018,A1 .Location in patent: Page/Page column 421

51
[ 1201905-61-4 ]
(S)-tert-butyl (4-((1-(5-bromo-2-fluorophenyl)ethyl)amino)-5-chloro-2-fluorophenyl)sulfonyl(thiazol-4-yl)carbamate [ No CAS ]
tert-butyl (S,E)-((5-chloro-4-((1-(5-(2-ethoxyvinyl)-2-fluorophenyl)ethyl)amino)-2-fluorophenyl)sulfonyl)(thiazol-4-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 90℃; for 12h;	To a solution of (S)-tert-butyl (4-((1-(5-bromo-2-fluorophenyl)ethyl)amino)-5-chloro-2-fluorophenyl)sulfonyl(thiazol-4-yl)carbamate (1.00 g, 1.64 mmol), <strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (0.65 g, 3.3 mmol) and sodium carbonate (0.35 g, 3.3 mmol) in toluene (5 mL), ethanol (5 mL) and water (5 mL) was added tetrakis(triphenylphosphine)-palladium(0) (0.38 g, 0.33 mmol). The reaction mixture was heated 90 C. for 12 h. After cooling to ambient temperature, the reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine (20 mL), dried over anhydrous sodium sulfate, and filtered. Concentration of the filtrate in vacuo and purification of the residue by silica gel chromatography, eluting with a gradient of 10 to 33% of ethyl acetate in petroleum ether, afforded the title compound as a colorless oil (0.90 g, 91% yield): 1H NMR (400 MHz, CDCl3) delta8.77 (d, J=2.0 Hz, 1H), 7.96 (d, J=7.2 Hz, 1H), 7.47 (d, J=2.0 Hz, 1H), 7.14-7.09 (m, 1H), 7.04-6.97 (m, 2H), 6.86 (d, J=12.8 Hz, 1H), 6.21 (d, J=12.0 Hz, 1H), 5.74 (d, J=12.8 Hz, 1H), 4.81 (t, J=6.4 Hz, 1H), 3.87 (q, J=7.2 Hz, 3H), 1.65 (d, J=6.4 Hz, 3H), 1.34 (s, 9H), 1.33-1.30 (m, 3H); MS (ES+) m/z 499.9 (M-99).

Reference： [1]Patent: US2018/162868,2018,A1 .Location in patent: Paragraph 1527-1528

52
[ 1201905-61-4 ]
N-(5-(4-bromo-5-chloro-2-(difluoromethoxy)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide [ No CAS ]
N-[5-[5-chloro-2-(difluoromethoxy)-4-[(E)-2-ethoxyethenyl]phenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 80℃;	A degassed mixture of N-[5-[4-bromo-5-chloro-2-(difluoromethoxy)phenyl]-l-[[2- (trimethylsilyl)ethoxy]methyl]- lH-pyrazol-4-yl]pyrazolo[ 1 ,5 -a]pyrimidine-3 -carboxamide (Intermediate 18) (300 mg, 0.489 mmol), 2-[(E)-2-ethoxyethenyl]-4,4,5,5-tetramethyl-l,3,2- dioxaborolane (194 mg, 0.979 mmol), Pd(dppf)Cl2.CH2Cl2 (40.0 mg, 0.0490 mmol) and Cs2C03 (320 mg, 0.982 mmol) in dioxane (10 mL) and water (2.0 mL) was stirred at 80 C overnight. The resulting mixture was allowed to cool to RT and concentrated under vacuum. The residue was purified by silica gel chromatography eluting with ethyl acetate/petroleum ether (55/45) to give N-[5-[5-chloro-2-(difluoromethoxy)-4-[(E)-2-ethoxyethenyl]phenyl]-l- [[2-(trimethylsilyl)ethoxy]methyl]- lH-pyrazol-4-yl]pyrazolo[ 1 ,5-a]pyrimidine-3- carboxamide (340 mg, 75%) as a yellow solid. LC/MS (Method D, ESI): [M+H]+ = 605, RT = 1.55 min.

Reference： [1]Patent: WO2018/122212,2018,A1 .Location in patent: Page/Page column 177

53
[ 1201905-61-4 ]
(R)-8-bromo-N2-(3-chloro-4-fluorophenyl)-N4-(1-cyclopropylethyl)quinazoline-2,4-diamine [ No CAS ]
(R,E)-N2-(3-chloro-4-fluorophenyl)-N4-(1-cyclopropylethyl)-8-(2-ethoxyvinyl)quinazoline-2,4-diamine [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2018,vol. 9,p. 941 - 946

54
[ 1201905-61-4 ]
[ 1214328-96-7 ]
methyl 6-chloro-3-((E)-2-ethoxyvinyl)pyridine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
560 mg	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In water; acetonitrile; at 60℃; for 2.0h;Inert atmosphere;	B) methyl 6-chloro-3-((E)-2-ethoxyvinyl)pyridine-2-carboxylate To a mixture of <strong>[1214328-96-7]methyl 3-bromo-6-chloropyridine-2-carboxylate</strong> (2.00 g) in acetonitrile (30 mL) and water (20 mL) were added 2-((E)-2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.42 g), tripotassium phosphate (3.39 g), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (328 mg) and palladium(II) acetate (90 mg), and the mixture was stirred under nitrogen atmosphere at 60C for 2 hr. The reaction mixture was cooled to room temperature, and diluted with ethyl acetate, and the insoluble substance was removed by filtration. The filtrate was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether) to give the title compound (560 mg). 1H NMR (400 MHz, DMSO-d6) delta 1.28 (3H, t, J = 7.6 Hz), 3.88 (3H, s), 3.90-4.00 (2H, m), 6.27 (1H, d, J = 12.8 Hz), 7.43 (1H, d, J = 12.8 Hz), 7.60 (1H, d, J = 8.8 Hz), 8.16 (1H, d, J = 8.8 Hz) .

Reference： [1]Patent: EP3366684,2018,A1 .Location in patent: Paragraph 0437

55
[ 1201905-61-4 ]
ethyl 1-benzyl-4-bromo-5-methoxy-1H-pyrazole-3-carboxylate [ No CAS ]
(E)-ethyl 1-benzyl-4-(2-ethoxyvinyl)-5-methoxy-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
124 mg	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,2-dimethoxyethane; water; at 90℃;Inert atmosphere;	C) (E)-ethyl 1-benzyl-4-(2-ethoxyvinyl)-5-methoxy-1H-pyrazole-3-carboxylate A mixture of ethyl 1-benzyl-4-bromo-5-methoxy-1H-pyrazole-3-carboxylate (239.5 mg), <strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (210 mg), 1,1'-bis(diphenylphosphino)ferrocene dichloropalladium(II) (51.7 mg), cesium carbonate (690 mg), 1,2-dimethoxyethane (9 mL) and water (1 mL) was stirred overnight under nitrogen atmosphere at 90C. To the reaction solution was added saturated brine, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (124 mg). MS: [M+H]+ 331.3.

Reference： [1]Patent: EP3366684,2018,A1 .Location in patent: Paragraph 0483

56
[ 1201905-61-4 ]
diethyl 1-benzyl-4-iodo-1H-pyrazole-3,5-dicarboxylate [ No CAS ]
(E)-diethyl 1-benzyl-4-(2-ethoxyvinyl)-1H-pyrazole-3,5-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.771 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,2-dimethoxyethane; water; at 90℃;Inert atmosphere;	B) (E)-diethyl 1-benzyl-4-(2-ethoxyvinyl)-1H-pyrazole-3,5-dicarboxylate A mixture of diethyl 1-benzyl-4-iodo-1H-pyrazole-3,5-dicarboxylate (1.0 g), <strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (0.833 g), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.171 g), cesium carbonate (1.674 g), water (1 mL) and 1,2-dimethoxyethane (11 mL) was stirred overnight under argon atmosphere at 90C. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.771 g). MS: [M+H]+ 373.3.

Reference： [1]Patent: EP3366684,2018,A1 .Location in patent: Paragraph 0490

57
[ 1201905-61-4 ]
C₆H₆BrIN₂ [ No CAS ]
C₁₀H₁₃BrN₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; lithium hydroxide; In dichloromethane; N,N-dimethyl-formamide; at 20 - 70℃; for 18h;Inert atmosphere;	To a mixture of intermediate 150 (600 mg, 1.92 mmol) and trans-2-ethoxyvinylboronic acid pinacol ester (493.7 mg, 2.49 mmol) in DMF (5 mL) at rt and under N2 atmosphere, lithium hydroxide (137.7 mg, 5.75 mmol) and [Iota, - bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (CAS: 95464-05-4; 31.66 mg, 0.038 mmol) were added. The mixture was heated at 70 C for 18 h. After cooling to rt water and EtOAc were added. The organic layer was separated and the volatiles were evaporated in vacuo. The residue thus obtained was purified by flash chromatography (Si02, EtOAc in heptane, 0/100 to 10/90). The desired fractions were evaporated in vacio to yield intermediate 149 (430 mg, 87%) as an oil.

Reference： [1]Patent: WO2018/154133,2018,A1 .Location in patent: Page/Page column 96; 97

58
[ 1201905-61-4 ]
(3S)-3-[(1R)-1-(4-bromophenyl)ethyl]-3-methyl-1-tritylpyrrolidine-2,5-dione [ No CAS ]
(3S)-3-[(1R)-1-[4-[(E)-2-ethoxyvinyl]phenyl]ethyl]-3-methyl-1-tritylpyrrolidine-2,5-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91.6%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; water; caesium carbonate; In 1,4-dioxane; for 0.5h;Inert atmosphere; Reflux;	Scheme 2, step B: (3S)-3-[(lR)-l-(4-bromophenyl)ethyl]-3-methyl-l-trityl- pyrrolidine-2,5-dione (43.5 g, 80.8 mmol), 2-[(£)-2-ethoxyvinyl]-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (17.6 g, 88.8 mmol), Cs2C03 (80.0 g, 245.5 mmol)l,4-dioxane (450 mL) and water (90 mL) are added to a 3-necked 2L flask, with mechanical stirring, under nitrogen. The reaction mixture is purged with nitrogen/vacuum, 1, 1'- bis(diphenylphosphino)ferrocene-palladium(II)dichloride-DCM complex (1.7 g, 2.0 mmol) is added, and the reaction mixture is heated to reflux for about 30 min. The reaction mixture is cooled to RT, poured into 500 mL water / 500 mL MTBE, and the resulting layers are separated. The organic layer is dried over Na2S04, filtered, concentrated under reduced pressure, and the resulting residue is reconstituted in DCM (250 mL) and again evaporated under reduced pressure. The resulting residue is transferred to a 3-necked round bottom flask, MeOH (750 mL) is added, and the mixture is heated to a gentle reflux. Water (250 mL) is added dropwise over 15 min, and the mixture is cooled to RT. The resulting solids are collected by filtration, washed with 3 : 1 MeOH/water (100 mL), and dried under a stream of nitrogen to obtain the title compound (39.2 g, 91.6% yield) as a light green solid. ES/MS (m/z): 530.2 (M+H).

Reference： [1]Patent: WO2018/213056,2018,A1 .Location in patent: Page/Page column 32-33

59
[ 1201905-61-4 ]
methyl (2S,3S)-3-[(5-bromo-2-chloro-pyrimidin-4-yl)amino]bicyclo[2.2.2]octane-2-carboxylate [ No CAS ]
methyl (2S,3S)-3-[[2-chloro-5-[(E)-2-ethoxyvinyl]pyrimidin-4-yl]amino]bicyclo[2.2.2]octane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51.2%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; at 80℃; for 2h;Inert atmosphere;	The a solution of compound 2 (60.00mg, 160.15 mumol, 1.00 eq) and <strong>[1201905-61-4]2-[(E)-2-ethoxyvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (34.89mg, 176.17 mumol, 1.10 eq) in dioxane (2.00mL) was added Pd(dppf)Cl2 (11.72mg, 16.02 mumol, 0.10 eq) and K2CO3 (44.27mg, 320.30 mumol, 2.00 eq) under N2, the mixture was heated to 80C for 2h. The mixture was concentrated under reduced pressure and the residue was purified by Prep-TLC with PE: EtOAc(2:1) to afford compound 3 (30.00mg, 82.00 mumol, 51.20% yield) as colorless oil. 1HNMR (400MHz, CHLOROFORM-d) delta: 7.80 (s, 1H), 6.68 (d, J=12.4Hz, 1H), 5.34 (d, J=12.8Hz, 1H), 4.99-5.01 (m, 1H), 4.40 (br s, 1H),3.93 (q, J=7.0Hz,2H), 3.77 (s, 3H), 2.34-2.36 (m, 1H), 1.83-1.95 (m, 1H), 1.54-1.68 (m, 8H), 1.36 (t, J=7.0Hz,3H). MS (ESI) m/z calc. for C18H24ClN3O3: [M+H]+: 366.2; found: 366.0.

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 162,p. 249 - 265

60
[ 1201905-61-4 ]
tert-butyl 7-(benzyloxy)-1-chloro-8-methoxy-5H-pyrido[4,3-b]indole-5-carboxylate [ No CAS ]
tert-butyl 7-(benzyloxy)-1-[(E)-2-ethoxyethenyl]-8-methoxy-5H-pyrido[4,3-b]indole-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In water; toluene; for 4h;Inert atmosphere;	A mixture of tert-butyl 7-(benzyloxy)- 1 -chloro-8-methoxy-5H-pyrido[4,3-b]indole-5- carboxylate (450.00 mg; 1.03 mmol; 1.00 eq.), <strong>[1201905-61-4]2-[(E)-2-ethoxyethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (365.53 mg; 1.85 mmol; 1.80 eq.), Pd(dppf)2C12.DCM (83.73 mg; 0.10 mmol; 0.10 eq.) and Cesium carbonate (1 336.23 mg; 4.10 mmol; 4.00 eq.) in toluene (12 mL) and water (1 mL) was spurge with nitrogen for 10 minutes. The resulting mixture was allowed to reflux under N2 atmosphere for 4 h. The reaction mixture was allowed to cool to rt, diluted with water and extracted with EtOAc thrice. The combined organic solution was concentrated under reduced pressure. Theresidue was purified by flash chromatography on 25 g silica gel column eluted with 0-60% EtOAc inhexanes to provide tert-butyl 7-(benzyloxy)- 1- [(E)-2-ethoxyethenyl] -8-methoxy-5H-pyrido[4,3 -b]indole-5-carboxylate as a white solid (393mg, 8 1%).

Reference： [1]Patent: WO2018/226998,2018,A1 .Location in patent: Page/Page column 127

61
[ 304902-96-3 ]
[ 1201905-61-4 ]
2-cyclopropyl-5-[(E)-2-ethoxyvinyl]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85.8%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 90℃; for 18h;Inert atmosphere;	Water (1 mL) is added under N2 to a solution of 5-bromo-2-cyclopropyl- pyrimidine (200 mg, 0.954 mmol), 2-[(E)-2-ethoxyvinyl]-4,4,5, 5-tetramethyl- 1,3,2- dioxaborolane (219mg, 1.05 mmol), 1,1 ?-bi s(diphenylphosphino)ferrocene10 palladium(II)dichloride dichloromethane complex (3 9.8mg, 0.0477 mmol) and K2C03(395.8mg, 2.86 mmol) in 1,4-dioxane (4 mL) at room temperature. The mixture is stirred at 90 C under N2 for 18 hours. The mixture is diluted with DCM, dried over Na2504, filtered, and concentrated to dryness. The residue is purified by silica gel flash chromatography with 13% EtOAc in hexanes to give the title compound (164 mg, 85.8%)as a colorless oil. ES/MS (m/z): 191 (M+1).

Reference： [1]Patent: WO2019/50794,2019,A1 .Location in patent: Page/Page column 14

62
[ 1201905-61-4 ]
C₂₃H₁₇BrFN₅O [ No CAS ]
C₂₇H₂₄FN₅O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 3122 - 3134

63
[ 1201905-61-4 ]
C₂₄H₁₇BrF₃N₅O [ No CAS ]
C₂₈H₂₄F₃N₅O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 3122 - 3134

64
[ 1201905-61-4 ]
C₂₄H₁₇BrF₃N₅O [ No CAS ]
C₂₈H₂₄F₃N₅O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 3122 - 3134

65
[ 61441-09-6 ]
[ 1201905-61-4 ]
C₁₃H₁₄O₅ [ No CAS ]

Reference： [1]Tetrahedron Letters,2019,vol. 60,p. 1259 - 1261

66
[ 1201905-61-4 ]
ethyl 5-bromo-2,4-dimethylthieno[2,3-d]pyrimidine-6-carboxylate [ No CAS ]
ethyl 5-[(E)-2-ethoxyvinyl]-2,4-dimethylthieno[2,3-d]pyrimidine-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;	A mixture of 44 ethyl 5-bromo-2,4-dimethylthieno[2,3-d]pyrimidine-6-carboxylate (compound ix, 855 mg, 2.71 mmol, 1.0 eq.), 46 (E)-1-ethoxyethene-2-boronic acid pinacol ester (806 mg, 4.07 mmol, 1.5 eq.), 47 [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium (199 mg, 0.27 mmol, 0.10 eq.), 48 cesium carbonate (2.65 g, 8.14 mmol, 3.0 eq.) in 49 1,4-dioxane (16.3 mL, 0.15 M) and 50 water (1.6 mL) was stirred at 100 C. After 1 hour, the mixture was diluted with EtOAc, washed with H2O and brine, dried over Na2SO4, filtered and concentrated. The crude material was purified using flash column chromatography on silica gel (0-50% EtOAc/DCM) to provide the 51 title compound as a pale yellow solid (630 mg, 76%). 1H NMR (400 MHz, CDC3) delta 6.71 (d, J=13.0 Hz, 1H), 6.18 (d, J=13.0 Hz, 1H), 4.37 (q, J=7.1 Hz, 2H), 4.02 (q, J=7.0 Hz, 2H), 2.85 (s, 3H), 2.78 (s, 3H), 1.40 (t, J=7.1 Hz, 3H), 1.39 (t, J=7.1 Hz, 3H); ES-MS [M+1]+: 307.2.

Reference： [1]Patent: US2019/167688,2019,A1 .Location in patent: Paragraph 0457; 0460

67
[ 1201905-61-4 ]
2-(3-(8-amino-6-bromoimidazo[1,2-a]pyrazin-3-yl)-4-methylphenyl)-1,1,1-trifluoropropan-2-ol [ No CAS ]
(E)-2-(3-(8-amino-6-(2-ethoxyvinyl)imidazo[1,2-a]pyrazin-3-yl)-4-methylphenyl)-1,1,1-trifluoropropan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In tetrahydrofuran; water; at 80℃; for 12h;Inert atmosphere;	A solution of 2-(3-(8-amino-6-bromoimidazo[l,2-a]pyrazin-3-yl)-4-methylphenyl)- l,l,l-trifluoropropan-2-ol (400 mg, 0.96 mmol, ematiomer 2) and (£)-2-(2-ethoxyvinyl)- 4,4,5, 5-tetramethyl-l,3,2-dioxaborolane (477 mg, 2.41 mmol) in THF (12 mL) was treated with 1 M aqueous potassium carbonate (2.5 mL) and dichloro[l,l'- bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (157 mg, 0.19 mmol). The reaction mixture was degassed with nitrogen for 5 min, and stirred at 80 C for 12 h. The resulting mixture was diluted with MeOH and passed through a Celite pad and concentrated. Purification via flash column chromatography using ethyl acetate in hexanes (0% to 100%) gave the desired product (250 mg, 0.61 mmol, 64%) as yellow oil. LCMS for C20H22F3N4O2 (M+H)+: m/z = 407.2; Found: 407.2.

Reference： [1]Patent: WO2019/79469,2019,A1 .Location in patent: Page/Page column 263-264

68
[ 1201905-61-4 ]
6-bromo-2-iodo-5-methylpyridin-3-amine [ No CAS ]
(E)-6-bromo-2-(2-ethoxyvinyl)-5-methylpyridin-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53.2%	With tetrakis(triphenylphosphine) palladium(0); sodium hydroxide; In tetrahydrofuran; at 80℃; for 16h;Inert atmosphere;	To a solution of 6-bromo-2-iodo-5-methylpyridin-3-amine (16 g, 51.1 mmol), and <strong>[1201905-61-4](E)-<strong>[1201905-61-4]2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong></strong> (15.19 g, 77 mmol) in THF (350 mL) was added sodium hydroxide (6.14 g, 153 mmol). The mixture was degassed for 10 min with nitrogen, tetrakis(triphenylphosphine)palladium (1.182 g, 1.023 mmol) was added, and the mixture was further degassed for 5 min. The resulting mixture was stirred at 80 C. for 16 h. The reaction mass was filtered through Celite, extracted with EtOAc (100 mL) and washed with water (2*100 mL), dried over sodium sulfate, filtered and concentrated to get crude compound. The crude compound was purified by combiflash using 120 g silica column, compound was eluted with 22% EtOAc in petroleum ether, the fractions were collected, concentrated to afford (E)-6-bromo-2-(2-ethoxyvinyl)-5-methylpyridin-3-amine (7 g, 27.2 mmol, 53.2% yield) as a brown solid. LCMS retention time 2.41 min [D]. MS m/z: 259.1 (M+2H).

Reference： [1]Patent: US2019/185469,2019,A1 .Location in patent: Paragraph 0538-0539

69
[ 49844-93-1 ]
[ 1201905-61-4 ]
2-[(E)-2-ethoxyvinyl]-4-methylsulfanyl-pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; for 4h;Inert atmosphere; Reflux;	To a suspension of 2-chloro-4-(methylthio)pyrimidine (56.1 g, 349.3 mmol) and 2 M aq. Na2CO3 (524 mL, 1.05 mol) in 1,2-dimethoxyethane (730 mL) was added 2-[(E)-2- ethoxyvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (76.1 g, 384 mmol). Pd(PPh3)4 (20.2 g, 17.5 mmol) was added and the mixture degassed. The reaction was placed under a nitrogen atmosphere and heated at reflux for 4 hours. The mixture was cooled to ambient temperature and partitioned between EtOAc (1.1 L) and water (560 mL). The organic layer was washed with water (2 x 560 mL), the combined organic layers were re-extracted with EtOAc (280 mL) and the combined organic phases were washed with brine (x 1), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica, eluting with 0 to 25% EtOAc/petroleum ether) to give (E)-2-(2-ethoxyvinyl)-4-(methylthio)pyrimidine as a pale yellow, crystalline solid (62.4 g, 91%); 1H NMR (500 MHz, Chloroform-d) delta 8.18 (d, J = 5.5 Hz, 1H), 7.95 (d, J = 12.6 Hz, 1H), 6.85 (d, J = 5.5 Hz, 1H), 5.91 (d, J = 12.6 Hz, 1H), 4.02 (q, J = 7.0 Hz, 2H), 2.56 (s, 3H), 1.40 (t, J = 7.0 Hz, 3H); ES+ [M+H]= 197.1.
90%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; for 2h;Inert atmosphere; Reflux;	A solution of 2-chloro-4-methylsulfanyl-pyrimidine (1 g, 6.23 mmol), Na2CO3 (9.3 mL of 2 M aq., 18.60 mmol) and <strong>[1201905-61-4]2-[(E)-2-ethoxyvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (1.35 g, 6.82 mmol) in 1,2-dimethoxyethane (15 mL) was degassed with nitrogen. Pd(PPh3)4 (600 mg, 0.519 mmol) was added and the mixture again degassed with nitrogen. The mixture was heated under reflux for 2 hours. The reaction mixture was cooled to ambient temperature, partitioned between EtOAc and water and the layers separated. The aqueous layer was extracted with EtOAc and the combined organic extracts washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica, EtOAc/petrol gradient) to afford 2-[(E)-2-ethoxyvinyl]-4-methylsulfanyl-pyrimidine (1.10 g, 90%); 1H NMR (500 MHz, Chloroform-d) delta 8.19 (d, 1H), 7.94 (d, 1H), 6.85 (d, 1H), 5.90 (d, 1H), 4.02 (q, 2H), 2.56 (s, 3H), 1.40 (t, 3H); MS m/z 197.1 (M+H).

Reference： [1]Patent: WO2019/148136,2019,A1 .Location in patent: Paragraph 00412
[2]Patent: WO2019/148132,2019,A1 .Location in patent: Paragraph 00916; 00917

70
[ 1201905-61-4 ]
[ 89283-48-7 ]
4-[(E)-2-ethoxyvinyl]-6-methylsulfanyl-pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; for 2h;Inert atmosphere; Reflux;	To a suspension of <strong>[89283-48-7]4-chloro-6-methylsulfanyl-pyrimidine</strong> (30 g, 186.8 mmol) and Na2CO3 (280.2 mL of 2 M, 560.4 mmol) in 1,2-dimethoxyethane (400 mL) was added 2-[(E)-2- ethoxyvinyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (37.7 g, 190.3 mmol). The mixture was then degassed via vacuum/nitrogen cycles (x 3), then Pd(PPh3)4 (12.95 g, 11.21 mmol) was added and the vessel was flushed with nitrogen via vacuum/nitrogen cycles (x 3) and heated under reflux for 2 hours. The dark brown reaction mixture was cooled down to ambient temperature and the crude mixture was partitioned between EtOAc (600 mL) and water (300 mL). The combined organic extract was washed with water (300 mL), brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica, 0 to 30% EtOAc/Petroleum Ether gradient elution) to give 4-[(E)-2-ethoxyvinyl]-6-methylsulfanyl-pyrimidine as an orange oil which crystallised on standing (27.39 g, 74%); 1H NMR (400 MHz, DMSO-d6) delta 8.65 (d, J = 1.2 Hz, 1H), 7.87 (d, J = 12.5 Hz, 1H), 7.18 (d, J = 1.3 Hz, 1H), 5.80 (d, J = 12.5 Hz, 1H), 4.01 (q, J = 7.0 Hz, 2H), 1.28 (t, J = 7.0 Hz, 3H); MS m/z: 197.3 (M+H)+

Reference： [1]Patent: WO2019/148132,2019,A1 .Location in patent: Paragraph 00922; 00923

71
[ 1201905-61-4 ]
3-bromo-6,7-dimethoxyquinolin-4-amine [ No CAS ]
(E)-3-(2-ethoxyvinyl)-6,7-dimethoxyquinolin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In water; acetonitrile; at 110℃; for 16h;Inert atmosphere;	To a stirred solution of compound 3-bromo-6,7-dimethoxyquinolin-4-amine (1.5 g, 5.319 mmol) in ACN:Water (4: 1), was added (E)-2-(2-ethoxyvinyl)-4,4,5,5-tetramethyl-l,3,2- dioxaborolane (2.1 g, 10.0638 mmol) and potasium phosphate (2.25 g, 10.638 mmol) at room temparature. The mixture was purged with argon gas for 15 minutes, then added S-phos (0.160 g, (0815) 0.398 mmol), Palladium(II) acetate (0.036 g, 0.159 mmol) at room temparature, Reaction mixture was stirred for 16 h at 110 C, Progress of the reaction was monitored by TLC. Reaction mixture was cooled to room temparature, Reaction mixture was filtered through celite and filterate was cocentrated under reduced pressure to get the crude compound. The obtained crude was purified by combiflash purifier using 7% methanol in dichloroethane as eluent to afford (E)-3-(2-ethoxyvinyl)-6,7- dimethoxyquinolin-4-amine as an off white solid (0.750 g, Crude). LC-MS (ES) m/z = 275.3 [M+H] +.

Reference： [1]Patent: WO2019/177971,2019,A1 .Location in patent: Paragraph 0423; 0427

72
[ 5424-21-5 ]
[ 1201905-61-4 ]
2-chloro-4-[(E)-2-ethoxyethenyl]-6-methylpyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37.78%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In water; acetonitrile; at 20℃;Inert atmosphere;	To a stirred solution of 2,4-dichloro-6-methylpyrimidine (246.88 mg, 1.439 mmol, 1.20 equiv, 95%), <strong>[1201905-61-4]2-[(E)-2-ethoxyethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane</strong> (250 mg, 1.199 mmol, 1 equiv, 95%) and K3PO4 (535.84 mg, 2.398 mmol, 2.00 equiv, 95%) in MeCN (12.45 mL, 303.230 mmol, 187.63 equiv, 95%) and H2O (4 mL, 210.932 mmol, 364.96 equiv, 95%) were added SPhos (36.27 mg, 0.084 mmol, 0.07 equiv, 95%) and Pd(AcO)2 (8.50 mg, 0.036 mmol, 0.03 equiv, 95%) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for overnight at room temperature under nitrogen atmosphere. The resulting mixture was concentrated to a small volume. The resulting mixture was diluted with brine (20 mL). The resulting mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine (2x20 mL), dried over anhydrous MgSO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EtOAc (5:1) to afford 2-chloro-4-[(E)-2-ethoxyethenyl]-6- methylpyrimidine(100 mg,37.78%) as a light yellow oil.

Reference： [1]Patent: WO2019/148136,2019,A1 .Location in patent: Paragraph 00417

73
[ 1201905-61-4 ]
methyl 6-bromo-7-chloro-2-(trans-4-(dimethylamino)cyclohexyl)-2,4-dimethylbenzo[d][1,3]dioxole-5-carboxylate [ No CAS ]
methyl 7-chloro-2-(trans-4-(dimethylamino)cyclohexyl)-6-(2-ethoxyvinyl)-2,4-dimethylbenzo[d][1,3]dioxole-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; dichloromethane; water; at 100℃; for 24h;Inert atmosphere;	A mixture of methyl 6-bromo-7-chloro-2-(trans-4-(dimethylamino)cyclohexyl)-2.4-dimethylbenzo[d] [l,3]dioxole-5-carboxylate (4.27 g, 9.55 mmol), [1,1'- bis(diphenylphosphino)ferrocene]dichloro palladium(II) complex with dichloromethane (1.55 g, 1.91 mmol), cesium carbonate (9.31 g, 28.6 mmol), l,4-dioxane (35 mL) and water (5 mL) was degassed (four vacuum/nitrogen refill cycles) prior to adding a solution of 2-[(£)-2- ethoxyethenyl]-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (3.78 g, 19.1 mmol) in l,4-dioxane (15 mL). The resulting black reaction mixture was heated at 100 C for 24 h then cooled to room temperature, diluted with ethyl acetate and filtered. The filtrate was washed with water and the aqueous layer was extracted with ethyl acetate three times. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. The residue was purified by flash chromatography (normal phase KP-NH column, gradient 0 to 40% ethyl acetate in heptane) to give the title compound (3.5 g, 84 % yield) as a thick yellowish oil. LCMS [M+H]+ m/z: calc?d 438.2; found 438.3.

Reference： [1]Patent: WO2019/226491,2019,A1 .Location in patent: Paragraph 0066; 0073; 0074

74
[ 1201905-61-4 ]
[ 203569-15-7 ]
(E)-3-(2-ethoxyvinyl)-5-methylisonicotinaldehyde [ No CAS ]
(Z)-3-(2-ethoxyvinyl)-5-methylisonicotinaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 75℃; for 19h;Inert atmosphere;	3-Bromo-5-methylisonicotinaldehyde (9) (172 mg, 0.860 mmol) and tetrakis(triphenylphosphine)palladium(0) (102 mg, 0.0883 mmol) were dissolved in 1,4-dioxane (3 mL) under a nitrogen atmosphere, then (E)-2-ethoxyvinylboronic acid pinacol ester (10) (0.36 mL, 1.7 mmol) was added. Caesium carbonate (1.42 g, 4.36 mmol) was dissolved in water (1 mL) under a nitrogen atmosphere and was added dropwise to the reaction mixture. The mixture was heated at 75 C for 19 h. After cooling to room temperature the mixture was quenched with saturated aqueous ammonium chloride solution (15 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over magnesium sulfate and the solvents were evaporated under reduced pressure. Purification was accomplished by FCC using 3:1 hexanes-ethyl acetate to give 146 mg (0.763 mmol, 89%) of 11 as a yellow oil. The product consisted of a mixture of E- and Z-isomers at the ratio 4:1. 1H NMR (400 MHz, CDCl3): delta = 10.47 (s, 1H, CHO (E)), 10.36 (s, 1H, CHO (Z)), 8.84 (s, 1H, 2-H (Z)), 8.53 (s, 1H, 2-H (E)), 8.35 (s, 1H, 6-H (E)), 8.33 (s, 1H, 6-H (Z)), 6.83 (d, J = 12.8 Hz, 1H, 2?-H (E)), 6.42 (d, J = 7.0 Hz, 1H, 2?-H (Z)), 6.29 (d, J = 12.8 Hz, 1H, 1?-H (E)), 5.65 (d, J = 7.0 Hz, 1H, 1?-H (Z)), 4.00 - 3.93 (m, 4H, CH2CH3 (E and Z)), 2.51 (s, 3H, 5-CH3 (E)), 2.50 (s, 3H, 5-CH3 (Z)), 1.37 (t, J = 7.0 Hz, 3H, CH2CH3 (E)), 1.29 (t, J = 7.1 Hz, 3H, CH2CH3 (Z)) ppm. 13C NMR (101 MHz, CDCl3): delta = 193.8 (CHO (Z)), 193.4 (CHO (E)), 152.5 (C-2? (E)), 150.2 (C-2 (Z)), 150.0 (C-6 (E)), 149.9 (C-2? (Z)), 149.8 (C-6 (Z)), 147.6 (C-2 (E)), 136.0 (C-4 (Z)), 135.8 (C-4 (E)), 132.5 (C-3 (E)), 132.2 (C-5 (E)), 131.7 (C-5 (Z)), 131.4 (C-3 (Z)), 99.1 (C-1? (E)), 98.0 (C-1? (Z)), 69.6 (CH2CH3 (Z)), 66.3 (CH2CH3 (E)), 17.3 (5-CH3 (Z)), 17.0 (5-CH3 (E)), 15.3 (CH2CH3 (Z)), 14.8 (CH2CH3 (E)) ppm. IR (film): nu = 2979, 1773, 1702, 1630, 1443, 1384, 1184, 1101, 1024, 951, cm-1. HRMS (ESI): m/z = 192.1019 [M + H]+ (calcd. for C11H14NO2 +: 192.1019). HPLC purity: > 99% (lambda = 210 nm), > 99% (lambda = 254 nm).

Reference： [1]Letters in Organic Chemistry,2019,vol. 16,p. 931 - 934

75
[ 1201905-61-4 ]
[ 82463-75-0 ]
C₁₃H₁₇NO₄ [ No CAS ]