837-12-7|1-((4-Bromophenyl)sulfonyl)-4-methylpiperazine| Ambeed

Structure of 837-12-7

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Quality Control of [ 837-12-7 ] Purity: 98% SDS Specification

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Product Details of [ 837-12-7 ]

CAS No. :	837-12-7
Formula :	C₁₁H₁₅BrN₂O₂S
M.W :	319.22
SMILES Code :	CN1CCN(S(=O)(C2=CC=C(Br)C=C2)=O)CC1
MDL No. :	MFCD00595522
InChI Key :	CBNDEXDYZUNXBF-UHFFFAOYSA-N
Pubchem ID :	710729

Safety of [ 837-12-7 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Application In Synthesis of [ 837-12-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 837-12-7 ]

[ 837-12-7 ] Synthesis Path-Downstream 1~41

2
[ 867333-35-5 ]
[ 837-12-7 ]
[7-(2,6-dimethyl-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-amine [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5546 - 5550.

3
[ 837-12-7 ]
[ 486422-11-1 ]

Yield	Reaction Conditions	Operation in experiment
61%		4-(4-Methylpiperazin-l-ylsulfonyl)phenylboronic acidA solution of the starting bromide (1.00 g, 3.13 mmol) in dry tetrahydrofuran (10 mL) was cooled to -78C, followed by the dropwise addition of nBuLi (1.6 M in hexane , 9.78 mL, 15.66 mmol), whilst maintaining the temperature below -78C. The resulting reaction mixture was allowed to stir at -78C for 1 h. Triisopropyl borate (3.60 mL, 15.66 mmol) was added dropwise at -78C and stirred further for 45 min at -78C. The reaction mixture was allowed to warm to room temperature and stirred for an additional 12 h. A solution of NaOH (0.19 g, 4.70 mmol) in water (10 mL) was added and the reaction was then stirred for a further 12 h, at which time tetrahydrofuran was removed under reduced pressure. The pH was adjusted to 1 1 with HCl solution (1M) and the resulting solution extracted with ethyl acetate (3 x 5 mL) to recover the starting material. Then the pH was adjusted to 7 with HCl solution (1M) and the product extracted with ethyl acetate (3 x 5 mL), dried (MgS04) and concentrated under reduced pressure to give a colourless solid which was used without further purification (0.54 g, 61%); 1H NMR (400 MHz, DMSO-d6): δ 8.36 (bs, 2H), 8.02 (d, 2H, J = 8.0Hz), 7.69 (d, 2H, J = 8.0Hz), 2.94 (bs, 4H), 2.57 (bs, 4H) and 2.24 (s, 3H); 13C NMR (400 MHz, DMSO-d6): δ 136.0, 134.9, 134.7, 126.3, 53.1, 45.2 and 44.7. LC-MS APCI: Calculated for C11H17BN2O4S, 284; Observed m/z 284 [M]+.
58%		Triisopropyl borate (0.64 ML, 2.8 mmol) was added to a solution of 1- [ (4- bromophenyl) sulfonyl] -4-methylpiperazine (0.602 g, 1.9 mmol; described: in Keasling, H. H. et el. J. Med. Chez. 1965, 8, 548-550) in anhydrous tetrahydrofuran (7 mL) at-78 C under a nitrogen atmosphere followed by dropwise addition of n-butyllithium (1.4 mL, 2.2 mmol). The resulting mixture was stirred at-78 C for 2 h and at room temperature for another 16 h. Water (2.0 mL) was added and the mixture stirred for 30 min and evaporated to dryness. The residue was pre-adsorbed onto silica and purified by column chromatography using methylene chloride/methanol, (9: 1 to 1: 9), as the eluent. The product was re-crystallized from water to give 311 mg (58% yield) of the title compound as white crystals: mp 215-218 C ; 1H NMR (DMSO-d6,400 MHz) 8 10.89 (br s, 1 H), 8.47 (BR S, 2 H), 8.05 (d, J = 8 HZ, 2 H), 7.73 (d, J = 8 HZ, 2 IT), 3.77 (m, 2 H), 3.40 (m, 2 H), 3.13 (m, 2 H), 2.71 (s, 3 H), 2.65 (m, 2 H); 13C NMR (DMSO-d6,100 MHz) 8 133. 7, 133.3, 124.7, 49.8, 41.6, 41.4 ; MS (TSP) m/z 285 (M++1).
58%	With n-butyllithium; Triisopropyl borate; In tetrahydrofuran; at -78 - 20℃; for 18h;	Triisopropyl borate (0.64 ML, 2.8 mmol) was added to a solution of 1- [ (4- bromophenyl) sulfonyl] -4-methylpiperazine (0.602 g, 1.9 mmol; described: in Keasling, H. H. et el. J. Med. Chem. 1965, 8, 548-550) in anhydrous tetrahydrofuran (7 mL) at-78 C under a nitrogen atmosphere followed by dropwise addition of n-butyllithium (1.4 mL, 2.2 mmol). The resulting mixture was stirred at-78 C for 2 h and at room temperature for another 16 h. Water (2.0 mL) was added and the mixture stirred for 30 min and evaporated to dryness. The residue was pre-adsorbed onto silica and purified by column chromatography on silica using methylene CHLORIDE/METHANOL, (9: 1 to 1: 9), as the eluent. The product was re-crystallized from water to give 311 mg (58% yield) of the title compound as white crystals: mp 215-218 C ; 1H NMR (DMSO-d6,400 MHz) 8 8.47 (br s, 2 H), 8.05 (d, J = 8 Hz, 2 H), 7.73 (d, J = 8 HZ, 2 H), 3.77 (m, 2 H), 3.40 (m, 2 H), 3.13 (m, 2 H), 2.71 (s, 3 H), 2.65 (m, 2 H) ; 13C NMR (DMSO-d6,100 MHz) 8 133.7, 133.3, 124.7, 49.8, 41.6, 41.4 ; MS (TSP) M/Z 285 (M++1).

References: [1]Patent: WO2011/86531,2011,A2 .Location in patent: Page/Page column 58-59.
[2]Patent: WO2004/55006,2004,A1 .Location in patent: Page 29.
[3]Patent: WO2004/55009,2004,A1 .Location in patent: Page 33-34.
[4]Journal of Medicinal Chemistry,2012,vol. 55,p. 9107 - 9119,13.

4
[ 712268-41-2 ]
[ 837-12-7 ]
[ 712268-49-0 ]

Yield	Reaction Conditions	Operation in experiment
53%	With potassium tert-butylate;1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; at 95℃; for 16h;	To a mixture of (N-phenyl-4,4'-bipyridine-2, 2'-diamine (27 mg, 0.10 mmol), tris (dibenzylideneacetone) dipalladium (0) (9.2 mg, 0.01 mmol), 1. 1'- bis (diphenylphosphino) ferrocene (11 mg, 0.02 mmol) and sodium tert-butoxide (14.4 mg, 0.15 mmol) in 2 ml dry dioxane under nitrogen was added 1- [ (4-BROMOPHENYL) sulfonyl] -4- methylpiperazine (32 mg, 0.10 mmol). The mixure was stirred under argon for 16 h at 95 C, filtered, evaporated under reduced pressure, and chromatographed on C8-silica (Waters XTerra MS C8, 19X300MM, 7um) using an automated preparative HPLC system (Gilson autopreparative HPLC, diode array detection) with a gradient of 20%-60% acetonitrile in 0.1 M aqueous ammonium acetate for 13 minutes at 20ML/MIN. Appropriate fractions were combined and concentrated to dryness to yield 26.6 mg (53 %) of the title compound. The material was dissolved in methanol and 1M hydrochloric acid (0.5 mL) was added. The solution was evaporated to dryness, dissolved in water and freeze DRIED. 1H NMR (DA0) 8 7.86-6. 80 (15H), 3.65 (d, J = 12.0 Hz, 2H), 3.38 (d, 2H), 3.02 (m, 2H), 2.69 (s, 3H), 2.59 (m, 2H). HPLC-MS (Waters Exterra C8-column, 8.6 min gradient of 0-100% methanol containing 0. 1 % trifluoroacetic acid. UV-diode array detector, CLND and MSD-ESI detection) shows a single compound with m/z 501 (M+1). C27H28N602S, MW=500.6.

References: [1]Patent: WO2004/52880,2004,A1 .Location in patent: Page 40.

5
[ 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.

References: [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.

6
[ 109-01-3 ]
[ 98-58-8 ]
[ 837-12-7 ]

Yield	Reaction Conditions	Operation in experiment
89%	In tetrahydrofuran; at 20℃; for 4h;	l-(4-Bromophenylsulfonyl)-4-methylpiperazine1-methylpiperazine ( 1 1 .76 g, 1 17.4 1 mmol) was added to a solution of 4-[(4- bromobenzene)]sulfonylchloride (3.00 g, 11.74 mmol) in tetrahydrofuran (20 mL). The resulting reaction mixture was stirred at room temperature for 4 h. The solvent was removed and the residue was dissolved in dichloromethane (40 mL). The solution was washed with saturated aqueous sodium hydrogen carbonate (3 x 10 mL), saturated aqueous sodium chloride (2 x 10 mL), dried (MgS04) and concentrated under reduced pressure to give a colourless solid. The remaining residue was subjected to column chromatography on silica gel using dichloromethane/methanol in a 9.0: 1.0 v/v ratio as eluent (3.34 g, 89 %); 1H NMR (300 MHz, CDC13): δ 7.67-7.57 (m, 4H), 3.02 (t, 4H, J = 4.8Hz), 2.45 (t, 4H, J = 5.1Hz) and 2.24 (s, 3H); 13C NMR (300 MHz, CDC13): δ 134.7, 132.4, 129.4, 128.0, 54.1, 46.0 and 45.8. LC-MS APCI: Calculated for CnHi5BrN202S, 318; Observed m/z 318 [M]+.
84%	In dichloromethane; for 12h;	Synthesis of l-(4-bromo-benzenesulfonyl)-4~methyl-piperazine (R34) R33 (800 mg, 3.1 mmol) is dissolved in DCM, N-methyl-piperazine (313 mg, 3.1 mmol) is added and stirred for 12 h. After addition of 2 mL IN HCl under stirring the phases are separated. The organic phase is dried over MgS04 and after filtration evaporated in vacuo. Yield: 84 % m/z 319 (M+H)+.
84%	In dichloromethane; for 12h;	Synthesis of 1-(4-bromo-benzenesulfonyl)-4-methyl-piperazine (R11) [0290] DCM, N-methyl-piperazine (313 mg, 3.1 mmol) is added and stirred for 12 h. After addition of 2 mL 1N HCl under stirring the phases are separated. The organic phase is dried over MgSO4 and after filtration evaporated in vacuo. Yield: 84% m/z 319 (M+H)+

84%	In dichloromethane; for 12h;	R10 (800 mg, 3.1 mmol) is dissolved in DCM, N-methyl-piperazine (313 mg, 3.1 mmol) is added and stirred for 12 h. After addition of 2 mL IN HC1 under stirring the phases are separated. The organic phase is dried over MgS04 and after filtratrion evaporated in vacuo. Yield:84 % m/z 319 (M+H)+.
84%	In dichloromethane; for 12h;	R33 (800 mg, 3.1 mmol) is dissolved in DCM, N-methylpiperazine (313 mg, 3.1 mmol) is added and stirred for 12 h. After addition of 2 mL 1N HCl under stirring the phases are separated. The organic phase is dried over MgSO4 and after filtration evaporated in vacuo. Yield: 84% m/z 319 (M+H)+.
71%	With pyridine; In dichloromethane; at 20℃; for 16h;	4-Bromobenzene-l-sulfonyl chloride (2.56 g, 10 mmol) in anhydrous CH2Cl2 (10 mL) was added to a mixture of 1-methylpiperazine (2.0 g, 20 mmol), pyridine (2.37 g, 30 mmol) and anhydrous CH2Cl2 (10 mL) at 0C. The mixture was stirred at room temperature for 16 h, concentrated, recrystallised, and dried over P2O5 to yield the sub-title compound (2.27 g, 71%).
	With 4-methyl-morpholine; In dichloromethane; at 0 - 20℃;	N-methylmorpholine (60 g, 65 mL, 0.6 mol) is dissolved in DCM (100 ml_), to which 1- methylpiperazine (30.5 g, 0.3 mol) is added. The reaction is cooled to O0C, after which a solution of 4-bromo-benzenesulfonyl chloride (75.8 g, 0.296 mol) in DCM (100 mL) is added dropwise. The reaction is allowed to warm to RT overnight. The reaction mixture is then concentrated and water (1 L) is added. The solids that are formed are filtered and the filtrate is extracted with EtOAc (500 mL). The organic layer is washed with saturated brine, dried over MgSO4, filtered and concentrated to afford 1-(4-bromo-benzenesulfonyl)-4-methyl- piperazine as a pale yellow solid: LC/MS 321.0 (M+1); 1H NMR (400 MHz, CDCI3) ? 2.3 (s, 3 H) 2.5 (m, 4 H) 3.0 (m, 4 H) 7.6 (dt, J=8.8, 2.0 Hz, 2 H) 7.7 (dt, J=8.8, 2.1 Hz, 2 H).
	With triethylamine; In dichloromethane; at 20℃; for 5h;	A1. 1-(4-Bromo-benzenesulfonyl)-4-methyl-piperazine; 1.54 g of 4-Bromo-benzenesulphonyl chloride are dissolved in 35 ml of dichloromethane under an atmosphere of dry nitrogen. Subsequently, 691 mg of N-methyl-piperazine and 1.67 ml of triethylamine are added dropwise. The reaction mixture is stirred for 5 h at room temperature. The solution is diluted with 75 ml of water and extracted twice with each 75 ml of dichloromethane. The organic layer is dried using Na2SO4, filtered with suction and concentrated in vacuo to obtain 1.83 mg of the title compound EPO <DP n="29"/>as a colorless solid. M.p. 154-1550C. ESI-MS: 319.1/321.1 (MH+). TLC: Rf = 0.33 (dichloromethane/ methanol 20:1 parts per volume).
	With sodium hydrogencarbonate; In dichloromethane;	Step a: 1-(4-Bromophenylsulfonyl)-4-methylpiperazine A solution of 4-bromobenzene-1-sulfonyl chloride (256 mg, 1.00 mmol) in 1 mL of dichloromethane was slowly added to a vial (40 mL) containing 5 mL of a saturated aqueous solution of sodium bicarbonate, dichloromethane (5 mL) and 1-methylpiperazine (100 mg, 1.00 mmol). The reaction was stirred at room temperature overnight. The phases were separated and the organic layer was dried over magnesium sulfate. Evaporation of the solvent under reduced pressure provided the required product, which was used in the next step without further purification. ESI-MS m/z calc. 318.0, found 318.9 (M+1)+. Retention time of 1.30 minutes. 1H NMR (300 MHz, CDCl3) δ 7.65 (d, J=8.7 Hz, 2H), 7.58 (d, J=8.7 Hz, 2H), 3.03 (t, J=4.2 Hz, 4H), 2.48 (t, J=4.2 Hz, 4H), 2.26 (s, 3H).
	With sodium hydrogencarbonate; In dichloromethane; water; at 20℃;	A solution of 4-bromobenzene-1-sulfonyl chloride (256 mg, 1.00 mmol) in 1 mL of dichloromethane was slowly added to a vial (40 mL) containing 5 mL of a saturated aqueous solution of sodium bicarbonate, dichloromethane (5 mL) and 1-methylpiperazine (100 mg, 1.00 mmol). The reaction was stirred at room temperature overnight. The phases were separated and the organic layer was dried over magnesium sulfate. Evaporation of the solvent under reduced pressure provided the required product, which was used in the next step without further purification. ESI-MS m/z calc. 318.0. found 318.9 (M+1)+. Retention time of 1.30 minutes. 1H NMR (300 MHz, CDCl3) δ 7.65 (d, J=8.7 Hz, 2H), 7.58 (d, J=8.7 Hz, 2H), 3.03 (t, J=4.2 Hz, 4H), 2.48 (t, J=4.2 Hz, 4H), 2.26 (s, 3H).

References: [1]Journal of Heterocyclic Chemistry,2019,vol. 56,p. 1260 - 1274.
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 5522 - 5537.
[3]Patent: WO2011/86531,2011,A2 .Location in patent: Page/Page column 57-58.
[4]Patent: WO2014/140075,2014,A1 .Location in patent: Page/Page column 205-206.
[5]Patent: US2014/275114,2014,A1 .Location in patent: Paragraph 0290.
[6]Patent: WO2014/140078,2014,A1 .Location in patent: Page/Page column 67.
[7]Patent: US2014/275025,2014,A1 .Location in patent: Paragraph 0523; 0524.
[8]Journal of Medicinal Chemistry,2022,vol. 65,p. 1265 - 1282.
[9]Patent: WO2005/123673,2005,A1 .Location in patent: Page/Page column 60.
[10]Patent: WO2007/41365,2007,A2 .Location in patent: Page/Page column 39.
[11]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 6575 - 6577.
[12]Patent: WO2007/39581,2007,A1 .Location in patent: Page/Page column 27-28.
[13]Patent: US2011/98311,2011,A1 .
[14]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 1372.

7
[ 867330-72-1 ]
[ 837-12-7 ]
[7-(2-chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With potassium tert-butylate;palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; for 18h;Heating / reflux;	7-(2-chloro-5-methoxy-phenyl)-5-methyl-benzo[1,2,4]triazin-3-ylamine (1.0 equiv., 0.75 mmol), <strong>[837-12-7]1-(4-bromo-benzenesulfonyl)-4-methyl-piperazine</strong> (1.5 equiv., 1.125 mmol), Xantphos (0.1 equiv., 0.074 mmol), palladium acetate (0.05 equiv., 0.0375 mmol), and potassium-tert-butoxide (2.0 equiv, 1.5 mmol) were dissolved in 20 mL of dioxane and bubbled with argon. The reaction was stirred in an oil bath at 100 C. for 18 h under an argon blanket. The reaction was cooled to room temperature and filtered to remove inorganics, concentrated under reduced pressure, then brought up in EtOAc and extracted using saturated NaHCO3 and brine. The organics were dried over Na2SO4 and concentrated under reduced pressure then precipitated using EtOAc/Hexanes (1:5 v/v) to afford brown solid (182.3 mg, 45% yield). MS (ES+): m/z=540 LC retention time: 2.67 min.

References: [1]Patent: US2005/245524,2005,A1 .Location in patent: Page/Page column 43.

8
[ 3073-77-6 ]
[ 837-12-7 ]
[ 910903-94-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium tert-butylate;palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; for 18h;	Example 16. f4-(4-MethvI-piperazine-l-suIfonvI)-phenvIl-(5-nitro-pyrimidin-2-yl)- amine (11); [0146] 5-Nitro-pyrimidin-2-ylamine (1.78 mmol, 1.0 equiv), l-(4-bromo- benzenesulfonyl)-4-methyl-piperazine (2.68 mmol, 1.5 equiv), Pd(OAc)2 (0.089mmol, 0.05eq), Xantphos (0.178 mmol, 0.1 equiv) and potassium-t-butoxide (3.56 mmol, 2.0 equiv) were suspended in 15 mL of dioxane and refluxed at 100C under an argon atmosphere for 18 h. The mixture was allowed to cool to room temperature, filtered and washed with DCM. The filtrate was concentrated under reduced pressure and a silica plug was run to purify material (5% MeOH/DCM) to afford the title compound as a pale yellow solid (758 mg, 95%). MS (ES+): m/z = 379 (M+H)+. LC retention time: 1.76 min.

References: [1]Patent: WO2006/101977,2006,A2 .Location in patent: Page/Page column 44-45.

9
[ 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).

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

10
[ 933784-97-5 ]
[ 837-12-7 ]
5-fluoro-N-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-4-[2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl]pyrimidin-2-amine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
11%		General Method DDl (1.0 equiv.), D2 (0.85-1.24 equiv.) and sodium tert-butoxide (1.34-1.46 equiv.) were mixed in 1,4-dioxane and the mixture was flushed with argon for 5-10 minutes before Pd(OAc)2 (0.04-0.082 equiv.) and Pd(^-Bu3P)2 (0.044-0.06 equiv.) were added. The mixture was flushed with argon then heated in a sealed tube at +110-+ 120 C until the reaction was complete (as monitored by TLC or LC-MS). If the reaction was not complete after 24 h more Pd(OAc)2, Pd(t-Bu3P)2 and sodium tert-butoxide were added. The solvent was removed in vacuo and the residue was partitioned between CH2Cl2 and water. After extraction the organic layer was dried (Na2SO4), filtered and evaporated. The crude of the free base was purified using preparative HPLC. MeCN was evaporated in vacuo and the aqueous phase was extracted with CH2Cl2. The organic phase was washed with water at pH 9 (diluted NaHCO3 solution), dried (Na2SO4), filtered and evaporated. The residue was dissolved in CH2Cl2 and the HCl-adduct of the product was precipitated from the solution by addition of 0.1M HCl in ether (1-5 equiv. HCl). The solvent was evaporated and the residue was dissolved in water and freeze dried.Example 7(f) 5-Fluoro-N-{4-[(4-methylpiperazin-l-yl)sulfonyl]phenyl}-4-[2-methyl-l- (tetrahydro-2H-pyran-4-yl)-lH-imidazol-5-yl]pyrimidin-2-amine hydrochlorideThe title compound was prepared in accordance with the general method D, with the exception that the base of the product was purified by flash chromatography(CHCl3/Me0H/NH3 aq. 200:10:1) before purification by preparative HPLC. Using 5- fluoro-4-[2-methyl-l-(tetrahydro-2H-pyran-4-yl)-lH'-imidazol-5-yl]pyrimidm-2 -amine (0.075 g, 0.27 mmol, obtained from Example 7(e)), l-(4-bromo-benzenesulfonyl)-4- methylpiperazine (described in WO 2003004472) (0.108 g, 0.338 mmol), sodium tert- butoxide (0.036 g, 0.38 mmol), Pd(OAc)2 (0.012 g, 0.054 mmol) and Pd(^-Bu3P)2 (0.14 g, 0.027 mmol), the title compound (0.018 g, 11%) was obtained as a yellow solid. 1H NMR (DMSO-rf* 300 MHz) δ 10.64 (br s, 1 H), 10.43 (s, 1 H), 8.90 (s, 1 H), 8.07 (s, 1 H), 7.96 (d, J= 8.4 Hz, 2 H), 7.70 (d, J= 8.4 Hz, 2 H), 5.03-4.93 (m, 1 H), 3.90-3.70 (m, 4 H), 3.36-3.15 (m, 4 H), 2.81 (s, 3 H), 2.74 (s, 3 H), 2.25-2.15 (m, 2 H), 2.00-1.92 (m, 2 H); MS (ESI) m/z 516 (M+l).

References: [1]Patent: WO2007/40440,2007,A1 .Location in patent: Page/Page column 62; 50.

11
[ 1160918-11-5 ]
[ 837-12-7 ]
C₂₈H₂₈N₆O₂S [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 6575 - 6577.

12
[ 1160918-76-2 ]
[ 837-12-7 ]
C₂₉H₃₀N₆O₂S [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 6575 - 6577.

13
[ 837-12-7 ]
(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 ]

References: [1]Patent: WO2012/130299,2012,A1 .

14
[ 5419-55-6 ]
[ 837-12-7 ]
C₁₇H₂₉BN₂O₄S [ No CAS ]