Name: 914610-39-2|1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine|96%
Brand: Ambeed
SKU: A727022
Price: 30.0 USD
Availability: InStock
Rating: 99 (26 reviews)

1
[ 837-12-7 ]
[ 73183-34-3 ]
[ 914610-39-2 ]

Yield	Reaction Conditions	Operation in experiment
65%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In toluene;Inert atmosphere; Reflux;	l-Methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl]plperazlne (955-2)Pd(PPh3)* (3 g) was added to a mixture of l-(4-bromophenyl sulfonyl)-4-methylpiperazine (20 g, 62.6 mmol), plnacolatodlboron (11 g, 62.6 mmol), and potassium carbonate (17.8 g, 0.13 mol) In toluene (1 L) under nitrogen protection. The mixture was heated under reflux overnight. After cooling to room temperature, the solvent was removed under vacuum. To the residue were added water (500 ml) and ethyl acetate (500 ml). The organic phase was collected, and the water phase was extracted with ethyl acetate (500 ml x2). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to afford 1- methyl-4-[4- (4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl]piperazlne (955-2, 15.1 g, yield 65%). LC-MS: 367.2 (M+l).
65%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; for 12h;Inert atmosphere; Reflux;	To a mixture of 1-(4-bromophenyl sulfonyl)-4-methylpiperazine (1) (20g, 62.6mmol), pinacolatodiboron (11g, 62.6mmol), and potassium carbonate (17.8g, 0.13mol) in toluene Pd(PPh3)4 (3g) was added (1 L) under nitrogen protection. The mixture was heated under reflux overnight. After cooling to RT, the solvent was removed under vacuum. To the residue were added water (500mL) and EA (500mL). The organic phase was collected, and the water phase was extracted with EA (500mL×2). The organic phases were combined, dried over anhydrous sodium sulfate and concentrated to afford 2 (15.1g, yield 65%). LC-MS: 367.2 (M+l).
	With 1,1'-bis-(diphenylphosphino)ferrocene; potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 90℃; for 8h;Heating;	1. 2-R2-(4-METHOXVPYRIDIN-2-VL) ETHVLL-6-S-(4-METHYLPIDERAZIN-1-YL-SULFONVL) PHENYLLTH-IMIDAZO- [45-BLPYRIDINE A mixture of 1.12 g of 1- (4-BROMO-BENZENE-SULFONYL)-4-METHYL-PIPERAZINE, 0.978 g of bis- (pinacolato)- diboron, 0.06 g OF 1, 1 -BIS- (DIPHENYLPHOSPHINO)-FERROCENE, 0.077 g of [1,1'-bis (diphenyl- phosphino) ferrocene] palladium-dichloride (complex with CH2CI2), 1.03 g of potassium acetate in 40 ML of degassed dioxane are heated to 90C under N2 FOR 8 hours. To the resulting mixture 15 ml of degassed dioxane, 0.931 g of 2- [2- (4-methoxypyridin-2-yl) ethyl]-6-iodo-3H-imidazo [4,5-b] pyridine (starting material A1), 0.283 g OF TETRAKIS (TRIPHENYLPHOSPHINE)-PALLADIUM (0) and a solution of 0.678 G of potassium carbonate and 0.208 g of lithium chloride in 15 ml of degassed water are added under N2. The mixture is heated to reflux under N2 for 16 hours and, after cooling, addition of water and adjusting the pH to 7, it is extracted three times with DICHLOROMETHANE. The combined organic phases are dried over sodium sulfate, concentrated and the residue is chromatographed on a silica gel column (DICHLOROMETHANELMETHANOL 15-10: 1). Concentration of the chromatographically pure fractions and crystallization of the residue from ETHYLACETATE gives 0.545 g of the title compound as a solid of m. p. 193-195C. The mass spectrum shows the molecular peak MHS at 493.4 Da.

Reference： [1]Patent: WO2012/130299,2012,A1 .Location in patent: Page/Page column 120
[2]Journal of Medicinal Chemistry,2013,vol. 56,p. 3820 - 3832
[3]Journal of Medicinal Chemistry,2015,vol. 58,p. 5522 - 5537
[4]Biochemical Pharmacology,2019,vol. 164,p. 349 - 367
[5]Journal of Heterocyclic Chemistry,2019,vol. 56,p. 1260 - 1274
[6]Patent: WO2005/30770,2005,A1 .Location in patent: Page/Page column 21
[7]Journal of Medicinal Chemistry,2022,vol. 65,p. 1265 - 1282

2
[ 914610-39-2 ]
[ 608880-54-2 ]
2-[2-(4-methoxypyridin-2-yl)ethyl]-6-[4-(4-methylpiperazin-1-yl-sulfonyl)phenyl]-3H-imidazo-[4,5-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; lithium chloride In 1,4-dioxane; water for 16h; Heating / reflux;	1 1. 2-R2-(4-METHOXVPYRIDIN-2-VL) ETHVLL-6-S-(4-METHYLPIDERAZIN-1-YL-SULFONVL) PHENYLLTH-IMIDAZO- [45-BLPYRIDINE A mixture of 1.12 g of 1- (4-BROMO-BENZENE-SULFONYL)-4-METHYL-PIPERAZINE, 0.978 g of bis- (pinacolato)- diboron, 0.06 g OF 1, 1 -BIS- (DIPHENYLPHOSPHINO)-FERROCENE, 0.077 g of [1,1'-bis (diphenyl- phosphino) ferrocene] palladium-dichloride (complex with CH2CI2), 1.03 g of potassium acetate in 40 ML of degassed dioxane are heated to 90°C under N2 FOR 8 hours. To the resulting mixture 15 ml of degassed dioxane, 0.931 g of 2- [2- (4-methoxypyridin-2-yl) ethyl]-6-iodo-3H-imidazo [4,5-b] pyridine (starting material A1), 0.283 g OF TETRAKIS (TRIPHENYLPHOSPHINE)-PALLADIUM (0) and a solution of 0.678 G of potassium carbonate and 0.208 g of lithium chloride in 15 ml of degassed water are added under N2. The mixture is heated to reflux under N2 for 16 hours and, after cooling, addition of water and adjusting the pH to 7, it is extracted three times with DICHLOROMETHANE. The combined organic phases are dried over sodium sulfate, concentrated and the residue is chromatographed on a silica gel column (DICHLOROMETHANELMETHANOL 15-10: 1). Concentration of the chromatographically pure fractions and crystallization of the residue from ETHYLACETATE gives 0.545 g of the title compound as a solid of m. p. 193-195°C. The mass spectrum shows the molecular peak MHS at 493.4 Da.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2005/30770, 2005, A1 Location in patent: Page/Page column 21

3
[ 914610-38-1 ]
[ 73183-34-3 ]
[ 914610-39-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate In N,N-dimethyl-formamide at 85℃; for 2.5h;	9.B 5.4 g of the compound obtained in Step A (14.75 mmol), 4.52 g of bis(pinacolato)diborane (19.18 mmol), 4.34 g of potassium acetate (44.25 mmol) and 50 ml of dimethylformamide are introduced into a 100 ml two-necked flask. The reaction mixture is degassed by bubbling a current of nitrogen through for 30 minutes; 165 mg of palladium acetate (0.737 mmol) are then added. The reaction mixture is stirred under a gentle current of nitrogen for 2 hours 30 minutes at 85° C. After cooling to ambient temperature, the reaction mixture is diluted with water and extracted with CH2Cl2. The organic phases are collected, washed with brine, dried and evaporated under reduced pressure. The residue obtained is chromatographed on SiO2 (CH2Cl2/ MeOH 95/5) to yield the title product in the form of a creamy-white solid. Melting point: 126-136° C.

Reference： [1]Current Patent Assignee: SERVIER MONDE - US2006/258670, 2006, A1 Location in patent: Page/Page column 6

4
[ 837-12-7 ]
[ 914610-39-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate; bis(pinacol)diborane;1,1'-bis-(diphenylphosphino)ferrocene; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 90℃; for 24h;	1. 1-(2-lmidazol-1-yl-pyrimidin-5-yl)-1-[4'-(4-methyl-piperazine-1-sulfonyl)-biphenyl-4-yl]- methanone; 492 mg of 1-(4-Bromo-benzenesulfonyl)-4-methyl-piperazine (compound A1 ) are dissolved in 7 ml of oxygen-free dioxane under an atmosphere of dry nitrogen. Subsequently, 429 mg of bis(pinacolato)- diboron, 34 mg of Pd(CI)2(dppf) ' CH2CI2, 26 mg of DPPF (1 ,1'- bis(diphenylphosphino)-ferrocene), and 453 mg of potassium acetate are added. The reaction mixture is heated at 9O0C for 24 hours during which time the former yellowish suspension becomes black (LC-MS monitoring for formation of boronic ester intermediate). Thereafter, 329 mg of 1-(4-bromo-phenyl)-1-(2-imidazol-1-yl-pyrimidin-5-yl)- methanone (compound B1 ), 276 mg of potassium carbonate, 85 mg of lithium chloride, 1 16 mg of Pd(PPh3)4, 11 ml of oxygen-free dioxane, and 11 ml of water are added. The reaction mixture is heated at 9O0C and stirring is continued for 16 hours. Subsequently, the suspension is concentrated in vacuo and co-evaporated twice with 20 ml each of toluene. The resulting crude material is purified by chromatography (eluent: dichloromethane/ethanol 20:1 parts per volume) to afford 165 mg of the title compound as a colorless solid. M. p. 2520C. ESI-MS: 489.3 (MH+). TLC: Rf = 0.56 (dichloromethane/methanol 10:1 parts per volume).

Reference： [1]Patent: WO2007/39581,2007,A1 .Location in patent: Page/Page column 26

5
[ 914610-39-2 ]
[ 933043-51-7 ]
1-(2-imidazol-1-yl-pyrimidin-5-yl)-1-[4'-(4-methyl-piperazine-1-sulfonyl)-biphenyl-4-yl]-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; lithium chloride In 1,4-dioxane; water at 90℃; for 16h;	1 1. 1-(2-lmidazol-1-yl-pyrimidin-5-yl)-1-[4'-(4-methyl-piperazine-1-sulfonyl)-biphenyl-4-yl]- methanone; 492 mg of 1-(4-Bromo-benzenesulfonyl)-4-methyl-piperazine (compound A1 ) are dissolved in 7 ml of oxygen-free dioxane under an atmosphere of dry nitrogen. Subsequently, 429 mg of bis(pinacolato)- diboron, 34 mg of Pd(CI)2(dppf) ' CH2CI2, 26 mg of DPPF (1 ,1'- bis(diphenylphosphino)-ferrocene), and 453 mg of potassium acetate are added. The reaction mixture is heated at 9O0C for 24 hours during which time the former yellowish suspension becomes black (LC-MS monitoring for formation of boronic ester intermediate). Thereafter, 329 mg of 1-(4-bromo-phenyl)-1-(2-imidazol-1-yl-pyrimidin-5-yl)- methanone (compound B1 ), 276 mg of potassium carbonate, 85 mg of lithium chloride, 1 16 mg of Pd(PPh3)4, 11 ml of oxygen-free dioxane, and 11 ml of water are added. The reaction mixture is heated at 9O0C and stirring is continued for 16 hours. Subsequently, the suspension is concentrated in vacuo and co-evaporated twice with 20 ml each of toluene. The resulting crude material is purified by chromatography (eluent: dichloromethane/ethanol 20:1 parts per volume) to afford 165 mg of the title compound as a colorless solid. M. p. 2520C. ESI-MS: 489.3 (MH+). TLC: Rf = 0.56 (dichloromethane/methanol 10:1 parts per volume).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2007/39581, 2007, A1 Location in patent: Page/Page column 26

6
[ 914610-39-2 ]
[ 1254318-91-6 ]
[ 1254319-49-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate In water; acetonitrile at 85℃; for 18h; Inert atmosphere of nitrogen;	29.i (S)-tert-Buty 4-( 1 -amino-3 -(4-iodophenyl)- 1 -oxopropan-2-ylcarbamoyl)tetrahydro-2H- pyran-4-ylcarbamate (Example 1, step (iii), 250mg) and l-methyl-4-(4-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)phenylsulfonyl)piperazine (177 mg) in acetonitrile (8 mL) was treated with aqueous sodium carbonate solution (2M, 0.483 mL) and then nitrogen was bubbled through the mixture. 1 , 1 bis(Di-fert-butylphosphino)ferrocene palladium dichloride (5 mg) was added and the mixture was heated at 85°C under nitrogen for 18 h. The mixture was purified by chromatography on silica eluting with ethyl acetate / ohexane (70:10 to 100:0), then methanol / ethyl acetate (5:95) and then methanol / ethyl acetate / triethylamine (5 : 95 : 1) to afford the sub-titled compound (267 mg).m/e (MultiMode-) 629 [M-H]"

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2010/128324, 2010, A1 Location in patent: Page/Page column 114-115

7
[ 914610-39-2 ]
[ 1398718-40-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium carbonate / palladium bis[bis(diphenylphosphino)ferrocene] dichloride / N,N-dimethyl-formamide; water / 80 °C / Inert atmosphere 2: 1,3,5-trichloro-2,4,6-triazine / N,N-dimethyl-formamide / 4 h / 20 °C

Reference： [1]Current Patent Assignee: PROZYMEX AS; LAURITZEN CONNI - WO2012/119941, 2012, A1

8
[ 914610-39-2 ]
[ 1398718-42-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sodium carbonate / palladium bis[bis(diphenylphosphino)ferrocene] dichloride / N,N-dimethyl-formamide; water / 80 °C / Inert atmosphere 2: 1,3,5-trichloro-2,4,6-triazine / N,N-dimethyl-formamide / 4 h / 20 °C 3: formic acid / 4 h / 20 °C 4: 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride / dichloromethane / 0 - 20 °C

Reference： [1]Current Patent Assignee: PROZYMEX AS; LAURITZEN CONNI - WO2012/119941, 2012, A1

9
[ 914610-39-2 ]
[ 1398718-44-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium carbonate / palladium bis[bis(diphenylphosphino)ferrocene] dichloride / N,N-dimethyl-formamide; water / 80 °C / Inert atmosphere 2: 1,3,5-trichloro-2,4,6-triazine / N,N-dimethyl-formamide / 4 h / 20 °C 3: formic acid / 4 h / 20 °C

Reference： [1]Current Patent Assignee: PROZYMEX AS; LAURITZEN CONNI - WO2012/119941, 2012, A1

10
[ 914610-39-2 ]
[ 1398718-47-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sodium carbonate / palladium bis[bis(diphenylphosphino)ferrocene] dichloride / N,N-dimethyl-formamide; water / 80 °C / Inert atmosphere 2: 1,3,5-trichloro-2,4,6-triazine / N,N-dimethyl-formamide / 4 h / 20 °C 3: formic acid / 4 h / 20 °C 4: 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride / dichloromethane / 0 - 20 °C

Reference： [1]Current Patent Assignee: PROZYMEX AS; LAURITZEN CONNI - WO2012/119941, 2012, A1

11
[ 914610-39-2 ]
[ 1398717-83-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: sodium carbonate / palladium bis[bis(diphenylphosphino)ferrocene] dichloride / N,N-dimethyl-formamide; water / 80 °C / Inert atmosphere 2: 1,3,5-trichloro-2,4,6-triazine / N,N-dimethyl-formamide / 4 h / 20 °C 3: formic acid / 4 h / 20 °C 4: 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride / dichloromethane / 0 - 20 °C 5: piperidine / dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: PROZYMEX AS; LAURITZEN CONNI - WO2012/119941, 2012, A1

12
[ 914610-39-2 ]
[ 1398717-85-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: sodium carbonate / palladium bis[bis(diphenylphosphino)ferrocene] dichloride / N,N-dimethyl-formamide; water / 80 °C / Inert atmosphere 2: 1,3,5-trichloro-2,4,6-triazine / N,N-dimethyl-formamide / 4 h / 20 °C 3: formic acid / 4 h / 20 °C 4: 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride / dichloromethane / 0 - 20 °C 5: piperidine / dichloromethane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: PROZYMEX AS; LAURITZEN CONNI - WO2012/119941, 2012, A1

13
[ 914610-39-2 ]
tert-butyl (S)-[1-amino-3-(4-bromophenyl)-1-oxopropan-2-yl]carbamate [ No CAS ]
[ 1398718-38-1 ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium carbonate In water; N,N-dimethyl-formamide at 80℃; Inert atmosphere;	2 (S)-tert-Butyl l-amino-3-(4'-(4-methylpiperazin-l-ylsulfonyl)biphenyl-4-yl)-l- oxopropan-2-ylcarbamate (PZ1018-1): A mixture of PZ1024-3 (3.0 g, 8.8 mmol), 1- methyl-4-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)prienylsulfonyl)- piperazine (3.6 g, 9.7 mmol) and aqueous Na2C03 solution (2.0 M, 14.2 mL, 28.4 mmol) in DMF (50 mL) was purged with nitrogen three times and PdCI2(dppf)2 (0.3 g, 0.41 mmol) was added. The mixture was stirred at 80°C overnight. After the mixture was cooled to room temperature, water (150 mL) and ethyl acetate (150 mL) were added. The organic phase was separated and the aqueous phase was extracted with ethyl acetate (150 mL x 2). The combined organic phases were dried over anhydrous Na2S04 and concentrated. The residue was purified by flash column chromatography on silica gel (EA/MeOH = 20: 1) to give PZ1018-1 (3.3 g, 82% yield). LC-MS: 503 [M + H]+.

Reference： [1]Current Patent Assignee: PROZYMEX AS; LAURITZEN CONNI - WO2012/119941, 2012, A1 Location in patent: Page/Page column 120-121

14
[ 914610-39-2 ]
[ 1092460-42-8 ]
(1S,2S)-methyl 1-(tert-butoxycarbonylamino)-2-[4'-(4-methyl-piperazine-1-yl-sulfonyl)biphenyl-4-yl]cyclopropanecarboxylate [ No CAS ]
(1R,2R)-methyl 1-(tert-butoxycarbonylamino)-2-[4'-(4-methyl-piperazine-1-yl-sulfonyl)biphenyl-4-yl]cyclopropanecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate In 1,4-dioxane; water Inert atmosphere; Reflux;	5 (1R, 2R)- (IS, 2S)-Methyl l-(tert-butoxycart>onylamlno)-2-[4,-(4-methyl-piperazln-1-yl- suffonyl)blphenyl-4-yl]cydopropanecarboxylate (955-3)PdCI2(dppf)2 (2 g) was added to a mixture of 955-2 (15 g, 40.9 mol), compound 3 (15.1 g, 40.9 mmol), and sodium carbonate aqueous solution (8.67 g, 2 M) In 1,4-dioxane (1 L) under nitrogen protection. The mixture was refluxed overnight. After cooling to room temperature, the solvent was removed under vacuum. To the residue were added water (500 ml) and ethyl acetate (500 ml). The organic phase was collected, and the water phase was extracted with ethyl acetate (500 ml x2). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by HPFC (ethyl acetate/petroleum ether as eluent) to afford the (1R, 2R)- and (IS, 2S)- mixture 955-3 (12.9 g, yield 60%). LC- MS: 530.2 ( +l).

Reference： [1]Current Patent Assignee: PROZYMEX AS - WO2012/130299, 2012, A1 Location in patent: Page/Page column 120-121

15
[ 914610-39-2 ]
[ 1464153-49-8 ]
[ 1464150-75-1 ]

Yield	Reaction Conditions	Operation in experiment
36%	With potassium phosphate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ In 1,4-dioxane; water at 20℃; for 6h; Inert atmosphere; Reflux;	40 Example 40: 4-(6-(4-(4-methylpiperazin-l -ylsulfonyl phenyl)imidazo[ 1 ,2-alpyrazin-3- yPbenzonitrile l-methyl-4-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenylsulfonyl)piperazine (240 mg, 0.656 mmol), K3P04 (212 mg, 1 mmol) and Pd(PPh3)4 (28 mg, 0.025 mmol) were added sequentially to a solution of 4-(6-bromoimidazo[ 1 ,2-a]pyrazin-3-yl)benzonitrile (150 mg, 0.5 mmol) in a mixture of l,4-dioxane/H20 (10: 1 mL) at room temperature under argon atmosphere. The reaction mixture was refluxed for 6 h and was diluted with water (10 mL) and extracted with EtOAc (3X50 mL). The combined organic layer was dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, eluent CHCl3/MeOH 95:5) to afford 4-(6-(4-(4-methylpiperazin- l-ylsulfonyl)phenyl)imidazo[l,2-a]pyrazin-3-yl)benzonitrile (80 mg, 36%, AUC HPLC 99.1%) as an off-white solid; m.p. 220-228°C. 1H NMR (400 MHz, CDC13) δ (ppm): 9.30 (s, 1 H), 8.61 (s, 1 H), 8.08 (d, J= 8.8 Hz, 2 H), 8.00 (s, 1 H), 7.92-7.85 (m, 4 H), 7.77 (d, J = 8.4 Hz, 2 H), 3.08 (bs, 4 H), 2.50-2.48 (m, 4 H), 2.27 (s, 3 H); MS (ESI) m/z 459.27 [C24H22N602S + H]+.
36%	With potassium phosphate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ In 1,4-dioxane; water for 6h; Inert atmosphere; Reflux;	40 Example 40 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl)piperazine (240 mg, 0.656 mmol), K3PO4 (212 mg, 1 mmol) and Pd(PPh3)4 (28 mg, 0.025 mmol) were added sequentially to a solution of 4-(6-bromoimidazo[1,2-a]pyrazin-3-yl)benzonitrile (150 mg, 0.5 mmol) in a mixture of 1,4-dioxane/H2O (10:1 mL) at room temperature under argon atmosphere. The reaction mixture was refluxed for 6 h and was diluted with water (10 mL) and extracted with EtOAc (3*50 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, eluent CHCl3/MeOH 95:5) to afford 4-(6-(4-(4-methylpiperazin-1-ylsulfonyl)phenyl)imidazo[1,2-a]pyrazin-3-yl)benzonitrile (80 mg, 36%, AUC HPLC 99.1%) as an off-white solid; m.p. 220-228° C. 1H NMR (400 MHz, CDCl3) δ (ppm): 9.30 (s, 1H), 8.61 (s, 1H), 8.08 (d, J=8.8 Hz, 2H), 8.00 (s, 1H), 7.92-7.85 (m, 4H), 7.77 (d, J=8.4 Hz, 2H), 3.08 (bs, 4H), 2.50-2.48 (m, 4H), 2.27 (s, 3H); MS (ESI) m/z 459.27 [C24H22N6O2S+H]+.

Reference： [1]Current Patent Assignee: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH - WO2013/147711, 2013, A1 Location in patent: Page/Page column 120
[2]Current Patent Assignee: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH - US2014/371199, 2014, A1 Location in patent: Paragraph 0463

16
[ 914610-39-2 ]
[ 552294-86-7 ]
N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)thieno[3,2-d]pyrimidin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In ethanol; water at 85℃; for 12h;

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]

17
[ 98-58-8 ]
[ 914610-39-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrahydrofuran / 20 °C 2: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane
	Multi-step reaction with 2 steps 1: tetrahydrofuran / 4 h / 20 °C / Inert atmosphere 2: potassium acetate; palladium bis[bis(diphenylphosphino)ferrocene] dichloride / 1,4-dioxane; dimethyl sulfoxide / 16 h / 100 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: tetrahydrofuran / 16 h / 20 °C 2: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 3 h / 100 °C / Inert atmosphere

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]
[2]Kaoukabi, Asma; Belachemi, Larbi; Lahcini, Mohammed; Massuard, Marie-Claude Viaud; Croix, Cécile [Journal of Heterocyclic Chemistry, 2019, vol. 56, # 4, p. 1260 - 1274]
[3]Baumann, Georg; Meckel, Tobias; Böhm, Kevin; Shih, Yung-Hsin; Dickhaut, Mirco; Reichardt, Torben; Pilakowski, Johannes; Pehl, Ulrich; Schmidt, Boris [Journal of Medicinal Chemistry, 2022, vol. 65, # 2, p. 1265 - 1282]

18
[ 109-01-3 ]
[ 914610-39-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrahydrofuran / 20 °C 2: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane
	Multi-step reaction with 2 steps 1: tetrahydrofuran / 4 h / 20 °C / Inert atmosphere 2: potassium acetate; palladium bis[bis(diphenylphosphino)ferrocene] dichloride / 1,4-dioxane; dimethyl sulfoxide / 16 h / 100 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: tetrahydrofuran / 16 h / 20 °C 2: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 3 h / 100 °C / Inert atmosphere

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]
[2]Kaoukabi, Asma; Belachemi, Larbi; Lahcini, Mohammed; Massuard, Marie-Claude Viaud; Croix, Cécile [Journal of Heterocyclic Chemistry, 2019, vol. 56, # 4, p. 1260 - 1274]
[3]Baumann, Georg; Meckel, Tobias; Böhm, Kevin; Shih, Yung-Hsin; Dickhaut, Mirco; Reichardt, Torben; Pilakowski, Johannes; Pehl, Ulrich; Schmidt, Boris [Journal of Medicinal Chemistry, 2022, vol. 65, # 2, p. 1265 - 1282]

19
[ 914610-39-2 ]
6-bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)quinolin-4-amine [ No CAS ]
N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)quinolin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With palladium diacetate; triethylamine In ethanol; water at 120℃; for 1h; Microwave irradiation;

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]

20
[ 914610-39-2 ]
7-bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)quinolin-4-amine [ No CAS ]
N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-7-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)quinolin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	With palladium diacetate; triethylamine In ethanol; water at 120℃; for 1h; Microwave irradiation;

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]

21
[ 914610-39-2 ]
7-Bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)isoquinolin-1-amine [ No CAS ]
N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-7-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)isoquinolin-1-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With palladium diacetate; triethylamine In ethanol; water at 120℃; for 1h; Microwave irradiation;

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]

22
[ 914610-39-2 ]
6-Bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)isoquinolin-1-amine [ No CAS ]
N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)isoquinolin-1-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With palladium diacetate; triethylamine In ethanol; water at 120℃; for 1h; Microwave irradiation;

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]

23
[ 914610-39-2 ]
6-Bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)cinnolin-4-amine [ No CAS ]
N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)cinnolin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	With palladium diacetate; triethylamine In ethanol; water at 120℃; for 1h; Microwave irradiation;

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]

24
[ 914610-39-2 ]
7-Bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)cinnolin-4-amine [ No CAS ]
N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-7-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)cinnolin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With bis-triphenylphosphine-palladium(II) chloride; triethylamine In ethanol; water at 120℃; for 1h; Microwave irradiation;

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]

25
[ 914610-39-2 ]
7-Bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)phthalazin-1-amine [ No CAS ]
N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-7-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)phthalazin-1-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With bis-triphenylphosphine-palladium(II) chloride; triethylamine In ethanol; water at 120℃; for 1h; Microwave irradiation;

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]

26
[ 914610-39-2 ]
6-bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)phthalazin-1-amine [ No CAS ]
N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)phthalazin-1-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With bis-triphenylphosphine-palladium(II) chloride; triethylamine In ethanol; water at 120℃; for 1h; Microwave irradiation;

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]

27
[ 914610-39-2 ]
4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-iodoquinoline-3-carbonitrile [ No CAS ]
4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)quinoline-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In ethanol; water at 85℃; for 7h; Inert atmosphere;

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]

28
[ 914610-39-2 ]
4-((4-(benzyloxy)-3-chlorophenyl)amino)-6-iodoquinoline-3-carbonitrile [ No CAS ]
4-((4-(benzyloxy)-3-chlorophenyl)amino)-6-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)quinoline-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In ethanol; water at 85℃; for 7h; Inert atmosphere;

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]

29
[ 914610-39-2 ]
[ 552295-33-7 ]
N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)thieno[3,2-d]pyrimidin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In ethanol; water at 85℃; for 12h;

Reference： [1]Devine, William; Woodring, Jennifer L.; Swaminathan, Uma; Amata, Emanuele; Patel, Gautam; Erath, Jessey; Roncal, Norma E.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. [Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537]

30
[ 837-12-7 ]
[ 73183-34-3 ]
[ 914610-39-2 ]
C₂₂H₃₀N₄O₄S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate; palladium diacetate; In N,N-dimethyl-formamide; at 80℃; for 4h;Inert atmosphere;	A 50 mL round bottom flask was charged with 1-(4-bromophenylsulfonyl)-4-methylpiperazine (110 mg, 0.350 mmol), bis-(pinacolato)-diboron (93 mg, 0.37 mmol), palladium acetate (6 mg, 0.02 mmol), and potassium acetate (103 mg, 1.05 mmol) in N,N-dimethylformamide (6 mL). The mixture was degassed by gently bubbling argon through the solution for 30 minutes at room temperature. The mixture was then heated at 80 C. under argon until the reaction was complete (4 hours). The required product, 1-methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonyl-piperazine, and the bi-aryl product, 4-(4-methylpiperazin-1-ylsulfonyl)phenyl-phenylsulfonyl-4-methylpiperazine, were obtained in a ratio of 1:2 as indicated by LC/MS analysis.

Reference： [1]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 1373

31
[ 914610-39-2 ]
1-(2-((1H-indol-5-yl)oxy)ethyl)-6-bromo-4,4-dimethyl-1,2,3,4-tetrahydroquinoline [ No CAS ]
1-(2-((1H-indol-5-yl)oxy)ethyl)-4,4-dimethyl-6-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-1,2,3,4-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In water; N,N-dimethyl-formamide at 90℃; for 1.5h; Inert atmosphere;

Reference： [1]Juen, Ludovic; Brachet-Botineau, Marie; Parmenon, Cécile; Bourgeais, Jérôme; Hérault, Olivier; Gouilleux, Fabrice; Viaud-Massuard, Marie-Claude; Prié, Gildas [Journal of Medicinal Chemistry, 2017, vol. 60, # 14, p. 6119 - 6136]

32
[ 914610-39-2 ]
[ 75090-52-7 ]
4-chloro-7-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)quinoline [ No CAS ]