Name: 1073371-99-9|Methyl 2-hydroxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate|98%
Brand: Ambeed
SKU: A722212
Price: 21.0 USD
Availability: InStock
Rating: 99 (30 reviews)

1
[ 1073371-99-9 ]
[ 1374260-86-2 ]
[ 74-88-4 ]
[ 1374263-36-1 ]

Yield	Reaction Conditions	Operation in experiment
57%	Stage #1: methyl 2-hydroxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate; tert-butyl {1-[4-(2-chloro-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate With bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II); sodium carbonate In water; N,N-dimethyl-formamide at 160℃; for 1h; Microwave irradiation; Stage #2: methyl iodide With potassium carbonate In water; N,N-dimethyl-formamide at 20℃; for 8.5h;	70.1 Step 1: Preparation of methyl 4-[3-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-2-yl]-2-hydroxybenzoate A mixture of tert-butyl {1-[4-(2-chloro-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl)phenyl]cyclobutyl}carbamate (55 mg, 0.092 mmol), methyl 2-hydroxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (48 mg, 0.18 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (7 mg, 0.009 mmol), and 2M Na2CO3 aq. (0.092 mL, 0.18 mmol) in DMF (2.5 mL) was treated with microwave (160° C. for 1 hour). The reaction mixture was added potassium carbonate (30 mg, 0.22 mmol) and iodomethane (0.050 mL, 0.80 mmol) and stirred at r.t for 8.5 hours. The mixture was diluted with AcOEt, washed with water (*3), brine, dried over Na2SO4, then filtrated through Celite pad. The filtrate was concentrated and the residue was purified by preparative thin-layer chromatography (n-hexane/AcOEt=1:2) to afford the desired product (33 mg, 57%) as a pale yellow solid. 1HNMR (CDCl3) 400 MHz δ: 8.16 (dd, J=8.0 Hz and 1.1 Hz, 1H), 8.01 (d, J=4.0 Hz, 1H), 7.70 (d, J=8.6 Hz, 1H), 7.39 (d, J=8.6 Hz, 2H), 7.31 (td, J=8.0 Hz and 1.1 Hz, 2H), 7.18-7.16 (m, 2H), 7.11-7.07 (m, 1H), 6.95 (d, J=8.0 Hz, 1H), 6.80-6.76 (m, 1H), 6.59 (dd, J=7.7 Hz and 4.9 Hz, 1H), 6.24 (s, 1H), 5.09 (br s, 1H), 3.92 (s, 3H), 2.59-2.40 (m, 4H), 2.19-2.12 (m, 1H), 1.93-1.88 (m, 1H), 1.40 (br s, 9H). LCMS: 630 [M+H].

Reference： [1]Current Patent Assignee: MERCK & CO INC - US2012/108574, 2012, A1 Location in patent: Page/Page column 117

2
[ 1073371-99-9 ]
[ 1429313-06-3 ]
[ 1429313-07-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	With tripotassium phosphate tribasic; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane In 1,4-dioxane; lithium hydroxide monohydrate at 110℃; for 0.666667h;	Synthesis of Methyl 4-[5-(2,2,3,3,13,13-hexamethyl-11-oxo-4,7,12-trioxa-10-aza-3-silatetradecan-10-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-2-hydroxybenzoate (18) Tert-Butyl N-{3-bromopyrazolo [1,5-a]pyrimidin-5-yl}-N-(2-{2-[(tert-butyldimethylsilyl)oxy]ethoxy}ethyl)carbamate (8) (2.15g, 4.17mmol) and Methyl 2-hydroxy-4 (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (12) (2.32g, 8.34mmol) were suspended together with Pd2 (dba)3 (38mg, 0.04mmol), XPhos (0.24g, 0.50mmol) and potassium phosphate (3.54g, 16.68mmol) in 1,4-dioxane (27mL) and water (11mL). The reaction was running for 40min at 110°C. After diluting with ethyl acetate layers were separated, the organic one was washed with water and brine and dried over MgSO4. The solvent was evaporated in vacuo. Purification was performed by silica gel column chromatography with a mobile phase of n-hexane an ethyl acetate (ratio gradually ranging from 5:1 to 1:1). The white solid obtained was the desired compound (2.23g, 91%). 1H NMR (250MHz, DMSO-d6): δ 10.62 (s, 1H, OH), 8.99 (d, J=7.8Hz, 1H, HetH), 8.74 (s, 1H, HetH), 7.79 (d, J=8.1Hz, 1H, PhH), 7.71-7.66 (m, 2H, PhH), 7.49 (d, J=7.8Hz, 1H, HetH), 4.23 (t, J=6.2Hz, 2H, CH2), 3.90 (s, 3H, OCH3), 3.77 (t, J=6.2Hz, 2H, CH2), 3.61 (t, J=5.0Hz, 2H, CH2), 3.48 (t, J=4.9Hz, 2H, CH2), 1.53 (s, 9H, (CH3)3), 0.76 (s, 9H, (CH3)3),-0.08 (s, 6H, Si(CH3)2) ppm.
64%	With tripotassium phosphate tribasic In 1,4-dioxane at 110℃; for 1h;	1 Preparation of intermediate 7 A solution of intermediate 3 (4.25 g, 8.24 mmol) in 1 ,4-dioxane (8.24 ml) and a solution of potassiumphosphate (7.78 g, 36.64 mmol) in water (7.33 ml) were added to crude intermediate 6 (9.16 mmol). The mixture was stirred at 1 10°C for 1 hour. The reaction mixture was cooled, diluted with ethyl acetate and the organic layer was washed with water and brine. The organic layer was dried, filtered and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography over silica gel using heptane and ethyl acetate as eluents. The product fractions were collected and the solvent was evaporated.Yield: 3.46 g of intermediate 7 (64%)LCMS method 1 : MH+ = 487 (MW-Boc), RT = 2.544 min
3.46 g	With tripotassium phosphate tribasic In 1,4-dioxane; lithium hydroxide monohydrate at 110℃; for 1h;	1 Preparation of Intermediate 7 Preparation of Intermediate 7 A solution of intermediate 3 (4.25 g, 8.24 mmol) in 1,4-dioxane (8.24 ml) and a solution of potassiumphosphate (7.78 g, 36.64 mmol) in water (7.33 ml) were added to crude intermediate 6 (9.16 mmol). The mixture was stirred at 110° C. for 1 hour. The reaction mixture was cooled, diluted with ethyl acetate and the organic layer was washed with water and brine. The organic layer was dried, filtered and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography over silica gel using heptane and ethyl acetate as eluents. The product fractions were collected and the solvent was evaporated. [0736] Yield: 3.46 g of intermediate 7 (64%) [0737] LCMS method 1: MH+=487 (MW-Boc), RT=2.544 min

With tripotassium phosphate tribasic; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane In 1,4-dioxane; lithium hydroxide monohydrate at 110℃; for 0.666667h;

Reference： [1]Berger, Benedict-Tilman; Celik, Ibrahim Ethem; Greco, Francesco Aleksy; Hanke, Thomas; Knapp, Stefan; Krämer, Andreas; Kurz, Christian Georg; Tjaden, Amelie [European Journal of Medicinal Chemistry, 2020, vol. 208]
[2]Current Patent Assignee: CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC; BANQUE DE VIZILLE - WO2013/45653, 2013, A1 Location in patent: Page/Page column 56; 57
[3]Current Patent Assignee: BANQUE DE VIZILLE; CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC - US2014/303159, 2014, A1 Location in patent: Paragraph 0734-0737
[4]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

3
[ 89-86-1 ]
[ 1073371-99-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sulfuric acid / 0 °C / Reflux 2: triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere 3: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane / 1,4-dioxane / 0.5 h / 110 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1: sulfuric acid / 0 °C / Reflux 2: triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere 3: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane / 1,4-dioxane / 0.5 h / 110 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1: sulfuric acid / 16 h / Reflux 2: 4‐dimethylaminopyridine; pyridine / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 3: anhydrous potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct / 1,4-dioxane / 3.5 h / 100 °C

Multi-step reaction with 3 steps 1: sulfuric acid / 16 h / Reflux 2: 4‐dimethylaminopyridine; pyridine / dichloromethane / 16 h / 0 - 20 °C 3: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; anhydrous potassium acetate / 1,4-dioxane / 3.5 h / 100 °C

Reference： [1]Current Patent Assignee: CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC; BANQUE DE VIZILLE - WO2013/45653, 2013, A1
[2]Current Patent Assignee: BANQUE DE VIZILLE; CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC - US2014/303159, 2014, A1
[3]Berger, Benedict-Tilman; Celik, Ibrahim Ethem; Greco, Francesco Aleksy; Hanke, Thomas; Knapp, Stefan; Krämer, Andreas; Kurz, Christian Georg; Tjaden, Amelie [European Journal of Medicinal Chemistry, 2020, vol. 208]
[4]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

4
[ 2150-47-2 ]
[ 1073371-99-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere 2: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane / 1,4-dioxane / 0.5 h / 110 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 0 - 20 °C / Inert atmosphere 2: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane / 1,4-dioxane / 0.5 h / 110 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: 4‐dimethylaminopyridine; pyridine / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 2: anhydrous potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct / 1,4-dioxane / 3.5 h / 100 °C

Multi-step reaction with 2 steps 1: 4‐dimethylaminopyridine; pyridine / dichloromethane / 16 h / 0 - 20 °C 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; anhydrous potassium acetate / 1,4-dioxane / 3.5 h / 100 °C

Reference： [1]Current Patent Assignee: CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC; BANQUE DE VIZILLE - WO2013/45653, 2013, A1
[2]Current Patent Assignee: BANQUE DE VIZILLE; CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC - US2014/303159, 2014, A1
[3]Berger, Benedict-Tilman; Celik, Ibrahim Ethem; Greco, Francesco Aleksy; Hanke, Thomas; Knapp, Stefan; Krämer, Andreas; Kurz, Christian Georg; Tjaden, Amelie [European Journal of Medicinal Chemistry, 2020, vol. 208]
[4]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

5
[ 73183-34-3 ]
[ 149878-72-8 ]
[ 1073371-99-9 ]

Yield	Reaction Conditions	Operation in experiment
80%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; anhydrous potassium acetate In 1,4-dioxane at 100℃; for 3.5h;	Synthesis of Methyl 2-hydroxy-4(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (12). To a solution of methyl-2-hydroxy-4-(((trifluoromethyl)sulfonyl)oxy)benzoate (11) (2.29g, 7.61mmol) in dry 1,4-dioxane (50mL), bis(pinacolato)diboron (2.90g, 11.42mmol), potassium acetate (2.24g, 22.83mmol) and Pd (dppf)Cl2·DCM (0.31g, 0.38mmol) were added. The reaction solution was flushed with argon for 10min and stirred at 100°C for 3.5h. Subsequently the reaction was diluted with ethyl acetate and water and the layers were separated. The organic layer was washed with brine and dried over MgSO4. After removal of the solvent under reduced pressure, the crude product was purified with silica gel column chromatography with a mobile phase of n-hexane and ethyl acetate (ratio gradually ranging from 1:0 to 30:1). The title compound was obtained as a white solid (1.69g, 80%). 1H NMR (500MHz, DMSO-d6): δ 10.36 (s, 1H, OH), 7.76 (d, J=7.8Hz, 1H, PhH), 7.31-7.11 (m, 2H, PhH), 3.88 (s, 3H, OCH3), 1.29 (s, 12H, CH3) ppm.
	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane In 1,4-dioxane at 110℃; for 0.5h; Inert atmosphere;	1 Preparation of intermediate 6 1 ,4-Dioxane (27 ml) was degassed by bubbling nitrogen gas through it. Intermediate 5 (2.75 g, 9.16 mmol), bis(pinacolato)diboron (2.33 g, 9.16 mmol), tris(dibenzylideneacetone)dipalladium(0) (82 mg, 0.09 mmol) and 2-(dicyclohexylphosphino)-2',4',6'-triisopropylbiphenyl (348 mg, 0.73 mmol) were added. The suspension was stirred under nitrogen atmosphere at 1 10°C for 30 minutes. The reaction mixture was cooled and was used as such in the next step.LCMS method 1 : MH+ = 279, RT = 1 .599 min
	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane In 1,4-dioxane at 110℃; for 0.5h; Inert atmosphere;	1 Preparation of Intermediate 6 Preparation of Intermediate 6 [0731] [0732] 1,4-Dioxane (27 ml) was degassed by bubbling nitrogen gas through it. Intermediate 5 (2.75 g, 9.16 mmol), bis(pinacolato)diboron (2.33 g, 9.16 mmol), tris(dibenzylideneacetone)dipalladium(0) (82 mg, 0.09 mmol) and 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (348 mg, 0.73 mmol) were added. The suspension was stirred under nitrogen atmosphere at 110° C. for 30 minutes. The reaction mixture was cooled and was used as such in the next step. [0733] LCMS method 1: MH+=279, RT=1.599 min

With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; anhydrous potassium acetate In 1,4-dioxane at 100℃; for 3.5h;

Reference： [1]Berger, Benedict-Tilman; Celik, Ibrahim Ethem; Greco, Francesco Aleksy; Hanke, Thomas; Knapp, Stefan; Krämer, Andreas; Kurz, Christian Georg; Tjaden, Amelie [European Journal of Medicinal Chemistry, 2020, vol. 208]
[2]Current Patent Assignee: CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC; BANQUE DE VIZILLE - WO2013/45653, 2013, A1 Location in patent: Page/Page column 56
[3]Current Patent Assignee: BANQUE DE VIZILLE; CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC - US2014/303159, 2014, A1 Location in patent: Paragraph 0731-0733
[4]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

6
[ 1073371-99-9 ]
[ 1429313-08-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tripotassium phosphate tribasic / 1,4-dioxane / 1 h / 110 °C 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 1 h / 20 °C
	Multi-step reaction with 2 steps 1: tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 110 °C 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 1 h / 20 °C
	Multi-step reaction with 2 steps 1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C

Multi-step reaction with 2 steps 1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C

Reference： [1]Current Patent Assignee: CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC; BANQUE DE VIZILLE - WO2013/45653, 2013, A1
[2]Current Patent Assignee: BANQUE DE VIZILLE; CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC - US2014/303159, 2014, A1
[3]Berger, Benedict-Tilman; Celik, Ibrahim Ethem; Greco, Francesco Aleksy; Hanke, Thomas; Knapp, Stefan; Krämer, Andreas; Kurz, Christian Georg; Tjaden, Amelie [European Journal of Medicinal Chemistry, 2020, vol. 208]
[4]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

7
[ 1073371-99-9 ]
[ 1429313-09-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tripotassium phosphate tribasic / 1,4-dioxane / 1 h / 110 °C 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 1 h / 20 °C 3: di-isopropyl azodicarboxylate; triphenylphosphine / 2-methyltetrahydrofuran; toluene / 3 h / 90 °C
	Multi-step reaction with 3 steps 1: tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 110 °C 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 1 h / 20 °C 3: di-isopropyl azodicarboxylate; triphenylphosphine / 2-methyltetrahydrofuran; toluene / 3 h / 90 °C
	Multi-step reaction with 3 steps 1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C / Inert atmosphere

Multi-step reaction with 3 steps 1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C

Reference： [1]Current Patent Assignee: CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC; BANQUE DE VIZILLE - WO2013/45653, 2013, A1
[2]Current Patent Assignee: BANQUE DE VIZILLE; CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC - US2014/303159, 2014, A1
[3]Berger, Benedict-Tilman; Celik, Ibrahim Ethem; Greco, Francesco Aleksy; Hanke, Thomas; Knapp, Stefan; Krämer, Andreas; Kurz, Christian Georg; Tjaden, Amelie [European Journal of Medicinal Chemistry, 2020, vol. 208]
[4]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

8
[ 1073371-99-9 ]
[ 1429312-70-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: tripotassium phosphate tribasic / 1,4-dioxane / 1 h / 110 °C 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 1 h / 20 °C 3: di-isopropyl azodicarboxylate; triphenylphosphine / 2-methyltetrahydrofuran; toluene / 3 h / 90 °C 4: lithium hydroxyde monohydrate / tetrahydrofuran; methanol / 50 °C
	Multi-step reaction with 4 steps 1.1: tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 1 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine / 2-methyltetrahydrofuran; toluene / 3 h / 90 °C 4.1: lithium hydroxyde monohydrate / tetrahydrofuran; methanol / 50 °C 4.2: pH 3
	Multi-step reaction with 5 steps 1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C / Inert atmosphere 4: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C

Multi-step reaction with 5 steps 1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C

Reference： [1]Current Patent Assignee: CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC; BANQUE DE VIZILLE - WO2013/45653, 2013, A1
[2]Current Patent Assignee: BANQUE DE VIZILLE; CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC - US2014/303159, 2014, A1
[3]Berger, Benedict-Tilman; Celik, Ibrahim Ethem; Greco, Francesco Aleksy; Hanke, Thomas; Knapp, Stefan; Krämer, Andreas; Kurz, Christian Georg; Tjaden, Amelie [European Journal of Medicinal Chemistry, 2020, vol. 208]
[4]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

9
[ 1073371-99-9 ]
[ 1429313-21-2 ]
[ 1429313-22-3 ]

Yield	Reaction Conditions	Operation in experiment
44%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; XPhos In 1,4-dioxane; water at 80℃; for 2h; Inert atmosphere;	4 Preparation of intermediate 24 A mixture of 1 ,4-dioxane and water (3:1 , 62 ml) was degassed by bubbling nitrogen gas through the mixture. Intermediate 23 (3.83 g, 6.23 mmol), methyl 2-hydroxy-4-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)benzoate (2.25 g, 8.10 mmol), tris(dibenzylideneacetone)dipalladium(0) (55 mg, 0.06 mmol), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (Xphos) (1 19 mg, 0.25 mmol) and potassium phosphate tribasic (5.28 g, 4 eq.) were added and the mixture was stirred under nitrogen gas at 80°C for 2 hours. The reaction mixture was cooled, diluted with ethyl acetate and the organic layer was washed with brine. The organic layer was dried, filtered and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography over silica gel using heptane and ethyl acetate as eluents. The product fractions were collected and the solvent was evaporated.Yield: 1 .88 g of intermediate 24 (44%)LCMS method 1 : MH+ = 572 (MW-Me-Boc), RT = 2.303 min
44%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; XPhos In 1,4-dioxane; water at 80℃; for 2h; Inert atmosphere;	4 Preparation of Intermediate 24 A mixture of 1,4-dioxane and water (3:1, 62 ml) was degassed by bubbling nitrogen gas through the mixture. Intermediate 23 (3.83 g, 6.23 mmol), methyl 2-hydroxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (2.25 g, 8.10 mmol), tris(dibenzylideneacetone)dipalladium(0) (55 mg, 0.06 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (Xphos) (119 mg, 0.25 mmol) and potassium phosphate tribasic (5.28 g, 4 eq.) were added and the mixture was stirred under nitrogen gas at 80° C. for 2 hours. The reaction mixture was cooled, diluted with ethyl acetate and the organic layer was washed with brine. The organic layer was dried, filtered and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography over silica gel using heptane and ethyl acetate as eluents. The product fractions were collected and the solvent was evaporated. [0818] Yield: 1.88 g of intermediate 24 (44%) [0819] LCMS method 1: MH+=572 (MW-Me-Boc), RT=2.303 min

Reference： [1]Current Patent Assignee: CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC; BANQUE DE VIZILLE - WO2013/45653, 2013, A1 Location in patent: Page/Page column 70
[2]Current Patent Assignee: BANQUE DE VIZILLE; CRÉDIT INDUSTRIEL ET COMMERCIAL - CIC - US2014/303159, 2014, A1 Location in patent: Paragraph 0816-0819

10
[ 18179-39-0 ]
[ 73183-34-3 ]
[ 1073371-99-9 ]

Yield	Reaction Conditions	Operation in experiment
81%	With trans-bis(triphenylphosphine)palladium dichloride; potassium acetate; In 1,4-dioxane; at 120℃; for 16h;Inert atmosphere;	Scheme 2: Synthetic path for 3-hydroxy-(methoxycarbonyl) phenylboronic acid pinacol ester (2):Dioxane (450 mL) was added to a flask containing iodide 1 (25.0 g, 90.0 mmol) , bis (pinacolato) diboron (25.1 g, 98.8 mmol) , KOAc (29.1 g, 297 mmol), and PdCl2(PPh3)2 (1.26 g, 1.80 mmol) . The resulting suspension was deoxygenated by nitrogen bubbling at room temperature for 30 min, then immersed in oil bath preheated to 120 C, and stirred at reflux for 16 h. After cooled down to room temperature, the mixture was filtered to remove the insoluble material using AcOEt to rinse the filter cake. The filtrate was evaporated to give brown oil which solidified slowly at room temperature. The crude product was purified by flash silica gel column chromatography (hexanes/AcOEt, 10:1) followed by recrystallization from hot hexanes to provide compound 2 as colorless crystals (20.3 g, 73.1 mmol, 81%). 1H NMR (400 MHz, CDCl3), [ppm] : 1.34 (s, 12H) , 3.94 (s, 3H) , 7.27 (d, J = 8.1 Hz, 1H) , 7.41 (s, 1H) , 7.80 (d, J = 7.9 Hz, 1H) , 10.6 (s, 1H) ; 13C{1H} NMR (100 MHz, CDCl3) , [ppm] : 24.8, 52.3, 84.2, 114.2, 123.8, 124.7, 128.9, 160.7, 170.5; (Carbon directly bonded to boron was not observed) . IR (ATR) , v_max [cm-1] : 3177 (br) , 2982 (w) , 1676 (m) , 1619 (w), 1557 (w) , 1502 (w) , 1438 (w) , 1371 (sh) , 1359 (s) , 1329 (s), 1282 (m) , 1220 (m) , 1192 (m) , 1159 (sh) , 1136 (s), 1099 (s)961 (w) , 920 (m) , 850 (m) , 821 (w) , 788 (s) , 712 (s) , 638 (m) , 663 (m) , 562 (m), 547 (m) , 500 (w) , 467 (w) .

Reference： [1]Journal of the American Chemical Society,2014,vol. 136,p. 8863 - 8866
[2]Patent: WO2015/195179,2015,A2 .Location in patent: Paragraph 00155; 00156

11
[ 615-59-8 ]
[ 1073371-99-9 ]
[ 1613451-77-6 ]

Yield	Reaction Conditions	Operation in experiment
87%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; cesium fluoride; In 1,4-dioxane; water;	Boronate 2 (4.67 g, 16.8 mmol) and dibromide 3a (1.10 mL, 7.98 mmol) were subjected to Suzuki-Miyaura coupling. After cooling down to room temperature, the reaction mixture was partitioned between CH2Cl2 (300 mL) and 10percent NH4Cl (60 mL). The organic layer was isolated and the aqueous layer was extracted with CH2Cl2 (2 x 60 mL) . The organic layers were combined, dried over Na2SO4, filtered, and evaporated in vacuo to provide a dark brown solid, which was then subjected to a filtration through a pad of silica gel (CH2Cl2). The filtrate was evaporated in vacuo and the resulting light yellow solid was recrystallized from hot toluene to provide 4a as white needles (2.72 g, 5.94 mmol, 87percent). NMR (500 MHz, CDCl3), [ppm]: 2.35 (s, 3H), 3.98 and 3.99 (two s, 6H in total), 6.88 (dd, J = 6.9, 1.4 Hz, 1H), 6.99 (d, J = 1.3 Hz, 1H), 7.16 (dd, J = 8.2, 1.5 Hz, 1H), 7.25 (d, J = 1.4 Hz, 1H), 7.31 (d, J = 7.8 Hz, 1H), 7.50 (d, J = 7.9 Hz, 1H), 7.53 (s, 1H), 7.89 (d, J = 7.9 Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 10.83 and 10.84(two s, 2H in total); 13C{1H} NMR (126 MHz, CDCl30, [ppm]: 20.5, 52.3, 52.3, 111.1, 111.2, 115.7, 118.1, 118.1, 120.4, 124.7, 129.3, 129.7, 129.9, 130.3, 135.8, 139.2, 140.8, 148.0, 149.1, 161.3, 161.8, 170.5.

Reference： [1]Journal of the American Chemical Society,2014,vol. 136,p. 8863 - 8866
[2]Patent: WO2015/195179,2015,A2 .Location in patent: Paragraph 00166; 00167

12
[ 1073371-99-9 ]
[ 1310923-60-4 ]
[ 1613451-78-7 ]

Yield	Reaction Conditions	Operation in experiment
82%	With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; cesium fluoride In 1,4-dioxane; water at 90℃; Inert atmosphere;
82%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; cesium fluoride In 1,4-dioxane; water	2 Boronate 2 (1.50 g, 5.39 mmol) and dibromide 3b (0.901 g, 2.57 mmol) were subjected to Suzuki-Miyaura coupling. After cooled down to room temperature, the reaction mixture was partitioned between AcOEt (100 mL) and 10% NH4Cl (50 mL) . The organic layer was isolated and the aqueous layer was extracted with AcOEt (3 x 50 mL) . The organic layers were combined, washed with brine (50 mL) , dried over Na2SO4, filtered, and evaporated in vacuo to provide a dark grey solid, which was then subjected to flash silica gel chromatography [CH2Cl2, then CH2Cl2/AcOEt (50:1)] . The fractions containing compound 4b were collected and evaporated in vacuo. The resulting light yellow solid was dissolved in hot toluene (10 mL) and the solution was cooled to room temperature to form white precipitates over a period of 40 min . Hexanes (10 mL) was added dropwise to form additional precipitate before the precipitate was collected by filtration then rinsed by toluene/hexanes (1:1, 40 mL) then hexanes (40 mL). The filtrate was evaporated and the resulting yellow solid was subjected to recrystallization in the same manner as above using 2 mL of toluene and 2 mL of hexanes. The first and second crops were combined and dried under vacuum to provide compound 4b as a white powder (1.04 g, 2.10 mmol, 82%). 1H NMR (500 MHz, CDCl3), [ppm]: 1.48 (s, 9H), 3.97 and 3.98 (two s, 6H in total), 6.59 (s, 1H), 6.92 (dd, J = 8.1, 1.5 Hz, 1H), 7.02 (d, J = 1.4 Hz, 1H), 7.20 (dd, J = 8.3, 1.6 Hz, 1H), 7.26 (d, J = 8.0 Hz, 1H), 7.27 (d, J = 1.5 Hz, 1H), 7.34 (dd, J = 8.0, 1.6 Hz, 1H), 7.87 (d, J = 8.2 Hz, 1H), 7.94 (d, J = 8.1 Hz, 1H), 8.44 (s, 1H), 10.81 (s, 1H), 10.90 (s, 1H); 13C{1H} NMR (126 MHz, CDCl3), [ppm]: 28.2, 52.3, 52.4, 80.9, 111.3, 111.8, 115.8, 118.1, 118.3, 118.7, 120.0, 121.8, 130.0, 130.2, 130.2, 130.7, 135.6, 140.4, 145.5, 147.7, 152.6, 161.7, 161.9, 170.2, 170.4.

Reference： [1]Fracaroli, Alejandro M.; Furukawa, Hiroyasu; Suzuki, Mitsuharu; Dodd, Matthew; Okajima, Satoshi; Gándara, Felipe; Reimer, Jeffrey A.; Yaghi, Omar M. [Journal of the American Chemical Society, 2014, vol. 136, # 25, p. 8863 - 8866]
[2]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - WO2015/195179, 2015, A2 Location in patent: Paragraph 00170; 00171

13
[ 1073371-99-9 ]
[ 1613451-75-4 ]
[ 1613451-79-8 ]

Yield	Reaction Conditions	Operation in experiment
76%	With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; cesium fluoride In 1,4-dioxane; water at 90℃; Inert atmosphere;
76%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; cesium fluoride In 1,4-dioxane; water	2 Boronate 2 (3.20 g, 11.5 mmol) and dibromide 3c (2.01 g, 5.51 mmol) were subjected to Suzuki-Miyaura coupling. After cooling to room temperature, the reaction mixture was partitioned between AcOEt (200 mL) and 10% NH4Cl (50 mL) . The organic layer was isolated and the aqueous layer was extracted with AcOEt (3x25 mL) . The organic layers were combined, washed with brine (50 mL) , dried over Na2SO4, filtered, and evaporated in vacuo to provide a black solid, which was then subjected to flash silica gel chromatography [CH2Cl2, then CH2Cl2/AcOEt (50:1)]. The fractions containing compound 4c were collected and evaporated in vacuo. The resulting light yellow solid was dissolved in toluene (20 mL) , to which hexanes (20 mL) was added dropwise to form a white precipitate. The precipitate was collected by filtration, rinsed with toluene/hexanes (1:1, 10 mL) , then dried in vacuo to provide pure 4c as a white powder (2.14 g, 4.21 mmol, 76%). 1H NMR (400 MHz, CDCl3), [ppm]: 1.42 (s, 9H), 3.97 (s, 6H), 4.33 (d, J = 3.5 Hz, 2H), 4.79 (s, 1H), 6.85 (d, J = 7.8 Hz, 1H), 6.94 (s, 1H), 7.14 (d, J = 7.9 Hz, 1H), 7.29 (s, 1H), 7.29 (d, J = 7.7 Hz, 1H), 7.55 (d, J = 7.3 Hz, 1H), 7.68 (s, 1H), 7.87-7.90 (two overlapping d, 2H), 10.82 and 10.84 (two s, 2H); 13C{1H} NMR (100 MHz, CDCl3) , [ppm] : 28.3, 42.3, 52.3, 52.3, 79.6, 111.4, 111.4, 115.7, 117.9, 118.0, 120.2, 126.0, 127.0, 129.9, 130.2, 130.3, 136.6, 139.6, 140.2, 147.6, 147.9, 155.7, 161.4, 161.8, 170.3, 170.4.

Reference： [1]Fracaroli, Alejandro M.; Furukawa, Hiroyasu; Suzuki, Mitsuharu; Dodd, Matthew; Okajima, Satoshi; Gándara, Felipe; Reimer, Jeffrey A.; Yaghi, Omar M. [Journal of the American Chemical Society, 2014, vol. 136, # 25, p. 8863 - 8866]
[2]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - WO2015/195179, 2015, A2 Location in patent: Paragraph 00173

14
[ 1073371-99-9 ]
[ 1613451-76-5 ]
[ 1613451-80-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; cesium fluoride In 1,4-dioxane; water at 90℃; Inert atmosphere;
90%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; cesium fluoride In 1,4-dioxane; water	2 Boronate 2 (1.2 g, 4.3 mmol) and dibromide 3d (0.80 g, 2.1 mmol) were subjected to Suzuki-Miyaura coupling. After cooling to room temperature, the reaction mixture was partitioned between CH2Cl2 (300 mL) and 10% NH4Cl (60 mL) . The organic layer was isolated and the aqueous layer was extracted with CH2Cl2 (2 x 60 mL). The organic layers were combined, dried over Na2SO4, filtered, and evaporated in vacuo to provide a dark brown solid, which was then subjected to a filtration through a pad of silica gel (CH2Cl2) . The filtrate was evaporated in vacuum esulting light yellow solid was subjected to flash silica gel chromatography [hexanes/AcOEt (90:10)]. Solvent evaporation in vacuum to provide pure 4d as a white powder (1.0 g, 1.9 mmol, 90%). 1H NMR (400 MHz, CDCl3), [ppm] 1.45 (d, J = 19.7 Hz, 9H), 2.72 (d, J = 29.3 Hz, 3H), 3.98 (s, 6H), 4.48 (d, J = 24.4 Hz, 2H), 6.83 (d, J = 6.9 Hz, 1H), 6.94 (s, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7.23, (s, 1H), 7.31 (d, J = 7.9 Hz, 1H), 7.55 (m, 2H), 7.90 (m, 2H), 10.83 (s, 2H).

Reference： [1]Fracaroli, Alejandro M.; Furukawa, Hiroyasu; Suzuki, Mitsuharu; Dodd, Matthew; Okajima, Satoshi; Gándara, Felipe; Reimer, Jeffrey A.; Yaghi, Omar M. [Journal of the American Chemical Society, 2014, vol. 136, # 25, p. 8863 - 8866]
[2]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - WO2015/195179, 2015, A2 Location in patent: Paragraph 00176

15
[ 1073371-99-9 ]
[ 1314936-94-1 ]
3,4"-dihydroxy-2',3'-dimethoxy [1,1':4',1"-terphenyl]-4-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62.1%	Stage #1: methyl 2-hydroxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate; [1,1'-biphenyl]-4'-monol-4-bromo-2,3-dimethoxy With potassium fluoride dihydrate In 1,4-dioxane for 0.166667h; Inert atmosphere; Stage #2: With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In 1,4-dioxane Inert atmosphere; Reflux;	4.1.2. General parallel procedure a (Schemes 1-4) General procedure: The appropriate bromo derivatives (1 eq.), appropriate phenyl boronic acids (1.5 eq.) and KF*2H2O (3.0 eq.) were dissolved in dioxane and the three resulting mixtures were deoxygenated with a stream of N2. After 10 min, PdCl2(dppf) (0.05 eq.) was added, and each mixture was brought to reflux and stirred under N2 for 5-22 h until the reaction was complete, followed by detection using TLC. Then, each solution was cooled to room temperature. Next, each solution was poured into a mixture of H2O and ethyl acetate, and the two phases were separated. The aqueous layer was washed with ethyl acetate, and the organic phases were combined and washed with brine. The ethyl acetate layer was dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. Each crude product was purified via chromatography or Sephadex LH-20.

Reference： [1]Qiu, Jin; Zhao, Baobing; Zhong, Wanxia; Shen, Yuemao; Lin, Houwen [European Journal of Medicinal Chemistry, 2015, vol. 94, p. 427 - 435]

16
[ 22717-56-2 ]
[ 73183-34-3 ]
[ 1073371-99-9 ]

Yield	Reaction Conditions	Operation in experiment
41.1%		General procedure: The appropriate bromo derivatives (1 eq.) and 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (1.1 eq.) and KAc (3.0 eq.) were dissolved in dioxane, and the three resulting mixtures were deoxygenated under a stream of N2. After 10 min, PdCl2(dppf) (0.05 eq.) was added, and each mixture was brought to 60-80 C andstirred under N2 for 2-4 h until the reaction was complete, followedby detection using TLC. After the reaction was finished,without further treatment the crude product was subjected to asecond coupling reaction.
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 140℃; for 0.333333h;Microwave irradiation;	In a microwave vial, <strong>[22717-56-2]methyl 4-bromo-2-hydroxybenzoate</strong> (250 mg, 1.08 mmol),bis(pinacolato)diboron (330 mg, 1.30 mmol), potassium acetate (425 mg, 4.33 mmol),PdCI2(dppf)-CH2CI2 adduct (44.2 mg, 0.05 mmol) and 1 ,4-dioxane (6 ml) were combined. The reaction vial was then irradiated at 140 00 for 20 minutes in microwave reactor.The reaction mixture was then cooled to room temperature, diluted with EtOAc and brine (10 ml) and filtered through a 0.45 uM PTFE frit. The layers were then separated and the organiclayer was passed through a hydrophobic frit, concentrated and purified via 5i02 chromatogaphy (ISCO Combiflash Rf and eluted with 0 to 10% methanol in DCM over 20 minutes, 25 g column) to yield the desired compound. MS (mlz) 279.1.

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 94,p. 427 - 435
[2]Patent: WO2017/6295,2017,A1 .Location in patent: Page/Page column 134

17
[ 1073371-99-9 ]
[ 198964-46-4 ]
C₄₅H₅₄O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In tetrahydrofuran at 70℃; for 24h; Inert atmosphere;	A mixture of methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)salicylate [20] (0.21 g, 0.76 mmol), 2,7-dibromo-9,9-dioctyl-9 H-fluorene (0.20 g, 0.34 mmol),Pd(dppf)Cl2 (13 mg, 0.02 mmol) dissolved in THF (5 mL). Asolution of K2CO3 (2.0 M) was added and the mixture washeated up to 70 °C for 24 h. The mixture was extracted withCH2Cl2 (2 × 20 mL). The combined organic phase was washedwith water (2 × 25 mL) and dried over anhydrous Na2SO4. Thesolvent was evaporated and the crude product was purified by asilica column chromatography using hexane:EtOAc (20:1) asan eluent to afford methyl ester of 1 as white solid. The methylester was re-dissolved in THF (2 mL) and MeOH (2 mL) andsaturated KOH aqueous solution (0.1 mL) was added. After themixture was heated to 70 °C for 24 h, the volatile solvents wereevaporated and the residue was dissolved in water (20 mL). Theaqueous layer was acidified by an addition of 6 N HCl and theresulting suspension was centrifuged. The precipitates werecollected and washed with a copious amount of water to afford1 as a yellow solid in 50 % overall yield.

Reference： [1]Khaokeaw, Chenwit; Sukwattanasinitt, Mongkol; Rashatasakhon, Paitoon [Journal of Fluorescence, 2016, vol. 26, # 2, p. 745 - 752]

18
[ 1192152-70-7 ]
[ 1073371-99-9 ]
methyl 4-(5-cyano-2-(trifluoromethyl)-1H-indol-7-yl)-2-hydroxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In water; N,N-dimethyl-formamide at 90℃; for 0.5h; Inert atmosphere;	8.6 Step 6) Synthesis of methyl 4-(5 -cyano-2-(trifluoromethyl)- 1H-indol-7-yl)-2-hydroxyb enzoate 7-Bromo-2-(trifluoromethyl)-1H-indole-5-carbonitrile (340 mg, 1.19 mmol), methyl2-hydroxy-4-(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl) benzoate (300 mg, 1.08 mmol), 1,1 ‘-bi s(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (48 mg,0.059 mmol) and N,N-dimethylformamide (8 mL) were added gradually to a 50 mL two-neck flask. A solution of patassium carbonate (1.1 mL, 2 M) in water was added under nitrogen, then the reaction mixture was stirred for 0.5 h at 90°C. The resulting mixture was cooled to room temperature. To the resulting mixture was added saturated brine (80 mL). The mixture was extracted with ethyl acetate (40 mL x 2). The combined organic phases were washed withsaturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo, then the residue was purified by silica gel chromatography (ethyl acetate/petroleum ether (v/v) = 1/15) to give the title compound as a pale yellow solid (240 mg, 57%).MS (ES-API, pos. ion) m/z: 361.0 [M + 1]t

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2017/36404, 2017, A1 Location in patent: Page/Page column 77; 78

19
[ 1073371-99-9 ]
7-bromo-1-methyl-2-(trifluoromethyl)-1H-indole-5-carbonitrile [ No CAS ]
methyl 4-(5-cyano-1-methyl-2-(trifluoromethyl)-1H-indole-7-yl)-2-hydroxy-benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In water; N,N-dimethyl-formamide at 90℃; for 0.5h; Inert atmosphere;	9.2 Step 2) Synthesis of methyl 4-(5 -cyano- 1 -methyl-2-(trifluoromethyl)- 1H-indole-7-yl)-2-hydroxy-benzoate 7-Bromo- 1 -methyl-2-(trifluoromethyl)- 1H-indole-5-carbonitrile (360 mg, 1.19 mmol), methyl 2-hydroxy-4-(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl) benzoate (300 mg, 1.08 mmol), 1,1 ‘-bi s(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (48 mg,0.059 mmol) and N,N-dimethylformamide (8 mL) were added gradually to a 50 mL two-neck flask. A solution of potassium carbonate (1.1 mL, 2 M) in water was added under nitrogen, then the reaction mixture was stirred for 0.5 h at 90°C. The resulting mixture was cooled to room temperature. To the resulting mixture was added saturated brine (80 mL). The mixture was extracted with ethyl acetate (40 mL x 2). The combined organic phases were washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo, then the residue was purified by silica gel chromatography (ethyl acetate/petroleum ether (v/v)1/15) to give the title compound as a pale yellow solid (140 mg, 32%).MS (ES-API, pos. ion) m/z: 375.1 [M + 1]t

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2017/36404, 2017, A1 Location in patent: Page/Page column 79

20
[ 1073371-99-9 ]
7-bromo-2,3-dihydro-1H-indene-5-carbonitrile [ No CAS ]
methyl 4-(6-cyano-2,3-dihydro-1H-inden-4-yl)-2-hydroxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In N,N-dimethyl-formamide at 90℃; for 0.5h;	11.6 Step 6) Synthesis of methyl 4-(6-cyano-2, 3 -dihydro- 1H-inden-4-yl)-2-hydroxybenzoate 7-Bromo-2, 3 -dihydro- 1H-indene-5 -carbonitrile (320 mg, 1.44 mmol), methyl2-hydroxy-4-(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl) benzoate (360 mg, 1.31 mmol), 1,1 ‘-bi s(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (53 mg,0.065 mmol) and N,N-dimethylformamide (8 mL) were added gradually to a 50 mL two-neck flask. A solution of potassium carbonate (1.3 mL, 2 M) in water was added under nitrogen, then the reaction mixture was stirred for 0.5 h at 90 °C. The resulting mixture was cooled to room temperature. To the resulting mixture was added saturated brine (80 mL). The mixture was extracted with ethyl acetate (40 mL x 2). The combined organic phase was washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo, then the residue was purified by silica gel chromatography (ethyl acetate/petroleum ether (v/v) = 1/20) to give the title compound as a pale yellow solid (238 mg, 62%).MS (ES-API, pos. ion) m/z: 294.1 [M + 1]t

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2017/36404, 2017, A1 Location in patent: Page/Page column 85

21
[ 1073371-99-9 ]
7-bromobenzofuran-5-carbonitrile [ No CAS ]
methyl 4-(5-cyanobenzofuran-7-yl)-2-hydroxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In water; N,N-dimethyl-formamide at 90℃; for 0.5h; Inert atmosphere;	1.6 Synthesis of methyl 4-(5 -cyanobenzofuran-7-yl)-2-hydroxybenzoate 7-Bromobenzofuran-5-carbonitrile (0.32 g, 1.44 mmol), methyl2-hydroxy-4-(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl) benzoate (0.36 g, 1.31 mmol), 1,1 ‘-Bis (diphenylphosphino) ferrocene-palladium (II) dichloride dichloromethane complex (53 mg, 0.065 mmol) and N,N-dimethylformamide (8 mL) were added sequentially to a 50 mL two-neck flask, then a solution of potassium carbonate (1.3 mL, 2 M) in water was added under nitrogen. The reaction mixture was heated to 90°C and stirred for 0.5 h. The resulting mixture was cooled to room temperature, diluted with saturated brine (80 mL), and extracted with ethyl acetate (40 mL x 2). The combined organic phases were washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo, the residue was purified by silica gel chromatography (ethyl acetate/petroleum ether (v/v) = 1/15) to give the title compound as a pale yellow solid (0.29 g, 76%).MS (ES-API, pos. ion) m/z: 294.1 [M + 1]t

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2017/36404, 2017, A1 Location in patent: Paragraph 59; 60

22
[ 1073371-99-9 ]
5-cyano-2-(trifluoromethyl)benzo[b]thiophene-7-yl trifluoromethanesulfonate [ No CAS ]
methyl 4-(5-cyano-2-(trifluoromethyl)benzo[b]thiophene-7-yl)-2-hydroxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In water; N,N-dimethyl-formamide at 90℃; for 5h; Inert atmosphere;	12.9 Step 9) Synthesis of methyl 4-(5 -cyano-2-(trifluoromethyl)benzo[b]thiophene-7-yl)-2-hydroxy benzoate -Cyano-2-(trifluoromethyl)benzo[b]thiophene-7-yltrifluoromethanesulfonate (540 mg,mmol), methyl 2-hydroxy-4-(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl) benzoate (360 mg, 1.31 mmol), 1,1 ‘-bi s(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (53 mg, 0.065 mmol), patassium carbonate (362 mg, 2.62 mmol) and anhydrous 1,4-dioxane (15 mL) were added gradually to a 50 mL two-neck flask. The reaction mixture was stirred for 5 h at 90 °C under nitrogen. The resulting mixture was cooled to room temperature. To the resulting mixture was added saturated brine (80 mL). The mixture was extracted with ethyl acetate (40 mL x 2). The combined organic phases were washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo, the residue was purified by silica gel chromatography (dichloromethane/petroleum ether (v/v) = 1/4) to give the title compound as a white solid (0.336g, 68%).MS (ES-API, pos. ion) m/z: 378.0 [M + 1]t

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2017/36404, 2017, A1 Location in patent: Page/Page column 89

23
[ 496835-91-7 ]
[ 1073371-99-9 ]
methyl 4-(3-cyanonaphthalen-1-yl)-2-hydroxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In water; N,N-dimethyl-formamide at 90℃; for 0.5h; Inert atmosphere;	2.6 Step 6) Synthesis of methyl 4-(3 -cyanonaphthalen- 1 -yl)-2-hydroxyb enzoate 4-Bromo-2-naphthalene carbonitrile (0.417 g, 1.8 mmol), methyl 2-hydroxy-4-(4,4,5,5-tetramethyl -1,3 ,2-dioxaborolan-2-yl)-benzoate (0.42 g, 1.5 mmol), 1,1 ‘-bi s(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (122 mg, 0.15 mmol) and N,N-dimethylformamide (8 mL) were gradually added to a 50 mL two-neck flask. A solution of patassium carbonate (1.5 mL, 2 M) in water was added under nitrogen, then the reaction mixture was stirred for 0.5 h at 90 °C. The resulting mixture was cooled to room temperature and saturated brine (80 mL) was added. The resulting mixture was extracted with ethyl acetate (40 mL x 2). The combined organic phases were washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo, and the residue was purified by silica gel chromatography (dichloromethane/petroleum ether (v/v) = 1/3) to give the title compound as a white solid (0.18 g, 40%).

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2017/36404, 2017, A1 Location in patent: Page/Page column 62

24
[ 1073371-99-9 ]
4-bromo-1-cyclopropyl-2-(trifluoromethyl)-1H-indole-6-carbonitrile [ No CAS ]
methyl 4-(6-cyano-1-cyclopropyl-2-(trifluoromethyl)-1H-indol-4-yl)-2-hydroxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In water; N,N-dimethyl-formamide at 90℃; for 0.5h; Inert atmosphere;	39.2 Step 2) Synthesis of methyl 4-(6-cyano- 1 -cyclopropyl-2-(trifluoromethyl)- 1H-indol-4-yl)-2- hydroxyb enzoate 4-Bromo- 1 -cyclopropyl -2-(trifluoromethyl)- 1H-indole-6-carbonitrile (0.392 g, 1.19 mmol), methyl 2-hydroxy-4-(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl) benzoate (0.300 g, 1.08 mmol), 1,1 ‘-bi s(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (48 mg, 0.059 mmol) and N,N-dimethylformamide (8 mL) were added to a 50 mL two-neck flask. To the reaction mixture was added aqueous potassium carbonate (1.1 mL, 2 M ) under nitrogen protection, and the resulting mixture was stirred at 90 °C for 0.5 h. The reaction mixture was cooled to rt and to the mixture was added saturated brine (80 mL). The resulting mixture was extracted with ethyl acetate (40 mL x 2), and the organic layers were combined. The combined organic layers were washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo. The residue was purified by silica-gel column chromatography (ethyl acetate/petroleum ether (v/v) = 1/15) to give the title compound as a yellow solid (0.337 g, 78%).MS (ES-API, pos. ion) m/z: 401.1 [M+ 1]t

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2017/36404, 2017, A1 Location in patent: Page/Page column 141

25
[ 1073371-99-9 ]
7-bromobenzene[d] [1,3]dioxol-5-carbonitrile [ No CAS ]
methyl 4-(6-cyanobenzo[d][1,3]dioxole-4-yl)-2-hydroxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In water; N,N-dimethyl-formamide at 90℃; for 0.5h; Inert atmosphere;	3.4 Step 4) Synthesis of methyl 4-(6-cyanobenzo[d] [1,3] dioxole-4-yl)-2-hydroxybenzoate 7-Bromobenzene[d] [1,3 ]dioxol-5-carbonitrile (0.30 g, 1.32 mmol), methyl2-hydroxy-4-(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl) benzoate (0.31 g, 1.1 mmol), 1,1 ‘-bi s(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (90 mg,0.11 mmol) and N,N-dimethylformamide (8 mL) were added gradually to a 50 mL two-neck flask. A solution of patassium carbonate (1.1 mL, 2 M) in water was added under nitrogen, then the reaction mixture was stirred for 0.5 h at 90 °C. The resulting mixture was cooled to room temperature, and saturated brine (80 mL) was added. The aqueous phase was extracted with ethyl acetate (40 mL x 2). The combined organic phases were washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (dichloromethane/petroleum ether (v/v) = 1/2) to give the title compound as a white solid (0.16 g, 49%).MS (ES-API, neg. ion) m/z: 296.0 [M - 1].

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2017/36404, 2017, A1 Location in patent: Page/Page column 64

26
[ 1073371-99-9 ]
8-bromoimidazo[1,2-a]pyridin-6-carbonitrile [ No CAS ]
methyl 4-(6-cyanoimidazo[1,2-a]pyridin-8-yl)-2-hydroxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In water; N,N-dimethyl-formamide at 90℃; for 0.5h; Inert atmosphere;	5.4 Step 4) Synthesis of methyl 4-(6-cyanoimidazo[ 1 ,2-a]pyridin-8-yl)-2-hydroxybenzoate 8-Bromoimidazo[1,2-a]pyridin-6-carbonitrile (0.40 g, 1.9 mmol), methyl2-hydroxy-4-(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl) benzoate (0.46 g, 1.7 mmol),1,1 ‘-bi s(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (120 mg,0.16 mmol) and N,N-dimethylformamide (8 mL) were added gradually to a 50 mL two-neck flask.A solution of patassium carbonate (1.7 mL, 2 M) in water was added under nitrogen, then thereaction mixture was stirred for 0.5 h at 90 °C. The resulting mixture was cooled to roomtemperature, diluted with saturated brine (80 mL). The mixture was extracted with ethyl acetate(40 mL x 2). The combined organic phase was washed with saturated brine (60 mL), dried overanhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silicagel chromatography (100% dichloromethane) to give the title compound as a white solid (0.21 g,43%).MS (ES-API, pos. ion) m/z: 294.0 [M + 1]t

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2017/36404, 2017, A1 Location in patent: Page/Page column 68

27
[ 1073371-99-9 ]
4-bromo-2-(trifluoromethyl)-1H-indole-6-carbonitrile [ No CAS ]
methyl 4-(6-cyano-2-(trifluoromethyl)-1H-indol-4-yl)-2-hydroxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In water; N,N-dimethyl-formamide at 90℃; for 0.5h; Inert atmosphere;	37.1 Step 1) Synthesis of methyl 4-(6-cyano-2-(trifluoromethyl)- 1H-indol-4-yl)-2-hydroxyb enzoate 4-Bromo-2-(trifluoromethyl)- 1H-indole-6-carbonitrile (0.344 g, 1.19 mmol), methyl2-hydroxy-4-(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl) benzoate (0.300 g, 1.08 mmol),‘-bi s(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (480.059 mmol) and N,N-dimethylformamide (8 mL) were added to a 50 mL two-neck flask. Toreaction mixture was added aqueous potassium carbonate (1.1 mL, 2 M) under nitrogen, andresulting mixture was stirred at 90 °C for 0.5 h. The reaction mixture was cooled to room temperature and to the mixture was added saturated brine (80 mL). The resulting mixture was extracted with ethyl acetate (40 mL x 2), and the organic layers were combined. The combinedorganic layers were washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo. The residue was purified by silica-gel column chromatography (ethyl acetate/petroleum ether (v/v) = 1/10) to give the title compound as a white solid (0.17 g, 39%).MS (ES-API, pos. ion) m/z: 361.0 [M + 1]t

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2017/36404, 2017, A1 Location in patent: Page/Page column 137; 138

28
[ 1073371-99-9 ]
4-bromo-1-methyl-2-(trifluoromethyl)-1H-indole-6-carbonitrile [ No CAS ]
methyl 4-(6-cyano-1-methyl-2-(trifluoromethyl)-1H-indol-4-yl)-2-hydroxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
17%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In water; N,N-dimethyl-formamide at 90℃; for 0.5h; Inert atmosphere;	6.11 Step 11) Synthesis of methyl 4-(6-cyano- 1 -methyl-2-(trifluoromethyl)- 1H-indol-4-yl)-2- hydroxyb enzoate 4-Bromo-1-methyl-2-(trifluoromethyl)-1H-indole-6-carbonitrile (0.36 g, 1.19 mmol), methyl2-hydroxy-4-(4,4,5, 5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl) benzoate (0.30 g, 1.08 mmol), 1,1 ‘-bi s(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (48 mg,0.059 mmol) and N,N-dimethylformamide (8 mL) were added gradually to a 50 mL two-neck flask. A solution of patassium carbonate (1.1 mL, 2 M) in water was added under nitrogen, then the reaction mixture was stirred for 0.5 h at 90 °C. The resulting mixture was cooled to room temperature, diluted with saturated brine (80 mL). The mixture was extracted with ethyl acetate (40 mL x 2). The combined organic phases were washed with saturated brine (60 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/petroleum ether (v/v) = 1/15) to give the title compound as a pale yellow solid (70 mg, 17%).MS (ES-API, pos. ion) m/z: 375.2 [M + 1]t

Reference： [1]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - WO2017/36404, 2017, A1 Location in patent: Page/Page column 72

29
[ 1073371-99-9 ]
1H-indole-1-carboxylic acid, 3-[[(7S,10S,13S)-17-bromo-20-chloro-10-[4-[[(1,1-dimethylethoxy)carbonyl]amino]butyl]-7-[3-[[(1,1-dimethylethoxy)carbonyl]amino]propyl]-5,6,7,8,9,10,11,12,13,14,15,16-dodecahydro-12-methyl-8,11,14-trioxopyrido[2,3-b][1,5,8,11,14]benzothiatetraazacycloheptadecin-13-yl]methyl]-, 1,1-dimethylethyl ester [ No CAS ]
tert-butyl 3-(((7S,10S,13S)-10-(4-((tert-butoxycarbonyl)amino)butyl)-7-(3-((tert-butoxycarbonyl)amino)propyl)-20-chloro-17-(3-hydroxy-4-(methoxycarbonyl)phenyl)-12-methyl-8,11,14-trioxo-5,6,7,8,9,10,11,12,13,14,15,16-dodecahydrobenzo[b]pyrido[3,2-p][1,5,8,11,14]thiatetraazacycloheptadecin-13-yl)methyl)-1H-indole-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 100℃; for 1.5h; Sealed tube; Microwave irradiation; Inert atmosphere;	3.1 Step 1: Tert-Butyl 3-(((7S,10S,13S)-10-(4-((tert-butoxycarbonyl)amino)butyl)-7-(3-((tert-butoxycarbonyl)amino)propyl)-20-chloro-17-(3-hydroxy-4-(methoxycarbonyl)phenyl)-12-methyl-8,11,14-trioxo-5,6,7,8,9,10,11,12,13,14,15,16-dodecahydrobenzo[b]pyrido[3,2-p][1,5,8,11,14]thiatetraazacycloheptadecin-13-yl)methyl)-1H-indole-1-carboxylate tert-Butyl 3-(((7S,10S,13S)-17-bromo-10-(4-((tert-butoxycarbonyl)amino)butyl)-7-(3-((tert-butoxycarbonyl)amino)propyl)-20-chloro-12-methyl-8,11,14-trioxo-5,6,7,8,9,10,11,12,13,14,15,16-dodecahydrobenzo[b]pyrido[3,2-p][1,5,8,11,14]thiatetraazacycloheptadecin-13-yl)methyl)-1H-indole-1-carboxylate (CAS-RN 2097294-18-1; 250 mg, 0.23 mmol) was dissolved in 1,4-dioxane (6 mL) and water (1 mL), then methyl 2-hydroxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (CAS-RN 1073371-99-9; 256 mg, 922 μmol) and potassium carbonate (95 mg, 0.69 mmol) were added. The reaction mixture was sparged with argon for 2 min while sonicating the vessel in an ultrasonic bath. Then 1,1'-bis(diphenylphosphino)ferrocene dichloropalladium(II) (51.3 mg, 69.2 μmol) was added, and degassing continued for another 2 min. The tube was then sealed and heated at 100° C. under microwave irradiation for 90 min, then the reaction mixture was partitioned between water and ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, and evaporated. The crude product was purified by chromatography (silica gel; heptane-(ethyl acetate/methanol 9:1) gradient) to produce the title compound (160 mg, 60%) as a white solid.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2019/321440, 2019, A1 Location in patent: Paragraph 0315

30
[ 1073371-99-9 ]
methyl 7,10-dioxa-13,17,18,21-tetraazatetracyclo[12.5.2.1²,⁶.0¹₇,²₀]docosa-1⁽²⁰⁾,2,4,6⁽²²⁾,14⁽²¹⁾,15,18-heptaene-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C / Inert atmosphere 4: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C
	Multi-step reaction with 4 steps 1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C

Reference： [1]Berger, Benedict-Tilman; Celik, Ibrahim Ethem; Greco, Francesco Aleksy; Hanke, Thomas; Knapp, Stefan; Krämer, Andreas; Kurz, Christian Georg; Tjaden, Amelie [European Journal of Medicinal Chemistry, 2020, vol. 208]
[2]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

31
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-benzyl-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C / Inert atmosphere 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride / dichloromethane / 1 h / 20 °C 6.2: 16 h / 20 °C
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Berger, Benedict-Tilman; Celik, Ibrahim Ethem; Greco, Francesco Aleksy; Hanke, Thomas; Knapp, Stefan; Krämer, Andreas; Kurz, Christian Georg; Tjaden, Amelie [European Journal of Medicinal Chemistry, 2020, vol. 208]
[2]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

32
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-(2,4-dichlorobenzyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

33
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-(4-chloro-2-fluorobenzyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

34
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-(4-chloro-2-methylbenzyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

35
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-(3,5-dichlorobenzyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

36
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-(3-chloro-5-fluorobenzyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

37
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-(2,3-dichlorobenzyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

38
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-(3-chloro-2-fluorobenzyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

39
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-(naphthalen-1-ylmethyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

40
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-(1-phenylethyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

41
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-((S)-1-phenylethyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

42
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-((R)-1-phenylethyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

43
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-(1-(naphthalen-1-yl)ethyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

44
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-(pyridin-3-ylmethyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

45
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-(pyridin-4-ylmethyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

46
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-((R)-1-(pyridin-4-yl)ethyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

47
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-((S)-1-(pyridin-4-yl)ethyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

48
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-(quinolin-4-ylmethyl)-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

49
[ 1073371-99-9 ]
CK₁₈₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

50
[ 1073371-99-9 ]
(1³Z,1⁴E)-N-methyl-3,6-dioxa-9-aza-1(3,5)-pyrazolo[1,5-a]pyrimidina-2(1,3)-benzenacyclononaphane-2⁴-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl [2’,4’,6’-tris(propan-2-yl)-[1,1‘-biphenyl]-2-yl]phosphane; tripotassium phosphate tribasic / 1,4-dioxane; lithium hydroxide monohydrate / 0.67 h / 110 °C 2.1: N,N,N-tributylbutan-1-aminium fluoride / tetrahydrofuran / 3 h / 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine; Sodium sulfate [anhydrous] / toluene; 2-methyltetrahydrofuran / 3 h / 90 °C 4.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C 5.1: lithium hydroxyde monohydrate / tetrahydrofuran; lithium hydroxide monohydrate / 16 h / 50 °C 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 6.2: 18 h / 20 °C / Inert atmosphere

Reference： [1]Kurz, Christian G.; Preuss, Franziska; Tjaden, Amelie; Cusack, Martin; Amrhein, Jennifer Alisa; Chatterjee, Deep; Mathea, Sebastian; Berger, Lena Marie; Berger, Benedict-Tilman; Krämer, Andreas; Weller, Michael; Weiss, Tobias; Müller, Susanne; Knapp, Stefan; Hanke, Thomas [Journal of Medicinal Chemistry, 2022, vol. 65, # 11, p. 7799 - 7817]

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CAS No. :	1073371-99-9	MDL No. :	MFCD08458200
Formula :	C₁₄H₁₉BO₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SRYGMLVCVMGUTB-UHFFFAOYSA-N
M.W :	278.11	Pubchem ID :	17998928
Synonyms :

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

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 1073371-99-9 ] {[proInfo.proName]}

Quality Control of [ 1073371-99-9 ]

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[ 1073371-99-9 ] Synthesis Path-Downstream 1~50

Related Functional Groups of
[ 1073371-99-9 ]

Organoboron

Aryls

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

[ CAS No. 1073371-99-9 ] {[proInfo.proName]}

Quality Control of [ 1073371-99-9 ]

Related Doc. of [ 1073371-99-9 ]

Product Details of [ 1073371-99-9 ]

Safety of [ 1073371-99-9 ]

Application In Synthesis of [ 1073371-99-9 ]

[ 1073371-99-9 ] Synthesis Path-Downstream 1~50

Related Functional Groups of [ 1073371-99-9 ]

Organoboron

Aryls

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 1073371-99-9 ]