[ CAS No. 703-12-8 ] {[proInfo.proName]}

Name: 703-12-8|4-Bromo-N-methylbenzenesulfonamide|98%
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SKU: A446319
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Quality Control of [ 703-12-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 703-12-8 ]

SDS Specification

Alternatived Products of [ 703-12-8 ]

Product Details of [ 703-12-8 ]

CAS No. :	703-12-8	MDL No. :	MFCD00993162
Formula :	C₇H₈BrNO₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZAHMEHGOFNLRQN-UHFFFAOYSA-N
M.W :	250.11	Pubchem ID :	101215
Synonyms :

Calculated chemistry of [ 703-12-8 ] Expand+

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	50.04
TPSA :	54.55 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.86 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.65
Log Po/w (XLOGP3) :	1.36
Log Po/w (WLOGP) :	2.44
Log Po/w (MLOGP) :	1.4
Log Po/w (SILICOS-IT) :	1.03
Consensus Log Po/w :	1.57

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.49
Solubility :	0.818 mg/ml ; 0.00327 mol/l
Class :	Soluble
Log S (Ali) :	-2.11
Solubility :	1.95 mg/ml ; 0.0078 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.62
Solubility :	0.0601 mg/ml ; 0.00024 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.05

Safety of [ 703-12-8 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P264-P270-P301+P312-P330	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 703-12-8 ]

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

Upstream synthesis route of [ 703-12-8 ]
Downstream synthetic route of [ 703-12-8 ]

[ 703-12-8 ] Synthesis Path-Upstream 1~8

1
[ 593-51-1 ]
[ 98-58-8 ]
[ 703-12-8 ]

Yield	Reaction Conditions	Operation in experiment
89.74%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16 h;	To a stirred solution of Methyl amine hydrochloride salt (0.13 g, 1.97 mmol) in DCM, DIPEA (0.52 mL, 2.95 mmol) and 4-bromobenzene-1-sulfonyl chloride (0.25 g, 0.98 mmol) were added and reaction allowed to stir at RT for 16 h. Progress of reaction was monitored by TLC. On completion, reaction mixture was quenched with water and extracted with DCM. The organic layer was dried on sodium sulfate and concentrated under reduced pressure to 1-bromo-4-(methylaminosulfonyl)benzene(0.220 g, 89.74percent) as yellow semisolid. (0432) MS: 248.0 [M⁻−1].
0.8 g	With triethylamine In dichloromethane at 20℃; for 2 h; Inert atmosphere	In a 100-mL round-bottomed flask, 4-bromobenzenesulfonyl chloride (1 g, 4 mmol, Sigma-Aldrich, India) was dissolved in DCM (10 mL) at rt under nitrogen atmosphere. Triethylamine (1.7 mL, 7.8 mmol, SD Fine-Chem, India) and methylamine hydrochloride (350 mg, 5.46 mmol, Sigma-Aldrich, India) were added sequentially to the above solution at rt under nitrogen atmosphere. The reaction mixture was stirred at rt under nitrogen atmosphere for 2 h. The reaction mixture was diluted with ice-cold water (10 mL) and DCM (20 mL). The organic layer was separated, washed with water and brine, dried over anhydrous Na₂S0₄ and filtered. The filtrate was concentrated under reduced pressure to give 4- bromo-N-methylbenzenesulfonamide (0.8 g) as a white solid.

Reference： [1] Patent: US2017/291910, 2017, A1, . Location in patent: Paragraph 0430-0432
[2] Journal of the American Chemical Society, 1923, vol. 45, p. 2697
[3] Patent: WO2014/35872, 2014, A1, . Location in patent: Page/Page column 136-137

2
[ 74-89-5 ]
[ 98-58-8 ]
[ 703-12-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	at 20℃; for 0.0833333 h;	Example 13: 5-(4-[(Methylamino)sulfonyliphenyl)-2-(2-phenylethyl) pentanoic acida) Synthesis of 4-Bromo-λ/-methylbenzenesulfonamide. MeNH₂ (7.5 ml, 8 M solution in EtOH, 60 mmol) was added to a solution of 4- bromobenzenesulfonyl chloride (5.0 g, 19.568 mmol) in THF (120 ml). The reaction mixture was stirred at room temperature for 5 min, poured into NH₄CI (saturated aqueous solution, 300 ml) and extracted with EtOAc (500 ml). The <n="32"/>organic layer was dried over Na₂SO₄ (anhydrous), filtered and concentrated, to furnish 4-bromo-W-methylbenzenesulfonamide, which was submitted to next step without further purification (4.60 g, white solid, yield: 94percent). 1H NMR (CDCI₃, 250 MHz) δ ppm: 7.70 (m, 4H), 4.49 (bs, 1 H), 2.67 (d, J = 5.2 Hz, 3H).
94%	at 0 - 20℃; for 2 h; Inert atmosphere	To a stirred solution of 4-bromobenzene-l-sulfony chloride (BY; 2.5 g, 9.78 mmol) in CH₂CI₂ (20 mL) under inert atmosphere was added 2M methylamine in THF (10 mL, 19.56 mmol) at 0 °C. The reaction was then warmed to RT and stirred for 2 h. After complete consumption of the starting material, the volatiles were evaporated under reduced pressure. The residue was neutralized with saturated sodium bicarbonate solution (30 mL) and the compound was extracted with CH₂CI₂ (3x25 mL). The combined organic extracts were washed with water (30 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude. The crude was triturated with diethyl ether/pentane (3x15 mL) to afford BZ (2 g, 94percent) as a white solid. *H NMR (500 MHz, DMSO-i: δ 7.83 (d, J = 8.5 Hz, 2H), 7.70 (d, J = 8.5 Hz, 2H), 7.54 (s, 1H), 2.41 (d, / = 13.5 Hz, 3H). MS (ESI): m/z 250 [M+l]⁺
92%	at 0 - 20℃; for 18 h;	To a solution of 4-bromobenzene-1-sulfonyl chloride (3 g, 11.74 mmol) in DCM (20 mL) at 0°C was added methylamine (29 mL of a 2M solution in THF, 58.7 mmol) and the reaction mixture and stirred at room temperature for 18 hours. The reaction mixture was diluted with DCM (100 mL) and washed with ammonium chloride solution (20 mL). The organic layer was collected and dried overmagnesium sulfate, filtered and concentrated in vacuo. The resulting emulsion was purified by silica gel chromatography eluting with 0-40percent Heptane: ethyl acetate to yield the desired compound as a white solid (2.7 g, 92percent yield). ‘H NMR (250 MHz, DMSO-d6) 7.91 — 7.79 (m, 2H), 7.79 — 7.65 (m, 2H), 7.56 (s, 1H), 2.43 (s, 3H).

82%	at 20℃; for 1 h;	To synthesize compound 67, to a solution of 4-bromosulfonyl chloride (5.0 g, 20 mmol) in DCM (30 mL) was added methyl amine (2 M in THF, 20 mL, 40 mmol). The mixture was stirred at room temperature for 1 h and then the solvent was removed. A saturated NaHCO₃solution was added to the residue and then extracted with EtOAc. The combined organic layers were washed with water, brine, dried over anhydrous Na₂SO₄and filtered. The filtrate was concentrated and the residue triturated in hexane. Compound 67 was obtained as a white solid after filtration (4.0 g, 82percent). ¹H NMR (DMSO-d₆): δ 2.41 (d, J=5.0 Hz, 3H), 7.56 (q, J=4.9 Hz, 1H), 7.70 (d, J=8.7 Hz, 2H), 7.83 (d, J=8.7 Hz, 2H).
28%	for 16 h; Sealed tube	4-Bromobenzene sulfonyl chloride (0.40 g, 1.56 mmol) and methylamine (10 mL, 33percent in ethanol) were stirred in a sealed tube for 16 hours. The reaction mixture was concentrated in vacuo onto the Celite.(R). reagent. The crude product was purified via Isco chromatography (the Redisep.(TM). column, silica, gradient 0-3percent ethyl acetate-dichloromethane) to provide 4-bromo-N-methylbenzenesulfonamide (0.11 g, 28percent). MS (ESI) m/z 250. High performance liquid chromatography (HPLC) purity 100.0percent at 210-370 nm, 7.4 min.; the Xterra.(R). RP18 column, 3.5μ, 150*4.6 mm column, 1.2 mL/min., 85/15-5/95 (ammonium formate buffer pH=3.5/Acetonitrile (ACN)+MeOH) for 10 min., hold 4 min.
1.80 g	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran; dichloromethane at 0℃; for 0.166667 h;	To a stirring solution of 4-bromobenzenesulfonyl chloride (2.0 g, 7.8 mmol, Sigma-Aldrich, St. Louis, MO) and DIEA (1.50 mL, 8.61 mmol) in CH₂C1₂ (25 mL) at 0 °C, was added methanamine (2 M in THF, 7.83 mL, 15.7 mmol, Sigma-Aldrich, St. Louis, MO). After 10 min, the reaction mixture was treated with 1 M KH₂P0₄ (50 mL). The organic was concentrated under reduced pressure and then purified by silica gel chromatography (0 to 4percent of MeOH/CH₂Cl₂) to afford 4-bromo-N-methylbenzenesulfonamide (1.80 g) as a white solid.

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 14, p. 3880 - 3885
[2] Patent: WO2009/80722, 2009, A2, . Location in patent: Page/Page column 30-31
[3] Patent: WO2014/117090, 2014, A1, . Location in patent: Page/Page column 130
[4] Patent: WO2017/70081, 2017, A1, . Location in patent: Page/Page column 190
[5] Chemistry - A European Journal, 2017, vol. 23, # 57, p. 14345 - 14357
[6] Patent: US2005/245524, 2005, A1, . Location in patent: Page/Page column 80
[7] Patent: US2008/221201, 2008, A1, . Location in patent: Page/Page column 8
[8] Patent: WO2004/63179, 2004, A1, . Location in patent: Page 93
[9] Patent: WO2007/56341, 2007, A1, . Location in patent: Page/Page column 158
[10] Patent: US2008/9524, 2008, A1, . Location in patent: Page/Page column 390
[11] Journal of Organic Chemistry, 2008, vol. 73, # 6, p. 2428 - 2431
[12] Patent: WO2008/82487, 2008, A2, . Location in patent: Page/Page column 115
[13] Organic Letters, 2011, vol. 13, # 6, p. 1556 - 1559
[14] Patent: WO2011/48082, 2011, A1, . Location in patent: Page/Page column 85
[15] Patent: WO2014/35872, 2014, A1, . Location in patent: Page/Page column 134
[16] Journal of Medicinal Chemistry, 2014, vol. 57, # 7, p. 3094 - 3116
[17] Patent: US2015/231142, 2015, A1, . Location in patent: Paragraph 1160
[18] Organic Letters, 2016, vol. 18, # 9, p. 2280 - 2283
[19] Patent: EP1798229, 2007, A1, . Location in patent: Page/Page column 108
[20] Organic Letters, 2017, vol. 19, # 21, p. 5844 - 5847
[21] Chemical Communications, 2018, vol. 54, # 60, p. 8403 - 8406

3
[ 98-58-8 ]
[ 703-12-8 ]

Reference： [1] Patent: US5380721, 1995, A,
[2] Patent: US2011/98311, 2011, A1,
[3] Journal of Fluorine Chemistry, 2016, vol. 188, p. 65 - 75
[4] Journal of Fluorine Chemistry, 2016, vol. 188, p. 65 - 75

4
[ 67-56-1 ]
[ 701-34-8 ]
[ 703-12-8 ]

Reference： [1] Organic Letters, 2017, vol. 19, # 21, p. 5790 - 5793
[2] RSC Advances, 2012, vol. 2, # 23, p. 8645 - 8652

5
[ 1158827-44-1 ]
[ 703-12-8 ]

Reference： [1] Journal of Fluorine Chemistry, 2016, vol. 188, p. 65 - 75
[2] Journal of Fluorine Chemistry, 2016, vol. 188, p. 65 - 75

6
[ 106-53-6 ]
[ 703-12-8 ]

Reference： [1] Patent: US2017/291910, 2017, A1,

7
[ 42111-84-2 ]
[ 74-88-4 ]
[ 703-12-8 ]

Reference： [1] Synthetic Communications, 1989, vol. 19, # 9-10, p. 1499 - 1504

8
[ 86674-11-5 ]
[ 67-56-1 ]
[ 138-36-3 ]
[ 703-12-8 ]

Reference： [1] Journal of Organic Chemistry USSR (English Translation), 1983, vol. 19, # 4, p. 671 - 675[2] Zhurnal Organicheskoi Khimii, 1983, vol. 19, # 4, p. 761 - 766

[ 703-12-8 ] Synthesis Path-Downstream 1~90

1
[ 593-51-1 ]
[ 98-58-8 ]
[ 703-12-8 ]

Yield	Reaction Conditions	Operation in experiment
89.74%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 16h;	To a stirred solution of Methyl amine hydrochloride salt (0.13 g, 1.97 mmol) in DCM, DIPEA (0.52 mL, 2.95 mmol) and 4-bromobenzene-1-sulfonyl chloride (0.25 g, 0.98 mmol) were added and reaction allowed to stir at RT for 16 h. Progress of reaction was monitored by TLC. On completion, reaction mixture was quenched with water and extracted with DCM. The organic layer was dried on sodium sulfate and concentrated under reduced pressure to 1-bromo-4-(methylaminosulfonyl)benzene(0.220 g, 89.74%) as yellow semisolid. (0432) MS: 248.0 [M--1].
0.8 g	With triethylamine; In dichloromethane; at 20℃; for 2h;Inert atmosphere;	In a 100-mL round-bottomed flask, 4-bromobenzenesulfonyl chloride (1 g, 4 mmol, Sigma-Aldrich, India) was dissolved in DCM (10 mL) at rt under nitrogen atmosphere. Triethylamine (1.7 mL, 7.8 mmol, SD Fine-Chem, India) and methylamine hydrochloride (350 mg, 5.46 mmol, Sigma-Aldrich, India) were added sequentially to the above solution at rt under nitrogen atmosphere. The reaction mixture was stirred at rt under nitrogen atmosphere for 2 h. The reaction mixture was diluted with ice-cold water (10 mL) and DCM (20 mL). The organic layer was separated, washed with water and brine, dried over anhydrous Na2S04 and filtered. The filtrate was concentrated under reduced pressure to give 4- bromo-N-methylbenzenesulfonamide (0.8 g) as a white solid.

Reference： [1]Patent: US2017/291910,2017,A1 .Location in patent: Paragraph 0430-0432
[2]Journal of the American Chemical Society,1923,vol. 45,p. 2697
[3]Patent: WO2014/35872,2014,A1 .Location in patent: Page/Page column 136-137

2
[ 37167-62-7 ]
[ 703-12-8 ]
[ 52260-15-8 ]

Reference： [1]Journal of Organic Chemistry,1974,vol. 39,p. 3219 - 3223

3
[ 703-12-8 ]
[ 56059-54-2 ]

Reference： [1]Synthesis,1975,vol. No. 1,p. 39 - 40

4
[ 37167-62-7 ]
[ 703-12-8 ]
[ 98-59-9 ]
[ 53119-81-6 ]

Reference： [1]Journal of Organic Chemistry,1974,vol. 39,p. 3219 - 3223

5
[ 703-12-8 ]
[ 86674-11-5 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1983,vol. 19,p. 671 - 675
Zhurnal Organicheskoi Khimii,1983,vol. 19,p. 761 - 766
[2]Journal of Organic Chemistry,2008,vol. 73,p. 2428 - 2431

6
[ 86674-11-5 ]
[ 67-56-1 ]
[ 138-36-3 ]
[ 703-12-8 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1983,vol. 19,p. 671 - 675
Zhurnal Organicheskoi Khimii,1983,vol. 19,p. 761 - 766

7
[ 42111-84-2 ]
[ 74-88-4 ]
[ 703-12-8 ]

Reference： [1]Synthetic Communications,1989,vol. 19,p. 1499 - 1504

8
[ 50-00-0 ]
[ 703-12-8 ]
4-bromo-<i>N</i>-chloromethyl-<i>N</i>-methyl-benzenesulfonamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2000,vol. 8,p. 1629 - 1636

9
[ 108-30-5 ]
[ 701-34-8 ]
[ 74-88-4 ]
ArgoGel-Rink-NH-Fmoc resin [ No CAS ]
[ 703-12-8 ]

Reference： [1]Organic Letters,2001,vol. 3,p. 2977 - 2980

10
[ 30418-59-8 ]
[ 703-12-8 ]
[ 945244-16-6 ]

Yield	Reaction Conditions	Operation in experiment
50%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 20 - 80℃;	Step b: 3'-Amino-N-methylbiphenyl-4-sulfonamide (C-3) To a solution of 4-bromo-N-methyl-benzene sulfonamide (2.49 g, 10 mmol) in DMF (20 mL) was added 3-amino-phenyl boronic acid (1.51 g, 11 mmol), Pd(PPh3)4 (90 mg, 0.30 mmol), potassium carbonate (1.52 g, 11 mmol) and water (5 mL). The resulting mixture was degassed by gently bubbling argon through the solution for 5 minutes at 20 C. The reaction mixture was then heated at 80 C. overnight. The reaction was filtered through a pad of silica gel, which was washed with CH2Cl2 (50 mL*3). The combined organics were concentrated under reduced pressure to give crude product, which was washed with EtOAc to give pure 3'-amino-N-methylbiphenyl-4-sulfonamide (C-3) (1.3 g, 50%). 1H NMR (300 MHz, CDCl3) delta 7.85 (d, J=8.7 Hz, 2H), 7.75 (d, J=8.7 Hz, 2H), 7.19 (t, J=7.8 Hz, 1H), 6.95-7.01 (m, 2H), 6.73-6.77 (m, 1H), 2.54 (s, 3H). MS (ESI) m/e (M+H+) 263.0.
50%	With potassium carbonate;Pd(PPh3)4; In water; N,N-dimethyl-formamide;	Step b: 3'-Amino-N-methylbiphenyl-4-sulfonamide (C-3) To a solution of 4-bromo-N-methyl-benzene sulfonamide (2.49 g, 10 mmol) in DMF (20 mL) was added 3-amino-phenyl boronic acid (1.51 g, 11 mmol), Pd(PPh3)4 (90 mg, 0.30 mmol), potassium carbonate (1.52 g, 11 mmol) and water (5 mL). The resulting mixture was degassed by gently bubbling argon through the solution for 5 minutes at 20 C. The reaction mixture was then heated at 80 C. overnight. The reaction was filtered through a pad of silica gel, which was washed with CH2Cl2 (50 mL*3). The combined organics were concentrated under reduced pressure to give crude product, which was washed with EtOAc to give pure 3'-amino-N-methylbiphenyl-4-sulfonamide (C-3) (1.3 g, 50%). 1H NMR (300 MHz, CDCl3) delta 7.85 (d, J=8.7 Hz, 2H), 7.75 (d, J=8.7 Hz, 2H), 7.19 (t, J=7.8 Hz, 1H), 6.95-7.01 (m, 2H), 6.73-6.77 (m, 1H), 2.54 (s, 3H). MS (ESI) m/e (M+H+) 263.0.
	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; N,N-dimethyl-formamide; at 80℃;Inert atmosphere;	To a solution of 4-bromo-N-methyl-benzene sulfonamide (2.49 g, 10 mmol) in DMF (20 mL) was added 3-amino-phenyl boronic acid (1.51 g, 11 mmol), Pd(PPh3)4 (90 mg, 0.30 mmol), potassium carbonate (1.52 g, 11 mmol) and water (5 mL). The resulting mixture was degassed by gently bubbling argon through the solution for 5 minutes at 20 C. The reaction mixture was then heated at 80 C. overnight. The reaction was filtered through a pad of silica gel, which was washed with CH2Cl2 (50 mL*3). The combined organics were concentrated under reduced pressure to give crude product, which was washed with EtOAc to give pure 3'-amino-N-methylbiphenyl-4-sulfonamide (C-3) (1.3 g, 50%). 1H NMR (300 MHz, CDCl3) 7.85 (d, J=8.7 Hz, 2H), 7.75 (d, J=8.7 Hz, 2H), 7.19 (t, J=7.8 Hz, 1H), 6.95-7.01 (m, 2H), 6.73-6.77 (m, 1H), 2.54 (s, 3H). MS (ESI) m/e (M+H+) 263.0.

Reference： [1]Patent: US2008/9524,2008,A1 .Location in patent: Page/Page column 390
[2]Patent: US2011/98311,2011,A1
[3]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 1161

11
[ 74-89-5 ]
[ 98-58-8 ]
[ 703-12-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	In tetrahydrofuran; ethanol; at 20℃; for 0.0833333h;	Example 13: 5-(4-[(Methylamino)sulfonyliphenyl)-2-(2-phenylethyl) pentanoic acida) Synthesis of 4-Bromo-lambda/-methylbenzenesulfonamide. MeNH2 (7.5 ml, 8 M solution in EtOH, 60 mmol) was added to a solution of 4- bromobenzenesulfonyl chloride (5.0 g, 19.568 mmol) in THF (120 ml). The reaction mixture was stirred at room temperature for 5 min, poured into NH4CI (saturated aqueous solution, 300 ml) and extracted with EtOAc (500 ml). The <n="32"/>organic layer was dried over Na2SO4 (anhydrous), filtered and concentrated, to furnish 4-bromo-W-methylbenzenesulfonamide, which was submitted to next step without further purification (4.60 g, white solid, yield: 94%). 1H NMR (CDCI3, 250 MHz) delta ppm: 7.70 (m, 4H), 4.49 (bs, 1 H), 2.67 (d, J = 5.2 Hz, 3H).
94%	In tetrahydrofuran; dichloromethane; at 0 - 20℃; for 2h;Inert atmosphere;	To a stirred solution of 4-bromobenzene-l-sulfony chloride (BY; 2.5 g, 9.78 mmol) in CH2CI2 (20 mL) under inert atmosphere was added 2M methylamine in THF (10 mL, 19.56 mmol) at 0 C. The reaction was then warmed to RT and stirred for 2 h. After complete consumption of the starting material, the volatiles were evaporated under reduced pressure. The residue was neutralized with saturated sodium bicarbonate solution (30 mL) and the compound was extracted with CH2CI2 (3x25 mL). The combined organic extracts were washed with water (30 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude. The crude was triturated with diethyl ether/pentane (3x15 mL) to afford BZ (2 g, 94%) as a white solid. *H NMR (500 MHz, DMSO-i: delta 7.83 (d, J = 8.5 Hz, 2H), 7.70 (d, J = 8.5 Hz, 2H), 7.54 (s, 1H), 2.41 (d, / = 13.5 Hz, 3H). MS (ESI): m/z 250 [M+l]+
92%	In tetrahydrofuran; dichloromethane; at 0 - 20℃; for 18h;	To a solution of 4-bromobenzene-1-sulfonyl chloride (3 g, 11.74 mmol) in DCM (20 mL) at 0C was added methylamine (29 mL of a 2M solution in THF, 58.7 mmol) and the reaction mixture and stirred at room temperature for 18 hours. The reaction mixture was diluted with DCM (100 mL) and washed with ammonium chloride solution (20 mL). The organic layer was collected and dried overmagnesium sulfate, filtered and concentrated in vacuo. The resulting emulsion was purified by silica gel chromatography eluting with 0-40% Heptane: ethyl acetate to yield the desired compound as a white solid (2.7 g, 92% yield). ?H NMR (250 MHz, DMSO-d6) 7.91 - 7.79 (m, 2H), 7.79 - 7.65 (m, 2H), 7.56 (s, 1H), 2.43 (s, 3H).

87%	With pyridine; dmap; In tetrahydrofuran; at 20℃; for 0.25h;	To a solution of 4-bromobenzenesulfonyl chloride (1, 2.52 g, 9.86 mmol) in tetrahydrofuran (49.3 mL) was added methylamine (14.8 mL, 29.6 mmol) 2M in THF. The reaction mixture was stirred at RT for 15 min, poured into NH4Cl solution and extracted with EtOAc. The organic layer was dried over Na2SO4, concentrated and triturated with n-hexane to furnish 4- bromo-N-methylbenzenesulfonamide (2.15 g, 8,6 mmol, 87% yield) (0776) Analytical data: (0777) 1H NMR (200 MHz, CDCl3) delta 7.77- 7.59 (m, 1H), 5.03 (dd, J = 10.0, 4.9 Hz, 1H), 2.62 (d, J = 5.2 Hz, 1H); (0778) 13C NMR (50 MHz, CDCl3) delta 137.8, 132.5, 128.9, 127.8, 29.3; [M-1]- = 247.8.
82%	In tetrahydrofuran; dichloromethane; at 20℃; for 1h;	To synthesize compound 67, to a solution of 4-bromosulfonyl chloride (5.0 g, 20 mmol) in DCM (30 mL) was added methyl amine (2 M in THF, 20 mL, 40 mmol). The mixture was stirred at room temperature for 1 h and then the solvent was removed. A saturated NaHCO3 solution was added to the residue and then extracted with EtOAc. The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated and the residue triturated in hexane. Compound 67 was obtained as a white solid after filtration (4.0 g, 82%). 1H NMR (DMSO-d6): delta 2.41 (d, J=5.0 Hz, 3H), 7.56 (q, J=4.9 Hz, 1H), 7.70 (d, J=8.7 Hz, 2H), 7.83 (d, J=8.7 Hz, 2H).
28%	In ethanol; for 16h;Sealed tube;	4-Bromobenzene sulfonyl chloride (0.40 g, 1.56 mmol) and methylamine (10 mL, 33% in ethanol) were stirred in a sealed tube for 16 hours. The reaction mixture was concentrated in vacuo onto the Celite reagent. The crude product was purified via Isco chromatography (the Redisep column, silica, gradient 0-3% ethyl acetate-dichloromethane) to provide 4-bromo-N-methylbenzenesulfonamide (0.11 g, 28%). MS (ESI) m/z 250. High performance liquid chromatography (HPLC) purity 100.0% at 210-370 nm, 7.4 min.; the Xterra RP18 column, 3.5mu, 150*4.6 mm column, 1.2 mL/min., 85/15-5/95 (ammonium formate buffer pH=3.5/Acetonitrile (ACN)+MeOH) for 10 min., hold 4 min.
	With triethylamine; In tetrahydrofuran; at 20℃; for 37h;	Add a solution OF 4-BROMO-BENZENESULFONYL chloride (5.0 g, 19.2 mmol) in 10 mL THF at r. t. to a solution of methylamine (9.6 ml, 2 M in THF, 19.2 mmol) and triethylamine (2.72 mL, 19.2 mmol) over a period of 60 min and stir for 18 h. Add further methylamine (9.6 ml, 2 M in THF, 19.2 mmol) and triethylamine (2.72 mL, 19.2 mmol) and stir for 18 h. Evaporate the solvent under vacuum and add dichloromethane. Wash the organic layer with saturated aqueous sodium bicarbonate solution, followed by saturated sodium chloride solution. Filter through a hydrophobic filter paper and remove the solvent under vacuum. Further purify this material via column chromatography on silica gel, eluting with a gradient of 0-50 % ethyl acetate in hexane to afford the title compound (3.75 g) as a white solid. MS (m/e): 251 (M+H).
	With sodium hydrogencarbonate; In methanol; dichloromethane; water; at 20℃;	Step a: 4-Bromo-iV-methyl-benzenesulfonamide; To a mixture of sat aq. NaHCO3 (42 g, 0.5 mol), CH2Cl2 (400 mL) and methylamine (51.7 g, 0.5 mol, 30% in methanol) was added a solution of 4-bromo-benzenesulfonyl chloride (127 g, 0.5 mol) in CH2Cl2 (100 mL). The reaction was stirred at 20 0C overnight. The organic phase was separated and dried over Na2SO4. Evaporation of the solvent under reduced pressure provided the 4-bromo-iV-methyl-benzenesulfonamide (121 g, crude), which was used in the next step without further purification. 1H NMR (CDCl3, 300 MHz) delta 7.64-7.74 (m, 4 H), 4.62-4.78 (m, 1 H), 2.65 (d, J = 5.4 Hz, 3 H).
	With sodium hydrogencarbonate; In dichloromethane; at 20℃;	Step a: 4-Bromo-N-methyl-benzenesulfonamide To a mixture of sat aq. NaHCO3 (42 g, 0.50 mol), CH2Cl2 (400 mL) and methylamine (51.7 g, 0.50 mol, 30% in methanol) was added a solution of 4-bromo-benzenesulfonyl chloride (130 g, 0.50 mol) in CH2Cl2 (100 mL). The reaction was stirred at 20 C. overnight. The organic phase was separated and dried over Na2SO4. Evaporation of the solvent under reduced pressure provided 4-bromo-N-methyl-benzenesulfonamide (121 g, crude), which was used in the next step without further purification. 1H NMR (CDCl3, 300 MHz) delta 7.65-7.74 (m, 4H), 4.40 (br, 1H), 2.67 (d, J=5.4 Hz, 3H).
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 16h;	Example 17; 239 242 243Part A:To a solution of compound 239 (1.00 g, 3.91 mmol) in dichloromethane (20 mL) was added diisopropylethylamine (0.75 ml_, 4.30 mmol) at room temperature. The reaction mixture was cooled to O0C (ice-bath) and the corresponding amine (1.1 equivalents) to make a compound in Table 20 was added. The reaction mixture was allowed to warm to room temperature, stirred at ambient temperature for 16 hours, at which time LC-MS analysis indicated that the reaction was complete. The reaction mixture was concentrated under vacuum. Purification of by column chromatography ((SiO2, 2% ethyl acetate / dichloromethane) afforded compound of general formula 242 as a solid.
	With pyridine; In dichloromethane; at 20℃; for 16h;	Example 40 : N-Methyl-4-(6-( 1 -methyl- 1 H-pyrazo 1-4-ylamino)- 1 H-pyrazo lo [3 ,4- d]pyrimidin- 1 -yl)benzenesulfonamideThe following compound was made according to the procedure in Example 17 (step iii), using 4-bromo-N-methylbenzenesulfonamide as alkylating agent:4-bromo-N-methylbenzenesulfonamide was prepared by stirring a solution of 4- bromobenzenesulfonyl chloride (400mg, 1.57mmol), methylamine (0.78mL, 2M solution in THF) and pyridine (lmL) in dichloromethane (5mL) was at rt for 16h. The mixture was then diluted with dichloromethane and washed with H20 and then brine. The organic phase was collected, dried (MgS04) and concentrated in vacuo to give 4-bromo-N- methylbenzenesulfonamide. 1H NMR (d6-DMSO) delta 10.12 (s, 1H0, 9.04 (s, 1H), 8.45 (d, 2H), 8.38 (s, 1H), 8.00 (d, 2H), 7.96 (s, 1H), 7.64 (s, 1H), 7.57 (s, 1H), 3.87 (s, 3H), 2.47 (s, 3H); LC-MS method B, (ES+) 385.0, RT = 7.45min.
1.80 g	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; dichloromethane; at 0℃; for 0.166667h;	To a stirring solution of 4-bromobenzenesulfonyl chloride (2.0 g, 7.8 mmol, Sigma-Aldrich, St. Louis, MO) and DIEA (1.50 mL, 8.61 mmol) in CH2C12 (25 mL) at 0 C, was added methanamine (2 M in THF, 7.83 mL, 15.7 mmol, Sigma-Aldrich, St. Louis, MO). After 10 min, the reaction mixture was treated with 1 M KH2P04 (50 mL). The organic was concentrated under reduced pressure and then purified by silica gel chromatography (0 to 4% of MeOH/CH2Cl2) to afford 4-bromo-N-methylbenzenesulfonamide (1.80 g) as a white solid.
	With sodium hydrogencarbonate; In methanol; dichloromethane; at 20℃;	To a mixture of sat aq. NaHCO3 (42 g, 0.50 mol), CH2Cl2 (400 mL) and methylamine (51.7 g, 0.50 mol, 30% in methanol) was added a solution of 4-bromo-benzenesulfonyl chloride (130 g, 0.50 mol) in CH2Cl2 (100 mL). The reaction was stirred at 20 C. overnight. The organic phase was separated and dried over Na2SO4. Evaporation of the solvent under reduced pressure provided 4-bromo-N-methyl-benzenesulfonamide (121 g, crude), which was used in the next step without further purification. 1H NMR (CDCl3, 300 MHz) delta7.65-7.74 (m, 4H), 4.40 (br, 1H), 2.67 (d, J=5.4 Hz, 3H).
	With sodium hydrogencarbonate; In dichloromethane; water; at 20℃; for 0.5h;	(Example 38) 3'-[2-Isopropyl-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl]-N-methyl-1,1'-biphenyl-4-sulfonamide (Compound No. 1-379) Saturated aqueous sodium bicarbonate (3 mL) and a 40% methylamine aqueous solution (1 mL, 13 mmol) were added to a solution of 4-bromobenzenesulfonyl chloride (0.26 g, 1.0 mmol) in methylene chloride (5 mL). The resulting mixture was stirred at room temperature for 30 min. Water and methylene chloride were added to the reaction solution, and the organic layer was extracted using an Empore cartridge (GL Science). The compound (0.12 g, 0.48 mmol) obtained by evaporating the solvent under reduced pressure, 2- {2-isopropyl-5-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1H-imidazol-4-yl}-6-methylpyridine (0.12 g, 0.30 mmol) obtained in Example (35a), tripotassium phosphate n-hydrate (0.19 g, 0.72 mmol), and dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane complex (25 mg, 0.030 mmol) were dissolved in 1,2-dimethoxyethane (3 mL). The resulting mixture was stirred at 80C for 3 hr. The reaction mixture was diluted with ethyl acetate and filtered through silica gel. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by high-performance liquid chromatography (GL Science ODS-3, eluding solvent; water: acetonitrile = 95: 5 to 5: 95) to obtain 60 mg (yield: 45%) of the title compound as a white amorphous form. Melting point: 96 to 100C. 1H-NMR (500 MHz, CDCl3) delta ppm: 10.72 (1H, brs), 7.86-7.84 (3H, m), 7.72-7.65 (3H, m), 7.53 (1H, m), 7.49 (1H, m), 7.41 (1H, t, J = 7.8 Hz), 7.29 (1H, d, J = 7.8 Hz), 6.96 (1H, d, J = 7.3 Hz), 4.82 (1H, brs), 3.17 (1H, m), 2.65 (3H, s), 2.48 (3H, s), 1.38 (6H, d, J = 7.3 Hz). MS(ES) m/z: 447 (M + H)+.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3880 - 3885
[2]Patent: WO2009/80722,2009,A2 .Location in patent: Page/Page column 30-31
[3]Patent: WO2014/117090,2014,A1 .Location in patent: Page/Page column 130
[4]Patent: WO2017/70081,2017,A1 .Location in patent: Page/Page column 190
[5]Patent: WO2019/149738,2019,A1 .Location in patent: Page/Page column 73; 74
[6]Chemistry - A European Journal,2017,vol. 23,p. 14345 - 14357
[7]Patent: US2005/245524,2005,A1 .Location in patent: Page/Page column 80
[8]Patent: US2008/221201,2008,A1 .Location in patent: Page/Page column 8
[9]Patent: WO2004/63179,2004,A1 .Location in patent: Page 93
[10]Patent: WO2007/56341,2007,A1 .Location in patent: Page/Page column 158
[11]Patent: US2008/9524,2008,A1 .Location in patent: Page/Page column 390
[12]Journal of Organic Chemistry,2008,vol. 73,p. 2428 - 2431
[13]Patent: WO2008/82487,2008,A2 .Location in patent: Page/Page column 115
[14]Organic Letters,2011,vol. 13,p. 1556 - 1559
[15]Patent: WO2011/48082,2011,A1 .Location in patent: Page/Page column 85
[16]Patent: WO2014/35872,2014,A1 .Location in patent: Page/Page column 134
[17]Journal of Medicinal Chemistry,2014,vol. 57,p. 3094 - 3116
[18]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 1160
[19]Organic Letters,2016,vol. 18,p. 2280 - 2283
[20]Patent: EP1798229,2007,A1 .Location in patent: Page/Page column 108
[21]Organic Letters,2017,vol. 19,p. 5844 - 5847
[22]Chemical Communications,2018,vol. 54,p. 8403 - 8406
[23]Archiv der Pharmazie,2019,vol. 352

12
[ 703-12-8 ]
[ 226396-31-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3880 - 3885

13
[ 703-12-8 ]
[ 68502-14-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3880 - 3885

14
[ 703-12-8 ]
C₁₅H₁₃N₃O₄S₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3880 - 3885

15
[ 703-12-8 ]
(N-methyl-4-bromobenzenesulfonamido)methyl (2S,5R,6R)-1-aza-3,3-dimethyl-7-oxo-6-phenylacetamido-4-thiabicyclo[3.2.0]heptane-2-carboxylate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2000,vol. 8,p. 1629 - 1636

16
[ 703-12-8 ]
C₁₅H₁₄BrNO₂S [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1974,vol. 39,p. 3219 - 3223

17
[ 703-12-8 ]
[ 52260-09-0 ]

Reference： [1]Journal of Organic Chemistry,1974,vol. 39,p. 3219 - 3223

18
[ 731017-13-3 ]
[ 703-12-8 ]
[ 731018-65-8 ]

Yield	Reaction Conditions	Operation in experiment
	With cesium fluoride;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 60℃; for 4h;	Heat a suspension OF 4-BROMO-N METHYL-BENZENESULFONAMIDE (0.51 g, 2.0 mmol), (E)-3- cyclohexyl-2- (4, 4,5, 5-TETRAMETHYL- [1, 3,2] dioxaborolan-2-yl)-prop-2-en-1-ol (0.81 g, 3.06 mmol), caesiumfluoride (0.93 g, 6.12 mmol) and tetrakis (triphenylphosphino) PALLADIUM (0) (230 mg, 0.2 mmol) in 12 mL THF to 60 C for 4 h. Remove the solvent under vacuum and add ethyl acetate, wash the organic layer with water followed by saturated sodium chloride solution. Filter through a hydrophobic filter paper and remove the solvent under vacuum. Further purify the resulting residue by column chromatography, eluting with a gradient from 100: 0 to 35: 65 hexanes: ethyl acetate to afford the title compound (0.51 g) as a gray solid. MS (m/e): 310 (M+H).

Reference： [1]Patent: WO2004/63179,2004,A1 .Location in patent: Page 93-94

19
[ 3240-94-6 ]
[ 703-12-8 ]
[ 867332-77-2 ]

Yield	Reaction Conditions	Operation in experiment
83%	With caesium carbonate; In acetonitrile; for 15h;Heating / reflux;	To synthesize compound 68, a solution of compound 67 (1.0 g, 4.0 mmol), 4-(2-chloro-ethyl)-morpholine (0.85 g, 4.6 mmol) and cesium carbonate (3.3 g, 10 mmol) in acetonitrile (30 mL) was heated at reflux for 15 h. The mixture was cooled and poured into water. The aqueous layer was extracted with EtOAc and the combined organic layers washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated and the residue triturated in Et2O/hexane (1/1) to afford compound 68 as an off-white solid (1.2 g, 83%) after filtration. MS (ESI+): m/z 363

Reference： [1]Patent: US2005/245524,2005,A1 .Location in patent: Page/Page column 80

Yield	Reaction Conditions	Operation in experiment
		According to Method C1a, 4-chloro-3-(trifluoromethyl)phenyl isocyanate was reacted with 4-(4-methylsulfonylphenoxy)-1-aniline to afford the urea. Entry 54: 4-Bromobenzenesulfonyl chloride was reacted with methylamine according to Method A15, Step 1 to afford N-methyl-4-bromobenzenesulfonamide.
		According to Method C1a, 4-chloro-3-(trifluoromethyl)phenyl isocyanate was reacted with 4-(4-methylsulfonylphenoxy)-1-aniline to afford the urea. Entry 54: 4-Bromobenzenesulfonyl chloride was reacted with methylamine according to Method A15, Step 1 to afford N-methyl-4-bromobenzenesulfonamide.
		According to Method C1a, 4-chloro-3-(trifluoromethyl)phenyl isocyanate was reacted with 4-(4-methylsulfonylphenoxy)-1-aniline afford the urea. Entry 54: 4-Bromobenzenesulfonyl chloride was reacted with methylamine according to Method A15, Step 1 to afford N-methyl-4-bromobenzenesulfonamide.

21
[ 703-12-8 ]
[ 824-94-2 ]
[ 158425-24-2 ]

Yield	Reaction Conditions	Operation in experiment
3.6 g (97%)	In NaH; N,N-dimethyl-formamide;	(b) N-Methyl-N-(4-methoxybenzyl)-4-bromophenylsulfonamide To a solution of N-methyl-4-bromophenylsulfonamide (2.5 g, 10 mmol) in DMF (20 mL) at room temperature was added in portions NaH (264 rag, 11 mmol). The mixture was stirred for 45 minutes and then p-methoxybenzylchloride (1.49 mL, 11 mmol) was added dropwise. The mixture was stirred for 1 hour, quenched with water and the precipitate which formed was collected by filtration and dried in vacuo at 60 C. to afford 3.6 g (97%) of N-methyl-N-(4-methoxybenzyl)-4-bromophenylsulfonamide.

Reference： [1]Patent: US5380721,1995,A

22
[ 98-58-8 ]
[ 703-12-8 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; methylamine; In dichloromethane;	(a) N-Methyl-4-bromophenyl sulfonamide A mixture of 4-bromophenylsulfonyl chloride (25.5 g, 100 mmol), CH2 Cl2 (400 mL) and pyridine (1.6 g, 110 mol) was cooled to 0 C. and methylamine gas was added over 45 minutes. The mixture was warmed to room temperature, the solvent was removed in vacuo and the residue was dissolved in CH2 Cl2 and washed with 2N HCl (2100 mL), water (1200 mL), saturated NaHCO3 (1200 mL) and then brine (1200 mL). The solvent was dried over MgSO4 and the solvent was removed in vacuo to afford 23 g of N-methyl-4-bromophenylsulfonamide.
	With methylamine; In methanol; dichloromethane;	Step a: 4-Bromo-N-methyl-benzenesulfonamide To a mixture of sat aq. NaHCO3 (42 g, 0.50 mol), CH2Cl2 (400 mL) and methylamine (51.7 g, 0.50 mol, 30% in methanol) was added a solution of 4-bromo-benzenesulfonyl chloride (130 g, 0.50 mol) in CH2Cl2 (100 mL). The reaction was stirred at 20 C. overnight. The organic phase was separated and dried over Na2SO4. Evaporation of the solvent under reduced pressure provided 4-bromo-N-methyl-benzenesulfonamide (121 g, crude), which was used in the next step without further purification. 1H NMR (CDCl3, 300 MHz) delta 7.65-7.74 (m, 4H), 4.40 (br, 1H), 2.67 (d, J=5.4 Hz, 3H).

Reference： [1]Patent: US5380721,1995,A
[2]Patent: US2011/98311,2011,A1
[3]Journal of Fluorine Chemistry,2016,vol. 188,p. 65 - 75
[4]Journal of Fluorine Chemistry,2016,vol. 188,p. 65 - 75

23
(3-chlorophenyl)-1,3-dichloro 2-propanol [ No CAS ]
[ 703-12-8 ]
[ 1643-19-2 ]
[ 117795-90-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In toluene;	REFERENCE EXAMPLE 8 Preparation of 4-bromo-N [2 (3-chlorophenyl).2,3-epoxypropyl]-N-methylbenzenesulfonamide To a mixture of 2.0 g of <strong>[703-12-8]4-bromo-N-methyl benzenesulfonamide</strong>, 1.9 g of 2 (3-chlorophenyl)-1,3-dichloro 2-propanol, 0.05 g of tetra.n.butylammonium bromide and 5 ml of toluene, was added 5 ml of 40% aqueous sodium hydroxide. The mixture was stirred at 80 C. for 7 hours. After cooling, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated under a reduced pressure. The residue was purified by silica gel column chromatography (developing solvent:ethyl acetate -n-hexane) to obtain 1.02 g of the intended compound. IR spectrum (KBr) cm-1: 3070, 1340, 1165, 1155. 1 H--NMR spectrum (CDCl4 --TMS)delta: 2.76 (3H, s), 2.76 (1H, d), 3.06 (1H, d), 3.09 (1H, d), 4.12 (1H, d), 7.15 to 7.50 (4H, m), 7.67 (4H, s).

Reference： [1]Patent: US4971620,1990,A

24
[ 117795-04-7 ]
[ 703-12-8 ]
[ 117795-90-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; tetrabutylammomium bromide; In toluene;	Reference Example 8 Preparation of 4-bromo-N-[2-(3-chlorophenyl)-2,3-epoxypropyl]-N-methylbenzenesulfonamide To a mixture of 2.0 g of <strong>[703-12-8]4-bromo-N-methylbenzenesulfonamide</strong>, 1.9 g of 2-(3-chlorophenyl)-1,3-dichloro-2-propanol, 0.05 g of tetra-n-butylammonium bromide and 5 ml of toluene, was added 5 ml of 40% aqueous sodium hydroxide. The mixture was stirred at 80C for 7 hours. After cooling, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated under a reduced pressure. The residue was purified by silica gel column chromatography developing solvent: ethyl acetate &horbar; n-hexane) to obtain 1.02 g of the intended compound. IR spectrum (KBr) cmmin1: 3070, 1340, 1165, 1155 1H-NMR spectrum (CDCl4-TMS)delta: 2.76 (3H, s), 2.76 (1H, d), 3.06 (1H, d), 3.09 (1H, d), 4.12 (1H, d), 7.15 to 7.50 (4H, m), 7.67 (4H, s)

Reference： [1]Patent: EP326170,1991,B1

25
[ 879486-04-1 ]
[ 703-12-8 ]
3'-[2-Isopropyl-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl]-N-methyl-1,1'-biphenyl-4-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,2-dimethoxyethane; at 80℃; for 3h;	(Example 38) 3'-[2-Isopropyl-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl]-N-methyl-1,1'-biphenyl-4-sulfonamide (Compound No. 1-379) Saturated aqueous sodium bicarbonate (3 mL) and a 40% methylamine aqueous solution (1 mL, 13 mmol) were added to a solution of 4-bromobenzenesulfonyl chloride (0.26 g, 1.0 mmol) in methylene chloride (5 mL). The resulting mixture was stirred at room temperature for 30 min. Water and methylene chloride were added to the reaction solution, and the organic layer was extracted using an Empore cartridge (GL Science). The compound (0.12 g, 0.48 mmol) obtained by evaporating the solvent under reduced pressure, 2- {2-isopropyl-5-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1H-imidazol-4-yl}-6-methylpyridine (0.12 g, 0.30 mmol) obtained in Example (35a), tripotassium phosphate n-hydrate (0.19 g, 0.72 mmol), and dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane complex (25 mg, 0.030 mmol) were dissolved in 1,2-dimethoxyethane (3 mL). The resulting mixture was stirred at 80C for 3 hr. The reaction mixture was diluted with ethyl acetate and filtered through silica gel. The filtrate was concentrated under reduced pressure, and the resulting crude product was purified by high-performance liquid chromatography (GL Science ODS-3, eluding solvent; water: acetonitrile = 95: 5 to 5: 95) to obtain 60 mg (yield: 45%) of the title compound as a white amorphous form. Melting point: 96 to 100C. 1H-NMR (500 MHz, CDCl3) delta ppm: 10.72 (1H, brs), 7.86-7.84 (3H, m), 7.72-7.65 (3H, m), 7.53 (1H, m), 7.49 (1H, m), 7.41 (1H, t, J = 7.8 Hz), 7.29 (1H, d, J = 7.8 Hz), 6.96 (1H, d, J = 7.3 Hz), 4.82 (1H, brs), 3.17 (1H, m), 2.65 (3H, s), 2.48 (3H, s), 1.38 (6H, d, J = 7.3 Hz). MS(ES) m/z: 447 (M + H)+.

Reference： [1]Patent: EP1798229,2007,A1 .Location in patent: Page/Page column 108

26
[ 5419-55-6 ]
[ 703-12-8 ]
[ 226396-31-2 ]

Yield	Reaction Conditions	Operation in experiment
96%		Step b: 4-(lambdar-Methylsulfamoyl)phenylboronic acid; To a solution of 4-bromo-iV-methyl-benzene sulfonamide (24.9 g, 0.1 mol) and B(O1Pr)3 (28.2 g, 0.15 mol) in THF (200 mL) was added n-BuLi (100 mL, 0.25 mol) at -70 0C. The mixture was slowly warmed to 0 0C, then 10% HCl solution was added until pH 3-4. The resulting mixture was extracted with EtOAc. The organic layer was dried over Na2SO4, and evaporated under reduced pressure to give 4-(iV-methylsulfamoyl)phenylboronic acid (22.5 g, 96%), which was used in the next step without further purification. 1H NMR (DMSO-J6, 300 MHz) delta 8.29 (s, 2 H), 7.92 (d, J = 8.1 Hz, 2 H), 7.69 (d, J = 8.4 Hz, 2 H), 2.36 (d, J = 5.1 Hz, 3 H).
21%	With n-butyllithium; In tetrahydrofuran; at -70 - 0℃;	To a solution of <strong>[703-12-8]4-bromo-N-methylbenzenesulfonamide</strong> (2, 1.05 g, 4.20 mmol) and triisopropyl borate (1.45 mL, 6.30 mmol) in tetrahydrofuran (8.40 mL) was added n-Butyl Lithium (4.20 mL, 10.5 mmol) at -70 C. The mixture was slowly warmed to 0 C, then 10% HCl solution was added until pH 3-4. The resulting mixture was extracted with EtOAc. The organic layer was extracted with NaOH (2M) and the aqueous phase washed with diethyl ether. The aqueous phase was acidified to pH 3, extracted with EtOAc (impurities and unconsumed reactant were still present) was dried over Na2SO4, and evaporated under reduced pressure. The residue was triturated with diethyl ether to give [4- (methylsulfamoyl)phenyl]boronic acid (187 mg, 0,8700 mmol, 21% yield). (0781) Analytical data: (0782) 1H NMR (200 MHz, DMSO) delta 7.96 (d, J = 8.1 Hz, 2H), 7.72 (d, J = 8.0 Hz, 2H), 7.42 (q, J = 4.9 Hz, 1H), 2.39 (d, J = 5.0 Hz, 3H); (0783) 13C NMR (50 MHz, DMSO) delta 140.6, 134.8, 125.7, 28.8.

Reference： [1]Patent: WO2007/56341,2007,A1 .Location in patent: Page/Page column 158
[2]Patent: WO2019/149738,2019,A1 .Location in patent: Page/Page column 73; 74

27
[ 860617-71-6 ]
[ 703-12-8 ]
[ 1055994-54-1 ]

Yield	Reaction Conditions	Operation in experiment
25%	With potassium fluoride;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In tetrahydrofuran; hexane; for 16h;	4-Bromo-N-methylbenzenesulfonamide (100 mg, 0.40 mmol), 5-cyano-1-methyl-1H-pyrrol-2-ylboronic acid (72 mg, 0.48 mmol), potassium fluoride (76 mg, 1.3 mmol), and tris(dibenzylideneacetone)dipalladium(0) (10 mg, 0.01 mmol) were placed in an oven dried flask under nitrogen and dry THF (1.0 mL) was added. Tri-t-butylphosphine (60 muL, 0.02 mmol, 10 wt % in hexane) was added and the reaction was stirred for 16 hours. The reaction mixture was filtered through silica and rinsed with ethyl acetate. The solvent was concentrated in vacuo to provide the crude product. The crude product was pre-adsorbed onto the Celite reagent and purified via Isco chromatography (the Redisep column, silica, gradient 5-50% ethyl acetate in hexane) to afford 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-methylbenzenesulfonamide (28 mg, 25%). MS (ESI) m/z 275. HPLC purity 100.0% at 210-370 nm, 9.0 min.; the Xterra RP18 column, 3.5mu, 150*4.6 mm column, 1.2 mL/min., 85/15-5/95 (ammonium formate buffer pH=3.5/ACN+MeOH) for 10 min., hold 4 min.

Reference： [1]Patent: US2008/221201,2008,A1 .Location in patent: Page/Page column 8

28
[ 24424-99-5 ]
[ 703-12-8 ]
[ 1166182-12-2 ]

Yield	Reaction Conditions	Operation in experiment
98%	With dmap; N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 0.5h;	b) Synthesis of tert-butyl (4-bromophenyl)sulfonyl(methyl)carbamate. BoC2O (4.711 g, 21.589 mmol) was added to a solution of 4-bromo-/V- methylbenzenesulfonamide (4.5 g, 17.99 mmol), DMAP (329 mg, 2.698 mmol) and DIPEA (9.25 ml, 53.97 mmol) in CH3CN (100 ml). The reaction mixture was stirred at room temperature for 30 min, poured into H2O (200 ml) and extracted with EtOAc (200 ml). The organic layer was dried over Na2SO4 (anhydrous), filtered and concentrated. The crude residue was flash chromatographed on SiO2 (10?20% EtOAc/hexanes), to afford tert-butyl (4- bromophenyl)sulfonyl (methyl)carbamate (6.18 g, white solid, yield: 98%). 1H NMR (CDCI3, 250 MHz) delta ppm: 7.77 (d, J = 9.0 Hz, 2H), 7.66 (d, J = 9.0 Hz, 2H), 3.34 (s, 3H), 1.37 (s, 9H).

Reference： [1]Patent: WO2009/80722,2009,A2 .Location in patent: Page/Page column 31

29
[ 703-12-8 ]
[ 108-88-3 ]
[ 333434-62-1 ]

Reference： [1]Journal of Organic Chemistry,2010,vol. 75,p. 2726 - 2729

30
[ 703-12-8 ]
[ 1268824-78-7 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 1556 - 1559

31
[ 703-12-8 ]
[ 536-74-3 ]
[ 1268824-72-1 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 1556 - 1559

32
[ 703-12-8 ]
[ 945239-58-7 ]

Reference： [1]Patent: US2015/231142,2015,A1

33
[ 30418-59-8 ]
[ 703-12-8 ]
[ 945239-58-7 ]

Reference： [1]Patent: US2011/98311,2011,A1

34
[ 703-12-8 ]
[ 13139-86-1 ]
[ 1263277-92-4 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 5342 - 5345

35
[ 149105-19-1 ]
[ 703-12-8 ]
[ 1554492-74-8 ]

Yield	Reaction Conditions	Operation in experiment
74%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 150℃; for 0.333333h;Microwave irradiation;	2-Carboxybenzeneboronic acid (0.20g, 1.21mmol), 4-bromo-N- methylbenzenesulphonamide (0.36g, 1.45mmol), Na2CO3 (0.26g, 2.42mmol) and Pd(PPh3)4 (140mg, 0.12mmol) were suspended in dioxane/water (4mL, 1 : 1) and heated using a microwave reactor at 150C for 20min. The reaction mixture was concentrated in vacuo, dissolved in EtOAc (30mL) and washed with water (2x3 OmL). The combined aqueous fractions were acidified to pH 1 with 1M aq HC1 and extracted with EtOAc (2x30mL). The combined organic fractions were washed with brine (30mL), dried (MgS04) and concentrated in vacuo to give the title compound (259mg, 74%) as a white solid. LCMS: ES+ 292.0 [MH]+.
74%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 150℃; for 0.333333h;Microwave irradiation;	2-Carboxybenzeneboronic acid (0. 20g, 1.21 mmol), 4-bromo-N- methylbenzenesulphonamide (0.3 6g, 1. 4Smmol), Na2CO3 (0. 26g, 2. 42mmol) and Pd(PPh3)4 (140mg, 0.l2mmol) were suspended in dioxane/water (4mL, 1:1) and heated using a microwave reactor at 150C for 20mm. The reaction mixture was concentrated invacuo, dissolved in EtOAc (3OmL) and washed with water (2x3OmL). The combined aqueous fractions were acidified to pH 1 with 1M aq HC1 and extracted with EtOAc (2x3OmL). The combined organic fractions were washed with brine (3OmL), dried (MgSO4) and concentrated in vacuo to give the title compound (259mg, 74%) as a white solid. LCMS: ES 292.0 [IVIH]

Reference： [1]Patent: WO2014/20350,2014,A1 .Location in patent: Page/Page column 29
[2]Patent: WO2014/20351,2014,A1 .Location in patent: Page/Page column 15; 16

36
[ 703-12-8 ]
C₁₄H₁₉N₃O₂S [ No CAS ]

Reference： [1]Patent: WO2014/35872,2014,A1
[2]Journal of Medicinal Chemistry,2014,vol. 57,p. 3094 - 3116

37
[ 703-12-8 ]
[ 1572928-42-7 ]

Reference： [1]Patent: WO2014/35872,2014,A1
[2]Journal of Medicinal Chemistry,2014,vol. 57,p. 3094 - 3116

38
[ 703-12-8 ]
[ 1572927-69-5 ]

Reference： [1]Patent: WO2014/35872,2014,A1
[2]Journal of Medicinal Chemistry,2014,vol. 57,p. 3094 - 3116

39
[ 703-12-8 ]
[ 1572927-69-5 ]
[ 1572927-70-8 ]

Reference： [1]Patent: WO2014/35872,2014,A1

40
[ 703-12-8 ]
[ 1572928-44-9 ]

Reference： [1]Patent: WO2014/35872,2014,A1

41
[ 703-12-8 ]
[ 1572928-45-0 ]

Reference： [1]Patent: WO2014/35872,2014,A1

42
[ 1450620-13-9 ]
[ 703-12-8 ]
[ 1572928-41-6 ]

Yield	Reaction Conditions	Operation in experiment
235 mg	With chloro(2-dicyclohexylphosphino-2?,6?-di-i-propoxy-1,1?-biphenyl)(2?-amino-1,1?-biphenyl-2-yl)-palladium(II); sodium t-butanolate; ruphos; In 1,4-dioxane; at 100℃; for 0.75h;Inert atmosphere;	A suspension of benzyl (3S)-3-(l-propyn-l-yl)-l-piperazinecarboxylate (1000 mg, 3.87 mmol, Intermediate E), <strong>[703-12-8]4-bromo-N-methylbenzenesulfonamide</strong> (1450 mg, 5.81 mmol), RuPhos palladacycle (158 mg, 0.194 mmol, Strem Chemicals, Newburyport, MA), RuPhos (90.0 mg, 0.194 mmol, Strem Chemicals, Newburyport MA), sodium tert-butoxide (930 mg, 9.68 mmol, Sigma-Aldrich, St. Louis, MO) in 1,4-dioxane (10 mL) was sparged with argon for 1 min then heated to 100 C. After 45 min, the reaction mixture was partitioned between EtOAc (50 mL) and 5% NaHC03 (20 mL). The organic was dried over MgS04, filtered and concentrated under reduced pressure then purified by silica gel chromatography (80 g, 10 to 70% EtOAc in hexanes)to afford benzyl (3 S)-4-(4-(methylsulfamoyl)phenyl)-3 -( 1 -propyn- 1 -yl)- 1 - piperazinecarboxylate (235 mg) as an amber oil.

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 3094 - 3116
[2]Patent: WO2014/35872,2014,A1 .Location in patent: Page/Page column 134-135

43
[ 1361224-50-1 ]
[ 703-12-8 ]
[ 1572928-43-8 ]

Yield	Reaction Conditions	Operation in experiment
400 mg	With chloro(2-dicyclohexylphosphino-2?,6?-di-i-propoxy-1,1?-biphenyl)(2?-amino-1,1?-biphenyl-2-yl)-palladium(II); sodium t-butanolate; ruphos; In 1,4-dioxane; at 80℃; for 10h;Inert atmosphere;	In a 100-mL re-sealable reaction tube, benzyl 3-(l-propyn-l-yl)-l- piperazinecarboxylate (500 mg, 1.93 mmol, Intermediate E, Step 3) and 4- bromo-N-methylbenzenesulfonamide (482 mg, 1.93 mmol) were dissolved in 1,4-dioxane (30 mL) at rt. The solution was degassed by purging with argon gas at rt for 30 min. RuPhos (10 mg, 0.019 mmol, Sigma-Aldrich, India), RuPhos palladacycle (20 mg, 0.019 mmol, Sigma-Aldrich, India) and sodium tert- butoxide (560 mg, 5.79 mmol, Sigma-Aldrich, India) were added sequentially to the above solution at rt under argon atmosphere. The reaction tube was sealed under argon and the reaction mixture was heated at 80 C for 10 h. The reaction mixture was cooled to rt and filtered through a diatomaceous earth pad. The filtrate was diluted with cold water (20 mL) and ethyl acetate (50 mL). The organic layer was separated, washed with water and brine, dried over anhydrous Na2S04 and filtered. The filtrate was concentrated under reduced pressure and the crude residue obtained was purified by silica gel (60 to 120 mesh) column chromatography (eluent, 20% EtOAc-hexanes) to give benzyl 4-(4- (methylsulfamoyl)phenyl)-3 -( 1 -propyn- 1 -yl)- 1 -piperazinecarboxylate (400 mg) as a white solid.

Reference： [1]Patent: WO2014/35872,2014,A1 .Location in patent: Page/Page column 137-138

44
[ 703-12-8 ]
[ 1446402-54-5 ]

Reference： [1]Organic and Biomolecular Chemistry,2014,vol. 12,p. 6349 - 6353

45
[ 703-12-8 ]
[ 920-46-7 ]
[ 1620220-77-0 ]

Reference： [1]Organic and Biomolecular Chemistry,2014,vol. 12,p. 6349 - 6353
[2]Organic Letters,2017,vol. 19,p. 5844 - 5847

46
[ 703-12-8 ]
[ 1620955-72-7 ]

Reference： [1]Patent: WO2014/117090,2014,A1

47
[ 703-12-8 ]
[ 1620955-70-5 ]

Reference： [1]Patent: WO2014/117090,2014,A1

48
[ 703-12-8 ]
[ 1620955-71-6 ]

Reference： [1]Patent: WO2014/117090,2014,A1

49
[ 703-12-8 ]
[ 73183-34-3 ]
N-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 12h;Inert atmosphere;	To a stirred solution of BZ (500 mg, 2.00 mmol) in 1,4-dioxane (20 mL) under inert atmosphere were added bis(pinacalato)diboron (561 mg, 2.20 mmol) and fused potassium acetate (590 mg, 6.02 mmol) at RT. The reaction was purged with argon for 30 min. Then Pd(dppf)2Cl2 (146 mg, 0.2 mmol) was added to the reaction mixture and the reaction was heated to 100 C and stirred for 12 h. The reaction was monitored by TLC. After complete consumption of the starting material, the reaction mass was cooled to RT and filtered through a Celite pad. The filtrate was concentrated under reduced pressure to obtain the crude. The crude was purified by silica gel column chromatography (30-40% EtOAc/hexanes) to afford CA (400 mg, 67%) as a white solid. *H NMR (500 MHz, CDC13): delta 7.95 (d, J = 8.0 Hz, 2H), 7.84 (d, / = 8.5 Hz, 2H), 4.27 (d, / = 5.5 Hz, 1H), 2.65 (d, / = 5.5 Hz, 3H), 1.35 (s, 12H). MS (ESI): m/z 298 [M+l]+
45.70%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 16h;Inert atmosphere;	Step 3: Synthesis of 2-(4-(methylaminosulfonyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane To a stirred 1-bromo-4-(methylaminosulfonyl)benzene (0.22 g, 0.88 mmol) and Bispinacolatodiboron (0.27 g, 1.06 mmol) in Dioxane (7.0 mL), Potassium acetate (0.26 g, 2.65 mmol) was added and reaction mixture degassed with nitrogen gas for 30 min. Then to it, PdCl2(dppf) (0.033 g, 0.05 mmol) was added and allowed to stir at 100 C. for 16 h. Progress of reaction was monitored by TLC. On completion, Dioxane was evaporated from reaction mixture and residue quenched with water, compound was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure to give crude compound which was purified by Combi-flash column chromatography (4.0 g column); eluted in 15% ethyl acetate in hexane to give 2-(4-(methylaminosulfonyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.120 g,45.70%) as white solid. MS: 298.12 [M++1].

Reference： [1]Patent: WO2014/117090,2014,A1 .Location in patent: Page/Page column 130-131
[2]Patent: US2017/291910,2017,A1 .Location in patent: Paragraph 0433-0435

50
4-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole-5-carbonitrile [ No CAS ]
[ 703-12-8 ]
4-(3-cyano-4-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)-N-methylbenzenesulfonamide [ No CAS ]

Reference： [1]Organic Letters,2014,vol. 16,p. 6120 - 6123

51
[ 67-56-1 ]
[ 701-34-8 ]
[ 703-12-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	With [(Cp*IrCl)2(4,4',6,6'-tetrahydroxy-2,2'-bipyrimidine)][Cl]2; potassium hydroxide; In water; at 130℃; for 12h;	The p-bromobenzenesulfonamide (118.0mg, 0.5mmol), iridium catalyst (5.1mg, 0.005mmol, 1mol%),Potassium hydroxide (28 mg, 0.5 mmol, 1 equiv), methanol (0.3 mL), and water (0.9 mL) were sequentially added to the reaction vessel. After the reaction mixture was reacted at 130 C for 12 hours in a reaction vessel, it was cooled to room temperature. The solvent was removed by rotary evaporation, and then the purified target compound was obtained by column chromatography (developing solvent: petroleum ether / ethyl acetate), yield: 90%.

Reference： [1]Organic Letters,2017,vol. 19,p. 5790 - 5793
[2]Patent: CN110857278,2020,A .Location in patent: Paragraph 0070-0074
[3]RSC Advances,2012,vol. 2,p. 8645 - 8652
[4]Journal of Organic Chemistry,2020,vol. 85,p. 5815 - 5824

52
[ 703-12-8 ]
[ 637-44-5 ]
N-((4-bromophenyl)sulfonyl)-N-methyl-3-phenylpropiolamide [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 2280 - 2283

53
[ 703-12-8 ]
6-bromo-2-methylphenanthro[9,10-d]isothiazol-3(2H)-one 1,1-dioxide [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 2280 - 2283

54
[ 1119-64-8 ]
[ 703-12-8 ]
N,N'-(3,5-dibutyl-6-methylpyridine-2,4-diyl)bis(4-bromo-N-methylbenzenesulfonamide) [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 9704 - 9708
Angew. Chem.,2016,p. 9856 - 9860,5

55
[ 1119-64-8 ]
[ 703-12-8 ]
4-bromo-N-(hex-1-yn-1-yl)-N-methylbenzenesulfonamide [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 9704 - 9708
Angew. Chem.,2016,p. 9856 - 9860,5

56
methyl N-(4-bromobenzene)sulfonyl-N-methyl-dehydroalaninate [ No CAS ]
[ 703-12-8 ]

Yield	Reaction Conditions	Operation in experiment
74%	With N-Bromosuccinimide; pyridinium polyhydrogenfluoride; In dichloromethane; at 20℃; for 18.5h;	Methyl N-(4-bromobenzene)sulfonyl N-methyl dehydroalaninate (24a) (102 mg, 0.31 mmol) was dissolved in CH2Cl2 (3 mL) and treated with Olah?sreagent (0.18 mL, 0.76 mmol, 2.5 eq.) and NBS (84 mg,0.47 mmol, 1.5 eq.) and the reaction mixture stirred for 18.5 hat r.t. By addition of sat. aq. NaHCO3 the mixture was neutralizedand after phase separation the aqueous phase was extracted with CH2Cl2(10 mL). After that, the combined organic phases were washed with sat. aq.Na2SO3 and sat. aq. NaCl (10 mL each) gewaschen,dried over MgSO4 and the solvent removed under reduced pressure. The only isolated product was N-methyl 4-bromobenzenesulfonamide (28b). Yield: 58 mg (0.23 mmol, 74%).1H NMR (300 MHz, CDCl3): delta 2.60(d, 3JH,H = 5.4 Hz,3 H, 1-CH3), 4.47 (d, 3JH,H = 5.4 Hz, 1 H, NH), 7.50-7.85(m, 4 H, 3/7-CH and 4/6-CH).MS-ES(+)-EM: m/z 271.9365/273.9344 [M+Na]+,calculated for C7H8BrNO2SNa+:271.9352/273.9331.

Reference： [1]Journal of Fluorine Chemistry,2016,vol. 188,p. 65 - 75

57
[ 1158827-44-1 ]
[ 703-12-8 ]

Reference： [1]Journal of Fluorine Chemistry,2016,vol. 188,p. 65 - 75
[2]Journal of Fluorine Chemistry,2016,vol. 188,p. 65 - 75

58
methyl N-(4-bromobenzene)sulfonyl-O-trimethylsilyl-L-serinate [ No CAS ]
[ 703-12-8 ]

Reference： [1]Journal of Fluorine Chemistry,2016,vol. 188,p. 65 - 75
[2]Journal of Fluorine Chemistry,2016,vol. 188,p. 65 - 75

59
methyl N-(4-bromobenzene)sulfonyl-N-methyl-L-serinate [ No CAS ]
[ 703-12-8 ]

Reference： [1]Journal of Fluorine Chemistry,2016,vol. 188,p. 65 - 75

60
C₁₂H₁₆BrNO₇S₂ [ No CAS ]
[ 703-12-8 ]

Reference： [1]Journal of Fluorine Chemistry,2016,vol. 188,p. 65 - 75

61
2-iodo-4,N-dimethyl-N-phenylethynylbenzenesulfonamide [ No CAS ]
[ 703-12-8 ]
C₂₃H₂₁BrN₂O₄S₂ [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2016,vol. 358,p. 1625 - 1638

62
[ 703-12-8 ]
ethyl 3-[4-(methylsulfamoyl)phenyl]-3-oxopropanoate [ No CAS ]

Reference： [1]Patent: WO2017/70081,2017,A1

63
[ 1001-26-9 ]
[ 703-12-8 ]
ethyl-3-ethoxy-3-[4-(methylsulfamoyl)phenyl]prop-2-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With bis[tris( 1,1-dimethylethyl)phosphine]-palladium; N-Methyldicyclohexylamine; lithium chloride; In 1,4-dioxane; for 16h;Inert atmosphere; Reflux;	A flask containing lithium chloride (50.9 mg, 1.2 mmol), 4-bromo-N-methylbenzene-1- sulfonamide (100 mg, 0.4 mmol), N-cyclohexyl-N-methylcyclohexanamine (93.38 .il, 0.44 mmol),ethyl-3-ethoxyprop-2-enoate (172.92 mg, 1.2 mmol) in 1,4-dioxane (2 mL) was degassed by passing a stream of nitrogen through the mixture for 10 minutes. palladium - tri-tert-butylphosphane (12.26 mg, 0.02 mmol) was added, and reaction mixture was heated at reflux under nitrogen for 16 hours. The brown mixture was cooled and partitioned between ethyl acetate (10 mL) and water (3 mL). The layers were separated, and the organic layer was washed sequentially with saturated ammonium chloridesolution (5 mL) and brine (5 mL), followed by drying over sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to give an oil which was purified by silica gel chromatography eluting with 10?50percent ethyl acetate in heptane to afford the desired compound as an orange oil (54 mg, 43percent yield). LC-MS tR = 1.1 mi [M+Hj = 314, ?H NMR (500 MI-Tz, DMSO-d6) 7.89 - 7.79 (m, 4H), 7.76 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 5.84 (s, 1H), 4.12 (q, J = 7.1 Hz,2H), 4.03 (q, J = 7.0 Hz, 2H), 2.43 (s, 3H), 1.30 (t, J = 7.0 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H).

Reference： [1]Patent: WO2017/70081,2017,A1 .Location in patent: Page/Page column 190; 191

64
[ 703-12-8 ]
[ 4105-21-9 ]
4-bromo-N-methyl-N-(2-phenylimidazo[1,2-a]pyridin-3-yl)benzenesulfonamide [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 8102 - 8109

65
[ 703-12-8 ]
4-(2-(1-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4-b]pyridin-5-yl)-N-methylbenzenesulfonamide [ No CAS ]

Reference： [1]Patent: US2017/291910,2017,A1

66
[ 703-12-8 ]
N-methyl-3'-(2-methylpropanoyl)-N-(2,2,2-trifluoroethyl)-5'-(trifluoromethyl)-1,1’-biphenyl-4-sulfonamide [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 14345 - 14357

67
[ 703-12-8 ]
3'-(1,1-dicyano-3-methylbut-1-en-2-yl)-N-methyl-N-(2,2,2-trifluoroethyl)-5'-(trifluoromethyl)-1,1’-biphenyl-4-sulfonamide [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 14345 - 14357

68
[ 703-12-8 ]
(±)-3'-[6-amino-5-cyano-3-methyl-4-isopropyl-2,4-dihydropyrano[2,3-c]pyrazol-4-yl]-N-methyl-N-(2,2,2-trifluoroethyl)-5'-(trifluoromethyl)(1,1’-biphenyl)-4-sulfonamide [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 14345 - 14357

69
[ 6226-25-1 ]
[ 703-12-8 ]
4-bromo-N-methyl-N-(2,2,2-trifluoroethyl)benzenesulfonamide [ No CAS ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 14345 - 14357

70
[ 106-53-6 ]
[ 703-12-8 ]

Reference： [1]Patent: US2017/291910,2017,A1

71
lithium 6-methoxypyridine-3-sulfinate [ No CAS ]
[ 703-12-8 ]
4-(6-methoxypyridin-3-yl)-N-methylbenzenesulfonamide [ No CAS ]

Reference： [1]Organic Letters,2017,vol. 19,p. 6033 - 6035

72
[ 703-12-8 ]
[ 932-87-6 ]
4-bromo-N-methyl-N-(2-methyl-5-phenyloxazol-4-yl)benzenesulfonamide [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 10583 - 10594

73
[ 703-12-8 ]
[ 932-87-6 ]
[ 1268824-72-1 ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 10583 - 10594
[2]Chemistry - An Asian Journal,2019,vol. 14,p. 4828 - 4836

74
[ 703-12-8 ]
[ 93-55-0 ]
(E)-4-bromo-N-methyl-N-(3-oxo-3-phenylprop-1-en-1-yl)benzenesulfonamide [ No CAS ]

Reference： [1]Chemical Communications,2018,vol. 54,p. 8403 - 8406

75
[ 110-82-7 ]
[ 703-12-8 ]
4-bromo-N-(cyclohexylmethyl)benzenesulfonamide [ No CAS ]

Reference： [1]Organic Letters,2018,vol. 20,p. 6420 - 6424

76
[ 111-55-7 ]
[ 703-12-8 ]
C₁₁H₁₄BrNO₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With hafnium(IV) trifluoromethanesulfonate; at 120℃; for 14h;Sealed tube;	146 mg of ethylene glycol diacetate 1a, 125 mg of nitrogen methyl p-bromobenzenesulfonamide 2d, were sequentially added to a 5 mL sample vial.7.1 mg of ytterbium triflate. The seal is heated to 120 C, stirred for 14 hours, nitrogen methyl p-bromobenzenesulfonamide 2d to ethylene glycol diThe ester group of the acid ester 1a is substituted and separated by column chromatography (petroleum ether: ethyl acetate = 4:1) to obtain the product 3ad, which is derived from the amino alcohol.The amino group is derivatized as a sulfonamide group and retains at least one carboxylate group. The isolated yield was 93%.

Reference： [1]Patent: CN108707096,2018,A .Location in patent: Paragraph 0142; 0143; 0144

77
[ 18617-50-0 ]
[ 703-12-8 ]
C₁₅H₁₆N₂O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43.1%	With copper(l) iodide; caesium carbonate; rac-Pro-OH; In dimethyl sulfoxide; at 10℃; for 6h;	Compound 1a (19.0 g, 100.0 mmol),Compound 1b (16.7 g, 100.0 mmol),caesium carbonate (65.2 g, 200.0 mmol), cuprous iodide (9.5 g, 50.0 mmol),Proline (1.2 g, 10.0 mmol) was dissolved in DMSO (200 ml).The reaction was stirred at 10 C for 6 hours, and the reaction was detected by TLC.After the reaction was completed, water (200 ml) and ethyl acetate (500 ml) were added.The organic layer is dried, filtered and concentrated.Column chromatography gave 14.5 g of a white solid.The yield was 43.1%.

Reference： [1]Patent: CN108794393,2018,A .Location in patent: Paragraph 0098; 0100; 0101; 0102

78
[ 703-12-8 ]
C₁₃H₁₂N₂O₅S [ No CAS ]

Reference： [1]Patent: CN108794393,2018,A

79
[ 703-12-8 ]
N-(3-bromo-4-fluorophenyl)-1-(4-(N-methylaminosulfonyl)phenyl)-6-oxo-1,6-dihydropyridine-3-carboxamide [ No CAS ]

Reference： [1]Patent: CN108794393,2018,A

80
[ 703-12-8 ]
N-(3-bromo-4-fluorobenzene)-5-cyclopropyl-1-(4-(N-methylaminosulfonyl)phenyl)-6-oxo-1,6-dihydropyridine- 3-carboxamide [ No CAS ]

Reference： [1]Patent: CN108794393,2018,A

81
[ 703-12-8 ]
C₁₉H₁₄Br₂FN₃O₄S [ No CAS ]

Reference： [1]Patent: CN108794393,2018,A

82
[ 703-12-8 ]
C₁₂H₁₁BrO [ No CAS ]
N-((2-((allyloxy)methyl)phenyl)ethynyl)-4-bromo-N-methylbenzenesulfonamide [ No CAS ]

Reference： [1]Green Chemistry,2019,vol. 21,p. 3023 - 3028

83
[ 703-12-8 ]
[ 1066-54-2 ]
N‐methyl‐4‐[(trimethylsilyl)ethynyl]benzenesulfonamide [ No CAS ]