Name: 94108-56-2|4-(Trifluoromethoxy)benzenesulfonyl chloride|98%
Brand: Ambeed
SKU: A442456
Price: 8.0 USD
Availability: InStock
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1
[ 94108-56-2 ]
[ 685542-10-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate; In dichloromethane; at 20℃;	General procedure: 0.01 mol 4-substituted phenylsulfonyl chloride was addedinto 0.04 mol hydrazine monohydrate in dichloromethanedropwise, stirred at room temperature and monitored byTLC after dichloromethane was distilled off and the crudeproduct was washed with water and hexane (Siemannet al., 2002; Kummerle et al., 2012).
	With hydrazine hydrate; In tetrahydrofuran; at 0℃; for 0.5h;Inert atmosphere;	General procedure: Hydrazine hydrate (12.5 mmol) was added dropwise to a solution of sulfonyl chloride(5.0 mmol) in dry THF (25 mL) at 0C under N2. After vigorous stirring for 30 min at0C, ethyl acetate (60 mL) was added, and the mixture was washed repeatedly withice-cold 10% aqueous sodium chloride solution (3 × 20 mL). The organic layer wasdried over sodium sulfate, filtered, and added slowly to stirred hexane (40 mL) over 5min. Sulfonyl hydrazide precipitated within 10 min as an off-white solid and wascollected by vacuum filtration. The filter cake was washed with hexanes (2 × 50 mL)and then was dried in vacuum to give corresponding sulfonyl hydrazides in 60-80%yields.
	With hydrazine hydrate; In tetrahydrofuran; water; at 0℃; for 0.5h;	General procedure: Hydrazine monohydrate (80%) (275 mg, 4.4 mmol) was added water (260 mg) and was cooled to 0 C. To this solution was added dropwise a solution of arylsulfonyl chloride (2.0 mmol) in THF (10 mL) at 0 C. The mixture was further stirred at 0 C for 30 min., followed by addition of diethyl ether (10 mL). The mixture was extracted with saturated brine (3 × 10 mL). The organic layer was dried over sodium sulfate, filtered through Celite. The combined organic extracts were concentrated and the resulting residue was purified by column chromatography on silica gel to provide the desired product.

Reference： [1]Antimicrobial Agents and Chemotherapy,2002,vol. 46,p. 2450 - 2457
[2]Green Chemistry,2014,vol. 16,p. 4106 - 4109
[3]Medicinal Chemistry Research,2016,vol. 25,p. 1590 - 1607
[4]Organic Letters,2018,vol. 20,p. 4023 - 4027
[5]Molecules,2020,vol. 25
[6]Journal of Molecular Structure,2020,vol. 1211
[7]Tetrahedron Letters,2020

2
[ 94108-56-2 ]
[ 160232-08-6 ]
[ 160232-85-9 ]

Yield	Reaction Conditions	Operation in experiment
89.7%	With dmap; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0 - 20℃;	To an ice-cooled solution of the secondary amine 6 (5.00g, 14.9mmol) in anhydrous THF (40mL) was added 3.68mL (2.11g, 16.3mmol) of DIEA and DMAP (0.18g, 1.49mmol) followed by the addition of <strong>[94108-56-2]4-(trifluoromethoxy)benzenesulfonyl chloride</strong> (4.25g, 16.3mmol) solution in anhydrous THF (15mL) slowly. After stirring 0.5h at 0C, the reaction mixture was warmed to room temperature and stirred 3-5h. The solvents were removed under diminished pressure and the residue was added water (30mL) and extracted with three 40mL portions of ethyl acetate. The combined organic extracts were dried over Na2SO4 and concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (20×4cm). Elution with 5:1 hexanes-ethyl acetate gave 11 as a colorless solid: yield 7.49g (89.7%), mp 136-138C. 1H NMR (400MHz, CDCl3) delta 7.85-7.81 (m, 2H), 7.33 (d, J=8.4Hz, 2H), 7.30-7.28 (m, 2H), 7.25-7.21 (m, 3H), 4.63 (d, J=6.8Hz, 1H), 3.82-3.76 (m, 2H), 3.13-3.11 (m, 2H), 3.03-2.86 (m, 4H), 1.92-1.82 (m, 1H), 1.35 (s, 9H), 0.90 (d, J=6.4Hz, 3H), 0.87 (d, J=6.4Hz, 3H); LC-MS (ESI) [M+H]+ m/z 561.0.

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 137,p. 30 - 44
[2]Journal of Medicinal Chemistry,2006,vol. 49,p. 7342 - 7356

3
[ 41979-39-9 ]
[ 94108-56-2 ]
[ 1002750-63-1 ]

Yield	Reaction Conditions	Operation in experiment
93%		A suspension of 4-piperidone monohydrate hydrochloride (5.0 g, 33 mmol) and diisopropylethylamine (17 ml, 98 mmol) in DMF (200 ml) was stirred at 80 "C for 30 minutes and the resulted solution was cooled at 0 C. To this ice-cooled solution, a solution of 4-trifluoromethoxysulfonyl chloride (11.0 g, 39 mmol) in DMF (40 ml) was added dropwise and the whole was stirred at room temperature overnight. The solvent was evaporated under reduced pressure and ice-water (80 ml) was added to the residue. The precipitated material was collected, washed with water (50 ml x 3) and n-hexane (30 ml) and dried under reduced pressure at 80 0C to give l-(4- (trifluoromethoxy)phenylsulfonyl)piperidin-4-one (9.8 g, 93 %).
81%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃;	4-Trifluoromethoxyphenylsulfonyl chloride (4.34 g, 16.7 mmol) was added to a solution of 4-piperidone monohydrate hydrochloride (2.99 g, 19.5 mmol) and N5N- diisopropylethylamine (9.50 ml, 57.5 mmol) in CH2Cl2 (50 ml) at 00C and stirred at room temperature for 20hours. The reaction mixture was concentrated in vacuo and the residue was diluted with ethyl acetate (250 ml), washed with aqueous 1 N HCl solution (50 ml), H2O (50 ml), saturated aqueous NaHCO3 solution (50 ml) and brine (50 ml), dried over Na2SO4 and concentrated in vacuo to give l-(4-(trifluoromethoxy)phenylsulfonyl)piperidin-4-one (4.37 g, 81 %) as a off-white solid.
79%	With N-ethyl-N,N-diisopropylamine; In water; N,N-dimethyl-formamide; at 0 - 20℃; for 72.5h;	Examples} EXAMPLE 1N-(cyclopropylmethyl)-2-(l-(4-(trifluoromethoxy)phenylsulfonyl)piperidin-4- ylidene)acetamidea) 4-(Trifluoromethoxy)benzenesulfonyl chloride (15.O g, 56.4 mmol) was added over 30 minutes at 0 "C to a solution of 4-piperidone monohydrate hydrochloride (7.22 g,47.0 mmol) and N,N-diisopropylethylamine (DIPEA, 17.7 ml, 103 mmol) in N,N- dimethylformamide (DMF, 200 ml). The reaction mixture was stirred at room temperature for 3 days. The reaction mixture was quenched with H2O (800 ml) and the resulting precipitation was collected and washed with H2O and n-hexane to give l-(4- (trifluorornethoxy)phenylsulfonyl)piperidin-4-one (11.9 g, 79 %) as a pale-yellow solid.

76%	With triethylamine; In dichloromethane; water; at 0 - 20℃; for 4h;	4-(Trifluoromethoxy)benzenesulfonyl chloride (5.0 g, 19 mmol) was added to a solution of 4-piperidone monohydrate hydrochloride (3.0 g, 17 mmol) and triethylamine <n="159"/>(6 ml, 82 mmol) in CH2Cl2 (40 ml) at O C. The reaction mixture was warmed to room temperature and stirred for 4 hours, washed with water (20 ml) and brine (15 ml), and concentrated under reduced pressure. The residue was purified by column chromatography on silica (EtOAc/Hexanes 30/70) to give l-(4-(trifluoromethoxy)phenylsulfonyl)piperidin-4- one as a white solid (4.5 g, 76 %, colorless solid).
53%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 80℃; for 1h;	4-(Trifiuoromethoxy)benzenesulfonyl chloride (4.95 g, 18.6 mmol) was added to a solution of 4-piperidone monohydrate hydrochloride (2.92 g, 18.6 mmol) and N,N- diisopropylethylamine (9.60 ml, 55.8 mmol) in N,N-dimethylformamide (60 ml) at 0 C and stirred at room temperature for 30 minutes and at 80 C for 30 minutes. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (150 ml), washed with H2O (50 ml) and brine, dried (MgSO4) and evaporated under reduced <n="439"/>pressure. The residue was purified by column chromatography on silica (ethyl acetate/hexane 30/70-50/50) to give l-(4-(trifluoromethoxy)phenylsulfonyl)piperidin- 4-one as a white solid (3.38 g, 53 %, colorless solid).
46.6%	With pyridine; at 20℃; for 3h;	Compound 3-14To a solution of compound 3-1 (100 mg, 0.7375 mmol) in pyridine (3 mL) was added 4-trifluoromethoxybenzene-1-sulfonyl chloride (192.38 mg, 0.7375 mmol) and the reaction mixture was stirred at room temperature for 3 hours. Water was added and the resulting reaction mixture was extracted with CH2Cl2 3 times. The combined organic layers were washed with 3M HCl and concentrated to give compound 3-14 (111 mg, yield: 46.6%, NMR confirmed) as a white solid.

Reference： [1]Patent: WO2008/150470,2008,A1 .Location in patent: Page/Page column 82-83
[2]Patent: WO2009/151152,2009,A1 .Location in patent: Page/Page column 60
[3]Patent: WO2010/114181,2010,A1 .Location in patent: Page/Page column 73
[4]Patent: WO2008/150447,2008,A1 .Location in patent: Page/Page column 157-158
[5]Patent: WO2008/8398,2008,A2 .Location in patent: Page/Page column 437-438
[6]Patent: US2010/280057,2010,A1 .Location in patent: Page/Page column 23

4
[ 726185-68-8 ]
[ 94108-56-2 ]
2-[4-(4-trifluoromethoxy-benzene sulfonyl)-piperazin-1-yl]-thiazole-5-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78.8%	With triethylamine; In dichloromethane; at 20℃; for 4h;	To a solution of compound 11 (200 mg, 0.886 mmol) in dichloromethane (7.5 mL) were added 4-trifluoromethoxybenzenesulfonyl chloride (344 mg, 1.320 mmol) and triethylamine (220 mg, 2.169 mmol) under a N2 atmosphere. The reaction mixture was stirred at room temperature for 4 h. Water (10 mL) followed by dichloromethane (10 mL) were added to the reaction mixture and the organic layer was separated, dried on sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using silica gel to give the compound 12d as a solid (313 mg, 78.8%). HPLC: 98% (Rt=12.22 min). 1H NMR (CDCl3, 200 MHz) delta: 7.82 (3H, m), 7.44 (2H, d, J=8.0 Hz), 3.84 (3H, s), 3.74 (4H, t, J=5.8 Hz), 3.20 (4H, t, J=5.8 Hz). MS (m/z): 451 (M+1).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5995 - 5999
[2]Patent: US2005/234033,2005,A1 .Location in patent: Page/Page column 36

5
[ 103529-16-4 ]
[ 94108-56-2 ]
[ 668971-41-3 ]

Yield	Reaction Conditions	Operation in experiment
76%	With pyridine; In dichloromethane; at 20℃;	[2- [ (TRIMETHYLSILYL)] ethynyl] aniline (2000 mg, 10.6 mmol) and 4- (trifluoromethoxy) [BENZENESULFONYL] chloride (2500 mg, 9.6 mmol) were dissolved in DCM (10 ml). Pyridine (0.4 [ML)] was added. And the n the solution was stirred at room temperature over night. The resulting solution was stirred overnight, then diluted with MTBE [(200 ML)] and washed with IN HCl, IN [NAOH,] brine, dried [(MGS04),] filtered, and concentrated in vacuo. The residue was recrystallized from MeOH to afford 3340 mg (76%) [OF 4- (TRIFLUOROMETHOXY)-N- {2-] [(trimethylsilyl) ethynyl] phenyl} benzenesulfonamide as a white solid

Reference： [1]Patent: WO2004/18428,2004,A1 .Location in patent: Page 307

6
[ 94108-56-2 ]
[ 57260-71-6 ]
[ 847039-26-3 ]

Yield	Reaction Conditions	Operation in experiment
72%	With triethylamine; In dichloromethane;	Compound IV-5 (7.45 g, 40 mmol) was dissolved in dichloromethane (100 mL).Compound IV-6 (7.465 mL, 44 mmol) and triethylamine (11.119 mL, 80 mmol) were added, and the reaction was stirred overnight.The reaction was monitored by TLC for completion.Dichloromethane (50 mL) was added to dilute the reaction solution.The organic phase was washed with water (50 mL x 2) and saturated brine (30 mL x 2),Dry over anhydrous sodium sulfate.After filtration and concentration,The solvent was distilled off under reduced pressure,The residue was recrystallized from ethanol to obtain compound IV-7 (white solid, 11.939 g, yield 72%).
		To a solution of PIPERAZINE-1-CARBOXYLIC acid tert-butyl ester (521 mg, 2.8 MMOL) in DCM (6 ml) was added NEt3 (547 mul, 3.92 mmol, 1.4 eq. ) and 4- trifluoromethoxy-benzenesulfonyl chloride (880 mg, 3.36 MMOL, 1.2 eq. ). The reaction mixture was stirred at room temperature for 12 hrs. The excess of sulfonyl chloride was quenched by addition of trisamine resin (150 mg), and subsequent stirring for 2 hrs. The resin was then filtered off, and NAHCO3 sat (5 ml) was added. Filtration of the resulting mixture through hydrophobic catridge and subsequent removal of the solvent under reduced pressure afforded the desired 4- (4-TRIFLUOROMETHOXY-BENZENESULFONYL)-PIPERAZINE-1- carboxylic acid tert-butyl ester in quantitative yield.
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 1.5h;	Description 111-({4-[(trifluoromethyl)oxy]phenyl}sulfonyl)piperazine To a solution of 1,1-dimethylethyl 1-piperazinecarboxylate (5 g, 26.8 mmol) in DCM (200 ml) was added DIPEA (9.85 ml, 56.4 mmol) and then <strong>[94108-56-2]4-[(trifluoromethyl)oxy]benzenesulfonyl chloride</strong> (4.55 ml, 26.8 mmol). The reaction mixture was stirred for 1.5 hours at rt. The reaction mixture was then evaporated to dryness in vacuo. The residue was then dissolved in 1,4-dioxane (100 ml) and 4M HCl in 1,4-dioxane (50 ml) was added, along with a few drops of distilled water. The reaction mixture was stirred for 3 hrs. Then the reaction mixture was evaporated to dryness in vacuo. The residue was dissolved in DCM (200 ml) and washed with 2M aq. NaOH (50 ml, twice). The organic layer was dried over anhydrous magnesium sulphate, the solid removed by filtration, and filtrate evaporated to dryness in vacuo. The residue was not a solid so was dissolved in ether and evaporated in vacuo to remove any remaining solvent. The title compound (8.02 g) was obtained as a pale yellow solid.m/z (API-ES) 311 [M+H]+ 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 2.92-2.98 (m, 4H), 2.98-3.04 (m, 4H), 3.60-3.80 (m, 1H), 7.37 (d, J=8.9 Hz, 2H), 7.73-7.88 (d, J=8.9 Hz, 2H).

	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0℃;Inert atmosphere;	Intermediate 10: 1 ,1 -Dimethylethyl 4-({4-[(trifluoromethyl)oxy]phenyl}sulfonyl)- 1 -piperazinecarboxylateTo a solution of 1 ,1 -dimethylethyl 1 -piperazinecarboxylate (5 g, 19.19 mmol, supplier Aldrich), in DCM (80 ml_), DIPEA (5.03 ml_, 28.8 mmol) was added under argon atmosphere at room temperature then <strong>[94108-56-2]4-[(trifluoromethyl)oxy]benzenesulfonyl chloride</strong> (2.326 ml_, 19.19 mmol) was added at 0C then ice bath was removed and the reaction mixture was stirred for 3 hrs. The reaction mixture was partitioned between DCM (30ml) and sodium bicarbonate (2X20ml). The organic phase was washed with HCI (2X20ml) and water (2X20ml), then it was dried using phase separator and DCM was removed under vacuum to give the title compound (5.5 g) as a yellow viscous liquid.LCMS (high pH) RT 1 .28min, m/z (ES) 31 1 [M-Boc+H]+
5.5 g	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 3h;Inert atmosphere;	Intermediate 10: 1,1-Dimethylethyl 4-({4-[(trifluoromethyl)oxy]phenyl}sulfonyl)-1-piperazinecarboxylate [0199][0200]To a solution of 1,1-dimethylethyl 1-piperazinecarboxylate (5 g, 19.19 mmol, supplier Aldrich), in DCM (80 mL), DIPEA (5.03 mL, 28.8 mmol) was added under argon atmosphere at room temperature then <strong>[94108-56-2]4-[(trifluoromethyl)oxy]benzenesulfonyl chloride</strong> (2.326 mL, 19.19 mmol) was added at 0 C. then ice bath was removed and the reaction mixture was stirred for 3 hrs. The reaction mixture was partitioned between DCM (30 ml) and sodium bicarbonate (2×20 ml). The organic phase was washed with HCl (2×20 ml) and water (2×20 ml), then it was dried using phase separator and DCM was removed under vacuum to give the title compound (5.5 g) as a yellow viscous liquid.[0201]LCMS (high pH) RT 1.28 min, m/z (ES) 311 [M-Boc+H]+

Reference： [1]Patent: CN110372638,2019,A .Location in patent: Paragraph 0161; 0163; 0166
[2]Patent: WO2005/19194,2005,A1 .Location in patent: Page/Page column 51
[3]Patent: US2010/16330,2010,A1 .Location in patent: Page/Page column 10-11
[4]Patent: WO2011/86377,2011,A1 .Location in patent: Page/Page column 29
[5]Patent: US2013/72499,2013,A1 .Location in patent: Paragraph 0198-0201

7
[ 99-92-3 ]
[ 94108-56-2 ]
[ 782483-67-4 ]

Yield	Reaction Conditions	Operation in experiment
89%		Step 1: N-[4-(2-Bromoacetyl)-phenyl]-4-trifluoromethoxybenzenesulfonamide 4-Trifluoromethoxybenzenesulfonyl chloride (3.18 g, 2.07 mL, 1.22 mmol) was added to a solution of 4'-aminoacetophenone (1.5 g, 1.11 mmol) and triethylamine (3.1 mL, 2.22 mmol) in anhydrous methylene chloride (50 mL). The reaction was stirred for 16 hours and then poured into water (50 mL), and extracted with diethyl ether (330 mL). The combined extract was washed with 0.5 N hydrochloric acid (210 mL), water and finally brine. The ethereal solution was dried over anhydrous MgSO4, filtered and concentrated in vacuo. The product methyl ketone was used in the subsequent bromination step without further purification. Phenyltrimethylammonium tribromide (4.68 g, 1.22 mmol) was added to a solution of the methyl ketone (prepared in the previous step) in anhydrous dioxan (50 mL). The reaction eas stirred at room temperature for 3 hours and then poured into water (50 mL), and extracted with diethyl ether (3*30 mL). The combined extract was washed with 0water and brine. The ethereal solution was dried over anhydrous MgSO4, filtered and concentrated in vacuo. Purification of the product by flash column chromatography, using 20% ethyl acetate/heptane as eluent, afforded the title compound has a white solid (4.36 g, 89%);

Reference： [1]Patent: US2006/100251,2006,A1 .Location in patent: Page/Page column 22

8
[ 94108-56-2 ]
[ 7440-66-6 ]
[ 169685-29-4 ]

Yield	Reaction Conditions	Operation in experiment
47%	With sodium bicarbonate In sulfuric acid; water; ethyl acetate	13 Preparation of 2-amino-9-[2-[bis(2,2,2-trifluoroethyl)-phosphonylmethoxy]ethyl]-6-p-trifluoromethoxyphenylthiopurine (Compound No. 35) Example 13 Preparation of 2-amino-9-[2-[bis(2,2,2-trifluoroethyl)-phosphonylmethoxy]ethyl]-6-p-trifluoromethoxyphenylthiopurine (Compound No. 35) Zinc powder (3.1 g) was added to a suspension of p-trifluoromethoxybenzenesulfonyl chloride (1.36 ml) in concentrated sulfuric acid (3.4 ml) and water (20 ml), and the suspension was stirred at 0° C. for 18 hours and heated under reflux for 6 hours. The mixture was added with ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate, and saturated brine, and then concentrated under reduced pressure to give p-trifluoromethoxybenzenethiol (0.73 g, 47%).

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION; Mitsubishi Chemical Corp (in: MCHC Group) - US5840716, 1998, A

9
[ 883901-92-6 ]
[ 94108-56-2 ]
[ 883901-50-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With triethylamine; In tetrahydrofuran; at 10 - 20℃; for 16h;	To a solution of 3-(3-amino-phenyl)-pyrrolidine-1-carboxylic acid methyl ester (500 mg, 2.27 mmol) and triethylamine (500 mg, 4.94 mmol) in THF (20 ml) at 100C 4- trifluoromethoxy-benzenesulfonylchloride (600 mg, 2.3 mmol) was added. The mixture was allowed to come to room temperature and was stirred for 16 h. The mixture was ? poured into water and extracted three times with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution, dried over MgSO4 and evaporated under reduced pressure to give the product as a brown oil (1 g, 99%).

Reference： [1]Patent: WO2006/40182,2006,A1 .Location in patent: Page/Page column 129

10
[ 883993-09-7 ]
[ 94108-56-2 ]
[ 883993-10-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine; In tetrahydrofuran; at -5 - 20℃; for 2h;	To a solution of N-[(S)-2-(4-amino-phenyl)-1-methyl-ethyl]-propionamide (300 mg, 1.45 mmol) and triethylamine (300 mg, 2.96 mmol) in tetrahydrofuran (THF) (30 ml) 4- trifluoromethoxy-benzenesulfonyl chloride (380 mg, 1.45 mmol) was added at -5-00C. The mixture was stirred at room temperature for 2 h. The mixture was partitioned be- tween water and ethyl acetate. The organic layer was washed with 5% citric acid, satu¬ rated aqueous NaHCO3, water, and brine, dried over MgSO4 and the solvent evapo¬ rated under reduced pressure to give the product as a brown oil (500 mg, 80%).

Reference： [1]Patent: WO2006/40179,2006,A1 .Location in patent: Page/Page column 109

11
[ 161958-61-8 ]
[ 94108-56-2 ]
[ 881675-10-1 ]

Yield	Reaction Conditions	Operation in experiment
94%		Reference Example 151 Ethyl 5-phenyl-1-[4-(trifluoromethoxy)phenyl]sulfonyl}-1H-pyrrole-3-carboxylate Sodium hydride (60% in oil, 0.20 g) was added to a solution (20 mL) of ethyl 5-phenyl-1H-pyrrole-3-carboxylate (0.71 g) in tetrahydrofuran under ice-cooling. After stirring at the same temperature for 15 min, <strong>[94108-56-2][4-(trifluoromethoxy)benzene]sulfonyl chloride</strong> (1.00 g) was added, and the mixture was stirred at room temperature for 4 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:2) to give the title compound as an oil (yield 1.36 g, 94%). 1H-NMR (CDCl3)delta: 1.36 (3H, t, J=7.1 Hz), 4.32 (2H, q, J=7.1 Hz), 6.56 (1H, s), 7.13 (4H, dd, J=13.0 Hz), 7.28-7.42 (5H, m), 8.08 (1H, d, J=1.9 Hz).
	In tetrahydrofuran; water;	Reference Example 151 Ethyl 5-phenyl-1-[4-(trifluoromethoxy)phenyl]sulfonyl}-1H-pyrrole-3-carboxylate Sodium hydride (60% in oil, 0.20 g) was added to a solution (20 mL) of ethyl 5-phenyl-1H-pyrrole-3-carboxylate (0.71 g) in tetrahydrofuran under ice-cooling. After stirring at the same temperature for 15 min, <strong>[94108-56-2][4-(trifluoromethoxy)benzene]sulfonyl chloride</strong> (1.00 g) was added, and the mixture was stirred at room temperature for 4 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:2) to give the title compound as an oil (yield 1.36 g, 94%). 1H-NMR (CDCl3)delta: 1.36 (3H, t, J=7.1 Hz), 4.32 (2H, q, J=7.1 Hz), 6.56 (1H, s), 7.13 (4H, dd, J=13.0 Hz), 7.28-7.42 (5H, m), 8.08 (1H, d, J=1.9 Hz).

Reference： [1]Patent: WO2006/36024,2006,A1 .Location in patent: Page/Page column 169-170; 289
[2]Patent: EP2336107,2015,B1 .Location in patent: Paragraph 0325
[3]Patent: EP1803709,2007,A1

12
[ 24629-25-2 ]
[ 94108-56-2 ]
[ 1054529-22-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4232 - 4236

13
[ 1240315-26-7 ]
[ 94108-56-2 ]
[ 1240315-17-6 ]

Yield	Reaction Conditions	Operation in experiment
79%	With triethylamine; In dichloromethane; at 20℃; for 18h;Cooling with ice; Inert atmosphere;	Example 12 1-[(3R)-1-({4-[(trifluoromethyl)oxy]phenyl}sulfonyl)-3-piperidinyl]-2-pyrrolidinone (E12) A solution of 1-[(3R)-3-piperidinyl]-2-pyrrolidinone hydrochloride (D5) (500 mg, 2.44 mmol) and triethylamine (0.749 ml, 5.37 mmol) in dichloromethane (DCM) (10 ml) was cooled in an ice-water bath under argon before the addition of 4- [(trifluoromethyl)oxy]benzenesulfonyl chloride (0.414 ml, 2.443 mmol). The reaction was allowed to warm to room temperature and stirred for 18 hours. The reaction was diluted with DCM (3OmL) and water (2OmL). The aqueous layer was separated and extracted with DCM (2OmL). The DCM layers were combined, passed through a hydrophobic frit and evaporated to dryness in vacuo. The residue was purified by silica chromatography (Biotage SP4, eluting 70% ethyl acetate in iso-hexanes (3 column volumes), a gradient form 70-100% ethyl acetate (over 9 column volumes) then ethyl acetate (3 column volumes)) to yield the title compound as a white solid (0.755g, 79%).1H NMR (400 MHz, Choloroform -D) delta ppm 1.6 (m, 2 H) 1.8 (m, 2 H) 2.0 (m, 2 H) 2.4 (m, 2 H) 2.5 (m, 1 H) 2.6 (dd, J=11.0, 10.3 Hz, 1 H) 3.4 (m, 2 H) 3.6 (m, 2 H) 4.0 (m, 1 H) 7.4 (d, J=9.6 Hz, 2 H) 7.8 (m, 2 H)MS ES+ve m/z 393 (M+H)

Reference： [1]Patent: WO2010/91721,2010,A1 .Location in patent: Page/Page column 31-32

14
[ 1209874-15-6 ]
[ 94108-56-2 ]
[ 1240315-21-2 ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine; In dichloromethane; at 20℃; for 18h;	Example 16 1-[1-({4-[(Trifluoromethyl)oxy]phenyl}sulfonyl)-3-piperidinyl]-2-imidazolidinone(E16) To a solution of 1-(3-piperidinyl)-2-imidazolidinone (D14) (0.112 g, 0.662 mmol) and triethylamine (0.11 1 ml, 0.794 mmol) in dichloromethane (DCM) (3ml) was added 4- [(trifluoromethyl)oxy]benzenesulfonyl chloride (0.1 18 ml, 0.695 mmol). The reaction was shaken at room temperature for 18 hours. The reaction was diluted with DCM (2ml) and water (2ml_) added. The reaction was vigorously shaken then the organic layer collected via a hydrophobic frit and the solvent evaporated under a stream of argon.The residue was purified by silica chromatography (Biotage SP4, eluting with 70% EtOAc in iso-hexane (3 column volumes) then a gradient from 70-100% (over 10 column volumes) then EtOAc (5 column volumes)) to yield the title compound as a white solid (208mg, 80%).1H NMR (400 MHz, Chloroform-D) delta ppm 1.6 (m, 2 H) 1.8 (m, 2 H) 2.5 (td, J=11.2, 2.7 Hz, 1 H) 2.6 (dd, J=11.0, 10.1 Hz, 1 H) 3.4 (m, 3 H) 3.5 (m, 1 H) 3.6 (m, 1 H) 3.7 (m, 1 H) 3.8 (m, 1 H) 4.4 (s, 1 H) 7.4 (m, 2 H) 7.8 (m, 2 H)MS ES+ve m/z 394 (M+H)

Reference： [1]Patent: WO2010/91721,2010,A1 .Location in patent: Page/Page column 34-35

15
[ 6457-49-4 ]
[ 94108-56-2 ]
[ 1246449-06-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With potassium carbonate; In 1,4-dioxane; water; at 0 - 20℃;	EXAMPLE 36(Z)-N-cyclopropy 1-3 -methoxy-3 -( 1 -(4-(trifluoromethoxy)phenylsulfonyl)piperidin-4- yl)acrylamide a) A solution of <strong>[94108-56-2]4-(trifluoromethoxy)benzenesulfonyl chloride</strong> (9.05 g, 34.7 mmol) in 1,4-dioxane (40 ml) was added dropwise at 0 C to a solution of piperidin-4- ylmethanol (4.00 g, 34.7 mmol) and K2CO3 (7.20 g, 52.1 mmol) in H2O (40 ml), and the whole was stirred at room temperature for 1 hour. After the reaction mixture was diluted with H2O, the whole was extracted with ethyl acetate (200 x 2 ml). The combined organic phase was washed with 1 N HCl solution, H2O, saturated NaHCO3 solution, H2O and brine, dried over MgSO4, filtered and concentrated in vacuo. The residual solid was triturated with diethyl ether and n-hexane to give (l-(4- (trifluoromethoxy)phenylsulfonyl)piperidin-4-yl)methanol (1 1.0 g, 93 %) as a white solid.

Reference： [1]Patent: WO2010/114181,2010,A1 .Location in patent: Page/Page column 97; 98

16
[ 103003-01-6 ]
[ 94108-56-2 ]
[ 1246449-28-4 ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium carbonate; In 1,4-dioxane; water; at 0 - 20℃;	EXAMPLE 44(Z)-N-cyclopropyl-2-methoxy-3-(4-(4-(trifluoromethoxy)phenylsulfonyl)morpholin-2- yl)acrylamidea) A solution of 4-(trifluoromethoxy)benzenesulfonyl chloride (3.69 g, 14.2 mmol) in 1,4-dioxane (20 ml) was added dropwise at 0 C to a solution of morpholin-2- ylmethanol (1.66 g, 14.2 mmol) and K2CO3 (3.50 g, 25.3 mmol) in H2O (20 ml), and the whole was stirred at room temperature for 24 hours. After the reaction mixture was diluted with H2O, the aqueous phase was extracted with ethyl acetate (200 ml x 2). The combined organic phase was washed with H2O and brine, dried over MgSO4, filtered and concentrated in vacuo. The residual solid was recrystallized from ethyl acetate/n-hexane to give (4-(4-(trifluoromethoxy)phenylsulfonyl)morpholin-2- yl)methanol (3.40 g, 70 %) as a white solid.

Reference： [1]Patent: WO2010/114181,2010,A1 .Location in patent: Page/Page column 105

17
[ 1187173-43-8 ]
[ 94108-56-2 ]
[ 1349643-60-2 ]

Yield	Reaction Conditions	Operation in experiment
57%	With triethylamine; In dichloromethane; for 20.0h;	2,7-Diazaspiro[4.5]decan-1 -one hydrogen chloride (80 mg, 0.420 mmol) was dissolved in dichloromethane (4 ml_). Then, triethylamine (0.1 17 ml_, 0.839 mmol) was added followed by 4-[(trifluoromethyl)oxy]benzenesulfonyl chloride (0.078 ml_, 0.462 mmol). After stirring for 20 h the reaction mixture was concentrated in vacuo and the resulting residue was purified by MDAP to give 7-({4-[(trifluoromethyl)oxy]- phenyl}sulfonyl)-2,7-diazaspiro[4.5]decan-1 -one (93 mg, 0.241 mmol, 57% yield) as a white solid. 1 H NMR (400 MHz, DMSO-d6) delta ppm 1.34 - 1 .47 (m, 2 H) 1.51 - 1 .64 (m, 1 H) 1.66 - 1.73 (m, 1 H) 1.90 - 1 .99 (m, 1 H) 2.00 - 2.08 (m, 1 H) 2.18 - 2.26 (m, 2 H) 3.19 (t, J=6.91 Hz, 2 H) 3.30 (s, 1 H) 3.62 (d, J=1 1 .35 Hz, 1 H) 7.64 (dd, J=8.85, 0.90 Hz, 2 H) 7.76 (s, 1 H) 7.86 - 7.90 (m, 2 H). MS ES+ve m/z 379 (M+H).

Reference： [1]Patent: WO2011/141728,2011,A1 .Location in patent: Page/Page column 26-27

18
[ 832710-65-3 ]
[ 94108-56-2 ]
[ 1349632-86-5 ]

Yield	Reaction Conditions	Operation in experiment
73%	With triethylamine; In dichloromethane; for 3h;	2,8-Diazaspiro[4.5]decan-1 -one hydrogen chloride (200 mg, 1.049 mmol) was dissolved in a mixture of dichloromethane (10 mL) and triethylamine (0.439 mL, 3.15 mmol), and 4-[(trifluoromethyl)oxy]benzenesulfonyl chloride (328 mg, 1 .259 mmol) was added. After 3 h, the reaction mixture was concentrated in vacuo, and the resulting residue was purified by silica column chromatography on SP4 (gradient elution: 0 - 20% MeOH - DCM) to give 8-({4-[(trifluoromethyl)oxy]phenyl}sulfonyl)-2,8- diazaspiro[4.5]decan-1 -one (300 mg, 0.769 mmol, 73% yield) as a white solid. 1 H NMR (400 MHz, DMSO-d6) delta ppm 1 .45 (ddd, J=13.47, 3.49, 3.32 Hz, 2 H) 1.62 - 1.71 (m, 2 H) 1.76 (t, J=6.77 Hz, 2 H) 2.57 - 2.65 (m, 2 H) 3.09 (t, J=6.77 Hz, 2 H) 3.43 - 3.51 (m, 2 H) 7.60 (s, 1 H) 7.64 (dd, J=8.91 , 0.90 Hz, 2 H) 7.87 - 7.92 (m, 2 H). MS ES+ve m/z 379 (M+H

Reference： [1]Patent: WO2011/141729,2011,A1 .Location in patent: Page/Page column 22-23

19
[ 1355052-37-7 ]
[ 94108-56-2 ]
[ 1355051-58-9 ]

Yield	Reaction Conditions	Operation in experiment
83%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 60℃; for 2h;	EXAMPLE 7Synthesis of (6-(4-(4-fluorophenoxy)phenyl)pyridin-2-yl)(4-((4-(trifluoromethoxy) phenyl)sulfonyl)piperazin-l-yl)methanone (compound 7)Scheme 157A 50 mL round bottom flask was charged with compound 6 (100 mg, 0.24 mmol), 4-trifluromethoxy sulfonyl chloride (41 mu, 0.24 mmol), DIEA (0.1 mL, 0.7 mmol) and DCM (5 mL). The mixture stirred at 60C for 2 h, cooled to room temperature, and extracted with EtOAc. The organic layer was separated and the solvent was removed by evaporation. The residue was subjected to column chromatography on silica gel (hexanes/EtOAc) to give compound 7 as a white solid (120 mg, 83% yield, (m/z + H) = 602, 1H NMR (CDC13) delta ppm: 6.80 - 8.90 (m, 15H); 3.8 (m, 4H); 3.20 (m, 4H)).

Reference： [1]Patent: WO2012/7836,2012,A1 .Location in patent: Page/Page column 86-87

20
[ 1376770-17-0 ]
[ 94108-56-2 ]
[ 1376770-35-2 ]

Yield	Reaction Conditions	Operation in experiment
82%	With triethylamine; In dichloromethane; at 20℃;	General procedure: In a solution of 6-(4-aminophenyl)-N-(3-(trifluoromethyl) phenyl) pyrimidin-4-amine (4) (1eq) in DCM (5ml), different substituted sulphonyl chlorides (l.1eq) and triethylamine (1.1eq) were added. Resulting reaction mixture was stirred at room temperature for 1-2 h and progress of reaction monitored by TLC in ethyl acetate- petroleum ether mixture. Resulting reaction mixture was diluted with DCM and water added. Organic layer washed by fresh water and brine, dried on Na2SO4 and concentrated under reduced pressure to afford crude product, which was purified by silica gel (100-200 No.) column chromatography in 10% ethyl acetate petroleum ether as eluent to obtain a title compound.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 3445 - 3448

21
[ 1412774-73-2 ]
[ 94108-56-2 ]
[ 1412776-46-5 ]

Yield	Reaction Conditions	Operation in experiment
77%	With triethylamine; In dichloromethane; at 20℃;	General procedure: 1-(5-(4-aminophenyl)-3-(3, 4-dimethoxyphenyl)-4, 5-dihydro-1H-pyrazol-1-yl) ethanone (3) (0.589 mmol) in DCM (10ml), different substituted sulphonyl chlorides (0.648 mmol) and triethylamine (0.648 mmol) were added. Resulting reaction mixture was stirred at room temperature for 1-2 h and progress of reaction monitored by TLC in ethyl acetate- petroleum ether mixture (3:7). Resulting reaction mixture was diluted with DCM and water added. Separated organic layer washed by fresh water and brine, dried on Na2SO4 and concentrated under reduced pressure to afford crude product, which was purified by silica gel (100-200 No.) flash column chromatography in ethyl acetate petroleum ether (30:70) as eluent to obtain a title compound. White solid, Yield 77%, mp 140-142 C; 1H NMR (CDCl3, 300MHz, delta ppm): 7.88 (s, 1H), 7.84 (d, 2H, J = 8.1 Hz), 7.42 (s, 1H), 7.26 (d, 2H, J = 12.9 Hz ), 7.13 (d, 1H, J = 7.5 Hz), 7.03 (d, 2H, J = 7.5 Hz), 6.87-6.85 (m, 3H), 5.57-5.54 (m, 1H), 3.98 (s, 3H), 3.95 (s, 3H), 3.78-3.69 (m, 1H), 3.1-3.05 (m, 1H), 2.48 (s, 3H); 13C NMR (DMSO-d6, 300MHz, delta ppm): 167.6, 154.6, 151.4, 152.2, 149.1, 139.1, 138.8, 136.6, 129.7 (2C), 130.2, 129.1, 126.9 (2C), 124.0, 121.9 (2C), 120.8 (2C), 111.8, 109.5, 59.3, 56.0, 55.9, 42.5, 22.1; IR (KBr) numax/cm-1 3317 (N-H str), 3181 (C-H), 1629 (C=O), 1462 (SO2NH), 1347 (C=N), 1237 (C-H), 1102 (C-N), 1089 (C-O); 932 (C-F); MS (APCI); m/z 564[M+H]+; HRMS (ESI): MH+, found 563.1345. C26H24F3N3O6S requires 563.1338; HPLC; 97%.

Reference： [1]Bioorganic and medicinal chemistry letters,2012,vol. 22,p. 6611 - 6615,5

22
[ 1423078-33-4 ]
[ 94108-56-2 ]
[ 1423077-95-5 ]

Yield	Reaction Conditions	Operation in experiment
91%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	[00200] (R)-N-(3-(10, l l-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-hydroxypropyl)-4- (trifluoromethoxy)benzenesulfonamide. A solution of (5 -l-amino-3-(10, l 1-dihydro- 5H-dibenzo[b,fJazepin-5-yl)propan-2-ol (0.100 g, 0.373 mmol) in DMF (1.0 mL) was cooled to 0 C and treated sequentially with triethylamine (52.0 mu?, 0.373 mmol) and 4-trifluoromethoxybenzenesulfonyl chloride (0.0970 g, 0.373 mmol). The solution was warmed to 25 C and stirred for 2 h. The mixture was poured over saturated aqueous NaCl (20 mL) and extracted with CH2CI2 (3 x 50 mL). The combined organic layers were washed with saturated aqueous NaCl (3 x 50 mL), dried (Na2S04), concentrated in vacuo, and the residue was purified by flash chromatography (Si02, 0-20% ethyl acetate-hexanes) to afford the title compound as a clear film (0.166 g, 91 %).
91%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of (S)-1-amino-3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-2-ol (0.100 g, 0.373 mmol) in DMF (1.0 mL) was cooled to 0 C and treated sequentially with triethylamine (52.0 L, 0.373 mmol) and 4-trifluoromethoxybenzenesulfonyl chloride (0.0970 g, 0.373 mmol). The solution was warmed to 25 C and stirred for 2 h. The mixture was poured over saturated aqueous NaCl (20 mL) and extracted with CH2Cl2 (3 50 mL). The combined organic layers were washed with saturated aqueous NaCl (3 50 mL), dried (Na2SO4), concentrated in vacuo, and the residue was purified by flash chromatography (SiO2, 0-20% ethyl acetate-hexanes) to afford the title compound as a white solid (0.166 g, 91%). mp. 120-121 C (ethyl acetate-hexanes); mp. 121-122 C (ethyl acetate-hexanes); []D = -20 (CH2Cl2, c = 1.0);1H NMR (600 MHz, CDCl3) 7.95 (2H, d, J = 8.4 Hz), 7.39 (2H, d, J = 8.4 Hz), 7.25 (2H, t, J = 7.8 Hz), 7.24 (2H, d, J = 6.0 Hz), 7.16 (2H, d, J = 7.8 Hz), 7.10 (2H, t, J = 6.6 Hz), 5.22 (1H, br s), 3.98 (1H, br s), 3.96 (1H, d, J = 4.8 Hz), 3.81 (1H, dd, J = 12.0, 7.2 Hz), 3.36 (1H, m), 3.26 (4H, m), 3.10 (1H, q, J = 7.2 Hz), 2.66 (1H, br s); 13C NMR (150 MHz, CDCl3) 152.3, 150.6, 147.8, 138.2, 134.3, 130.4, 129.3, 127.0, 123.8, 121.2, 119.8, 67.0, 54.2, 46.6, 32.2; LCMS m/z 493.1385 ([M + H+], C24H23F3N2O4S requires 493.1403). Analysis Calculated for C24H23F3N2O4S: C, 58.53; H, 4.71; N, 5.69, S, 6.51. Found: C, 58.82; H, 4.85; N, 5.28; S, 7.13.

Reference： [1]Patent: WO2013/25882,2013,A2 .Location in patent: Paragraph 00200
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6528 - 6534

23
[ 1423078-40-3 ]
[ 94108-56-2 ]
[ 1423077-99-9 ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	[00214] N-(4-(10,l l-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)cyclohexyl)-4- (trifluoromethoxy)benzenesulfonamide. A solution of 4-(10,l l-dihydro-5H- dibenzo[a,d][7]annulen-5-ylidene)cyclohexanamine (0.0800 g, 0.276 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with triethylamine (38.0 0.276 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (46.0 mu?, 0.276 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2CI2 (100 mL). The organic layer was washed with saturated aqueous NaCl (2 x 50 mL), dried (Na2S04), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2CI2 and purified by flash chromatography (S1O2, 0-20% ethyl acetate-hexanes) to afford the title compound (0.113 g, 80%) as a white solid. 1H NMR (600 MHz, CDC13) delta (as a mixture of rotamers) [2H, 8.03 (dd, J= 8.4, 1.8 Hz), 7.98 (dd, J= 9.0, 2.4 Hz)], [2H, 7.35 (d, J = 8.4 Hz), 7.34 (d, J= 9.0, 2.4 Hz)], 7.14-7.16 (4H, m), 7.09 (2H, m), 7.04 (2H, t, J = 7.8 Hz), [1H, 5.36 (t, J= 12 Hz), 5.09 (t, J= 9.0, 2.4 Hz)], 3.47 (1H, br s), 3.34-3.39 (2H, m), 2.81-2.85 (2H, m), 2.52-2.58 (2H, m), 2.08 (1H, t, J= 12.4 Hz), 1.96 (1H, t, J= 13.0 Hz), 1.85-1.91 (1H, m), 1.81 (1H, d, J= 9.4 Hz), 1.55 (1H, q, J= 11.0 Hz), 1.20 (1H, q, J= 11.4 Hz); LCMS m/z 514.2000 ([M + H+], C28H26F3NO3S requires 514.1658).
80%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of 4-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)cyclohexanamine (0.0800 g, 0.276 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with triethylamine (38.0 L, 0.276 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (46.0 L, 0.276 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2Cl2 (100 mL). The organic layer was washed with saturated aqueous NaCl (2 50 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-20% ethyl acetate-hexanes) to afford the title compound (0.113 g, 80%) as a white solid. 1H NMR (600 MHz, CDCl3) (as a mixture of rotamers) [2H, 8.03 (dd, J = 8.4, 1.8 Hz), 7.98 (dd, J = 9.0, 2.4 Hz)], [2H, 7.35 (d, J = 8.4 Hz), 7.34 (d, J = 9.0, 2.4 Hz)], 7.14-7.16 (4H, m), 7.09 (2H, m), 7.04 (2H, t, J = 7.8 Hz), [1H, 5.36 (t, J = 7.2 Hz), 5.09 (t, J = 9.0, 2.4 Hz)], 3.47 (1H, br s), 3.34-3.39 (2H, m), 2.81-2.85 (2H, m), 2.52-2.58 (2H, m), 2.08 (1H, t, J = 12.4 Hz), 1.96 (1H, t, J = 13.0 Hz), 1.85-1.91 (1H, m), 1.81 (1H, d, J = 9.4 Hz), 1.55 (1H, q, J = 11.0 Hz), 1.20 (1H, q, J = 11.4 Hz); LCMS m/z 514.2 ([M + H+], C28H26F3NO3S requires 514.2).

Reference： [1]Patent: WO2013/25882,2013,A2 .Location in patent: Paragraph 00214
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6528 - 6534

24
[ 1082712-62-6 ]
[ 94108-56-2 ]
[ 1423077-65-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	[00142] A solution of 2-(10H-phenothiazin-10-yl)ethanamine hydrochloride (0.080 g, 0.287 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with triethylamine (84.0 mu?, 0.603 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (0.082 g, 0.316 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (100 mL), and CH2CI2 (100 mL). The organic layer was washed with saturated aqueous NaCl (3 x 100 mL), dried (Na2S04), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2C12 and purified by flash chromatography (Si02, 0-25% ethyl acetate -hexanes) to afford the title compound as a clear film (0.121 g, 90%). 1H NMR (600 MHz, CDC13) delta 7.70 (2H, d, J= 8.4 Hz), 7.19 (2H, d, J= 7.8 Hz), 7.10 (2H, t, J= 7.2 Hz), 7.06 (2H, t, J = 7.8 Hz), 6.97 (2H, m), 6.74 (2H, d, J= 7.8 Hz), 5.00 (1H, s), 3.98 (2H, s), 3.34 (2H, d, J= 5.4 Hz); 13C NMR (150 MHz, CDCI3) delta 152.0, 144.4, 137.8, 129.0, 128.0, 127.7, 126.9, 123.7, 120.8, 119.5, 116.1, 46.0, 39.6; LCMS m/z 467.0703 ([M + H+], C2iHi7F3N203S2 requires 467.0705).

Reference： [1]Patent: WO2013/25882,2013,A2 .Location in patent: Paragraph 00142

25
[ 1423078-09-4 ]
[ 94108-56-2 ]
[ 1423077-61-5 ]

Yield	Reaction Conditions	Operation in experiment
67%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	[00137] A solution of 2-(2-chloro-10H-phenothiazin-10-yl)ethanamine hydrochloride (0.090 g, 0.287 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with Et3N (84.0 mu?, 0.603 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (0.082 g, 0.316 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (100 mL), and CH2CL (100 mL). The organic layer was washed with saturated aqueous NaCl (3 chi 100 mL), dried (Na2S04), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2CI2 and purified by flash chromatography (S1O2, 0-25% hexanes-Ethyl acetate) to afford the title compound as a clear film (0.096 g, 67%). ? NMR (600 MHz, CDCI3) delta 7.74 (2H, d, J= 8.8 Hz), 7.18 (1H, d, J= 7.6 Hz), 7.12 (3 H, m), 7.08 (1H, d, J= 8.2 Hz), 6.99 (1H, br s), 6.96 (1H, br s), 6.75 (1H, d, ./= 7.4 Hz), 6.73 (1H, br s), 4.85 (1H, t, J = 5.3 Hz), 3.97 (2H, br s), 3.36 (2H, dd, .7= 11.1, 5.5 Hz), 3.92 (2H, t, J= 5.8 Hz), 3.36 (2H, dd, J= 11.6, 5.8 Hz); l3C NMR (150 MHz, CDC13) delta 151.5, 145.1, 143.1, 137.1, 133.1, 129.6, 128.4, 127.9, 127.49, 127.2, 125.9, 124.6, 123.4, 122.9.120.1, 115.8, 115.7, 45.6, 38.8; LCMS m/z 500.9960 ([M + H ], C2, H16CIF3N2O3S2 requires 501.0316).
67%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of 2-(2-chloro-10H-phenothiazin-10-yl)ethanamine hydrochloride (0.090 g, 0.287 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with triethylamine (84.0 muL, 0.603 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (0.082 g, 0.316 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (100 mL), and CH2Cl2 (100 mL). The organic layer was washed with saturated aqueous NaCl (3 100 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-25% ethyl acetate-hexanes) to afford the title compound as a clear film (0.096 g, 67%). 1H NMR (600 MHz, CDCl3) 7.74 (2H, d, J = 8.8 Hz), 7.18 (1H, d, J = 7.6 Hz), 7.12 (3H, m), 7.08 (1H, d, J = 8.2 Hz), 6.99 (1H, br s), 6.96 (1H, br s), 6.75 (1H, d, J = 7.4 Hz), 6.73 (1H, br s), 4.85 (1H, t, J = 5.3 Hz), 3.97 (2H, br s), 3.36 (2H, dd, J = 11.1, 5.5 Hz), 3.92 (2H, t, J = 5.8 Hz), 3.36 (2H, dd, J = 11.6, 5.8 Hz); 13C NMR (150 MHz, CDCl3) 151.5, 145.1, 143.1, 137.1, 133.1, 129.6, 128.4, 127.9, 127.49, 127.2, 125.9, 124.6, 123.4, 122.9, 120.1, 115.8, 115.7, 45.6, 38.8; LCMS m/z 501.0 ([M + H+], C21H16ClF3N2O3S2 requires 501.0).

Reference： [1]Patent: WO2013/25882,2013,A2 .Location in patent: Paragraph 00137
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6528 - 6534

26
[ 1423077-51-3 ]
[ 94108-56-2 ]
[ 1423077-56-8 ]

Yield	Reaction Conditions	Operation in experiment
81%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	[00128] A solution of 2-(3-chloro-10,l l-dihydro-5H-dibenzo[b,f]azepin-5- yl)ethanamine hydrochloride (0.0800 g, 0.259 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with Et3N (75.0 mu?, 0.543 mmol), and 4- trifluoromethoxybenzenesulfonyl chloride (0.0740 g, 0.284 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2CI2 (100 mL). The organic layer was washed with saturated aqueous NaCl (2 x 50 mL), dried ( a2SC>4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CLLCL and purified by flash chromatography (Si02) 0-20% hexanes-Ethyl acetate) to afford the title compound as a white solid (0.0859 g, 81%). ? NMR (600 MHz, CDCI3) delta 7.74 (2H, d, J= 8.6 Hz), 7.18 (2H, d, J= 8.3 Hz), 7.10 (3H, m), 6.98 (2H, m), 6.94 (2H, d,J= 8.1 Hz), 6.93 (1H, s), 6.89 (1H, d, J= 8.1 Hz), 4.70 (1H, t, ./= 5.3 Hz), 3.81 (2H, t, J= 5.6 Hz), 3.16 (2H, dd, 11.4, 5.6 Hz), 3.07 (4H, m); l3C NMR (150 MHz, CDC13) delta 152.2, 148.0, 146.6, 137.99, 137.97, 135.1, 132.0, 131.74, 131.70, 130.0, 129.1, 127.0, 124.4, 123.2, 120.9, 120.3, 119.7, 49.5, 40.8, 32.2, 31.6; LCMS mlz 497.0918 ([M + H+], C23H2oClF3N203S requires 497.0918).
81%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of 2-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)ethanamine hydrochloride (0.0800 g, 0.259 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with triethylamine (75.0 L, 0.543 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (0.0740 g, 0.284 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2Cl2 (100 mL). The organic layer was washed with saturated aqueous NaCl (2 50 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-20% ethyl acetate-hexanes) to afford the title compound as a white solid (0.0859 g, 81%). 1H NMR (600 MHz, CDCl3) 7.74 (2H, d, J = 8.6 Hz), 7.18 (2H, d, J = 8.3 Hz), 7.10 (3H, m), 6.98 (2H, m), 6.94 (2H, d, J = 8.1 Hz), 6.93 (1H, s), 6.89 (1H, d, J = 8.1 Hz), 4.70 (1H, t, J = 5.3 Hz), 3.81 (2H, t, J = 5.6 Hz), 3.16 (2H, dd, 11.4, 5.6 Hz), 3.07 (4H, m); 13C NMR (150 MHz, CDCl3) 152.2, 148.0, 146.6, 137.99, 137.97, 135.1, 132.0, 131.74, 131.70, 130.0, 129.1, 127.0, 124.4, 123.2, 120.9, 120.3, 119.7, 49.5, 40.8, 32.2, 31.6; LCMS m/z 497.0918 ([M + H+], C23H20ClF3N2O3S requires 497.0918).

Reference： [1]Patent: WO2013/25882,2013,A2 .Location in patent: Paragraph 00128
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6528 - 6534

27
[ 94959-34-9 ]
[ 94108-56-2 ]
[ 1423077-68-2 ]

Yield	Reaction Conditions	Operation in experiment
92%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	[00147] A solution of 3-(9H-thioxanthen-9-ylidene)propan-l-amine hydrochloride (0.050 g, 0.173 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with triethylamine (50.0 mu?, 0.362 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (0.050 g, 0.190 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2C12 (100 mL). The organic layer was washed with saturated aqueous NaCl (2 x 50 mL), dried (Na2S04), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2C12 and purified by flash chromatography (Si02, 0-20% ethyl acetate - hexanes) to afford the title compound as a clear film (0.0756 g, 92%). 1H NMR (600 MHz, CDC13) delta 7.82 (2H, d, J= 8.4 Hz), 7.45 (1H, d, J= 7.2 Hz), 7.40 (1H, d, J= 7.2 Hz) 7.38 (1H, d, J= 7.2 Hz), 7.28 (1H, m), 7.23 (5H, m), 7.18 (2H, d, J = 8.4 Hz), 5.63 (1H, t, J= 7.2 Hz), 4.86 (1H, br m), 3.12 (2H, q, J= 6.6 Hz), 2.61 (2H, q, J= 6.6 Hz); 13C NMR (150 MHz, CDC13) delta 152.1, 138.6, 138.4, 138.1, 133.9, 133.1, 131.8, 129.3, 128.7, 127.6, 127.3, 127.2, 127.04, 127.01, 126.2, 126.0, 125.7, 121.2, 121.0, 43.2, 29.9; LCMS m/z 478.0750 ([M + H+], C23Hi8F3N03S2 requires 478.0753).
92%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of 3-(9H-thioxanthen-9-ylidene)propan-1-amine hydrochloride (0.050 g, 0.173 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with triethylamine (50.0 muL, 0.362 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (0.050 g, 0.190 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2Cl2 (100 mL). The organic layer was washed with saturated aqueous NaCl (2 50 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-20% ethyl acetate-hexanes) to afford the title compound as a clear film (0.0756 g, 92%). 1H NMR (600 MHz, CDCl3) 7.82 (2H, d, J = 8.4 Hz), 7.45 (1H, d, J = 7.2 Hz), 7.40 (1H, d, J = 7.2 Hz) 7.38 (1H, d, J = 7.2 Hz), 7.28 (1H, m), 7.23 (5H, m), 7.18 (2H, d, J = 8.4 Hz), 5.63 (1H, t, J = 7.2 Hz), 4.86 (1H, br m), 3.12 (2H, q, J = 6.6 Hz), 2.61 (2H, q, J = 6.6 Hz); 13C NMR (150 MHz, CDCl3) 152.1, 138.6, 138.4, 138.1, 133.9, 133.1, 131.8, 129.3, 128.7, 127.6, 127.3, 127.2, 127.04, 127.01, 126.2, 126.0, 125.7, 121.2, 121.0, 43.2, 29.9; LCMS m/z 478.0750 ([M + H+], C23H18F3NO3S2 requires 478.0753).

Reference： [1]Patent: WO2013/25882,2013,A2 .Location in patent: Paragraph 00147
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6528 - 6534

28
3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)propan-1-amine hydrochloride [ No CAS ]
[ 94108-56-2 ]
[ 1423077-70-6 ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	[00151] A solution of 3-(10,l l-dihydro-SH-dibenzofa^^annulen-S- ylidene^ropan-l-amine hydrochloride (0.150 g, 0.524 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with triethylamine (152 mu?^, 1.10 mmol), and 4- trifluoromethoxybenzenesulfonyl chloride (0.150 g, 0.577 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2C12 (100 mL). The organic layer was washed with saturated aqueous NaCl (2 x 50 mL), dried (Na2S04), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2C12 and purified by flash chromatography (Si02, 0-20% ethyl acetate-hexanes) to afford the title compound as a white solid (0.214 g, 86%). 1H NMR (600 MHz, CDC13) delta 7.79 (2H, d, J= 8.4 Hz), 7.20 (2H, d, J= 8.4 Hz), 7.19 (3H, d, J= 4.2 Hz), 7.08-7.14 (3H, m), 7.00 (2H, t, J = 10.2 Hz), 5.68 (1H, t, J= 7.8 Hz), 4.67 (1H, t, J= 6.0 Hz), 3.28 (2H, br m), 3.01 (2H, br m), 2.94 (1H, br m), 2.76 (1H, br s), 2.27 (2H, br s); 13C NMR (150 MHz, CDC13) delta 152.2, 146.2, 140.7, 139.6, 139.4, 138.4, 137.2, 130.3, 129.3, 128.6, 128.4, 128.2, 127.9, 127.6, 126.6, 126.3, 126.1, 121.3, 121.1, 43.2, 33.9, 32.2, 29.8; LCMS m/z 474.1346 ([M + H+], C25H22F3N03S requires 474.1345).
86%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of 3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)propan-1-amine hydrochloride (0.150 g, 0.524 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with triethylamine (152 muL, 1.10 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (0.150 g, 0.577 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2Cl2 (100 mL). The organic layer was washed with saturated aqueous NaCl (2 50 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-20% ethyl acetate-hexanes) to afford the title compound as a white solid (0.214 g, 86%).1H NMR (600 MHz, CDCl3) 7.79 (2H, d, J = 8.4 Hz), 7.20 (2H, d, J = 8.4 Hz), 7.19 (3H, d, J = 4.2 Hz), 7.08-7.14 (3H, m), 7.00 (2H, t, J = 10.2 Hz), 5.68 (1H, t, J = 7.8 Hz), 4.67 (1H, t, J = 6.0 Hz), 3.28 (2H, br m), 3.01 (2H, br m), 2.94 (1H, br m), 2.76 (1H, br s), 2.27 (2H, br s); 13C NMR (150 MHz, CDCl3) 152.2, 146.2, 140.7, 139.6, 139.4, 138.4, 137.2, 130.3, 129.3, 128.6, 128.4, 128.2, 127.9, 127.6, 126.6, 126.3, 126.1, 121.3, 121.1, 43.2, 33.9, 32.2, 29.8; LCMS m/z 474.1346 ([M + H+], C25H22F3NO3S requires 474.1345).

Reference： [1]Patent: WO2013/25882,2013,A2 .Location in patent: Paragraph 00151
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6528 - 6534

29
[ 129717-37-9 ]
[ 94108-56-2 ]
[ 1423077-75-1 ]

Yield	Reaction Conditions	Operation in experiment
62%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	[00163] A solution of N1-(10,l l-dihydro-5H-dibenzo[a,d][7]annulen-5-yl)ethane- 1,2-diamine (0.050 g, 0.198 mmol) in DMF (1.0 mL) was cooled to 0 C and treated sequentially with triethylamine (30.0 mu?, 0.217 mmol) and 4- trifluoromethoxybenzenesulfonyl chloride (0.0520 g, 0.198 mmol). The solution was warmed to 25 C and stirred for 2 h. The mixture was poured over saturated aqueous NaCl (20 mL) and extracted with CH2CI2 (3 x 50 mL). The combined organic layers were washed with saturated aqueous NaCl (3 x 50 mL), dried (Na2S04), concentrated in vacuo, and the residue was purified by flash chromatography (Si02, 0-20% ethyl acetate -hexanes) to afford the title compound as a clear film (0.0584 g, 62%). 1H NMR (600 MHz, CDCI3) delta 7.79 (2H, d, J= 9.0 Hz), 7.25 (2H, d, J= 9.0 Hz), 7.19 (2H, m), 7.12 (2H, m), 5.11 (1H, br s), 4.67 (1H, s), 3.62 (2H, d, J= 6.0 Hz), 2.92 (4H, q, J= 5.4 Hz), 2.68 (2H, t, J= 5.4 Hz), 1.63 (1H, br s); 13C NMR (150 MHz, CDC13) 5 152.11, 152.10, 140.1, 139.5, 138.3, 130.8, 129.7, 129.3, 128.0, 126.2, 121.1, 69.9, 47.0, 43.1, 32.6; LCMS m/z 477.1399 ([M + H+], C24H23F3N203S requires 477.1454).
62%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of N1-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-yl)ethane-1,2-diamine(0.050 g, 0.198 mmol) in DMF (1.0 mL) was cooled to 0 C and treated sequentially with triethylamine (30.0 L, 0.217 mmol) and 4-trifluoromethoxybenzenesulfonyl chloride (0.0520 g, 0.198 mmol). The solution was warmed to 25 C and stirred for 2 h. The mixture was poured over saturated aqueous NaCl (20 mL) and extracted with CH2Cl2 (3 50 mL). The combined organic layers were washed with saturated aqueous NaCl (3 50 mL), dried (Na2SO4), concentrated in vacuo, and the residue was purified by flash chromatography (SiO2, 0-20% ethyl acetate-hexanes) to afford the title compound as a clear film (0.0584 g, 62%). 1H NMR (600 MHz, CDCl3) 7.79 (2H, d, J = 9.0 Hz), 7.25 (2H, d, J = 9.0 Hz), 7.19 (2H, m), 7.12 (2H, m), 5.11 (1H, br s), 4.67 (1H, s), 3.62 (2H, d, J = 6.0 Hz), 2.92 (4H, q, J = 5.4 Hz), 2.68 (2H, t, J = 5.4 Hz), 1.63 (1H, br s); 13C NMR (150 MHz, CDCl3) 152.11, 152.10, 140.1, 139.5, 138.3, 130.8, 129.7, 129.3, 128.0, 126.2, 121.1, 69.9, 47.0, 43.1, 32.6; LCMS m/z 477.1 ([M + H+], C24H23F3N2O3S requires 477.1).

Reference： [1]Patent: WO2013/25882,2013,A2 .Location in patent: Paragraph 00163
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6528 - 6534

30
[ 1423078-22-1 ]
[ 94108-56-2 ]
[ 1423077-77-3 ]

Yield	Reaction Conditions	Operation in experiment
89%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	[00167] A solution of l-amino-3-(3-chloro-10,l l-dihydro-5H-dibenzo[b,f]azepin-5- yl)propan-2-ol (0.100 g, 0.330 mmol) in DMF (1.0 mL) was cooled to 0 C and treated sequentially with triethylamine (45.0 mu?, 0.330 mmol) and 4- trifluoromethoxybenzenesulfonyl chloride (0.0860 g, 0.330 mmol). The solution was warmed to 25 C and stirred for 2 h. The mixture was poured over saturated aqueous NaCl (20 mL) and extracted with CH2CI2 (3 x 50 mL). The combined organic layers were washed with saturated aqueous NaCl (3 x 50 mL), dried (Na2S04), concentrated in vacuo, and the residue was purified by flash chromatography (Si02, 0-20% ethyl acetate -hexanes) to afford the title compound as a clear film (0.155 g, 89%). 1H NMR (600 MHz, CDCI3) delta 7.95 (2H, d, J= 7.2 Hz), 7.40 (2H, d, J= 8.4 Hz), 7.28 (1H, t, J = 7.2 Hz), 7.26 (1H, d, J= 7.8 Hz), 7.13-7.17 (4H, m), 7.05 (1H, d, J= 7.8 Hz), 5.21 (1H, br s), 3.97 (1H, br s), 3.91 (1H, dd, J= 12.6, 3.6 Hz), 3.78 (1H, dd, J= 12.6, 7.8 Hz), 3.36 (1H, m), 3.22 (4H, d, J= 4.8 Hz), 3.09 (1H, quintet, J= 6.6 Hz), 2.56 (1H, br s); 13C NMR (150 MHz, CDCI3) delta 152.3, 148.6, 147.3, 141.2, 138.1, 134.9, 132.0, 131.9, 131.8, 130.2, 129.3, 127.2, 124.5, 123.5, 121.2, 120.3, 119.9, 67.0, 54.3, 46.6, 32.0, 31.6; LCMS m/z 527.1056 ([M + H+], C24H22C1F3N204S requires 527.1014).

Reference： [1]Patent: WO2013/25882,2013,A2 .Location in patent: Paragraph 00167

31
[ 1423078-24-3 ]
[ 94108-56-2 ]
[ 1423077-79-5 ]

Yield	Reaction Conditions	Operation in experiment
91%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	[00172] A solution of l-amino-3-(10,l l-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan- 2-ol (0.100 g, 0.373 mmol) in DMF (1.0 mL) was cooled to 0 C and treated sequentially with triethylamine (52.0 0.373 mmol) and 4- trifluoromethoxybenzenesulfonyl chloride (0.0970 g, 0.373 mmol). The solution was warmed to 25 C and stirred for 2 h. The mixture was poured over saturated aqueous NaCl (20 mL) and extracted with CH2C12 (3 x 50 mL). The combined organic layers were washed with saturated aqueous NaCl (3 x 50 mL), dried (Na2S04), concentrated in vacuo, and the residue was purified by flash chromatography (Si02, 0-20%> ethyl acetate -hexanes) to afford the title compound as a clear film (0.166 g, 91%). Mp. 102- 103 C (white needles, ether-hexanes); 1H NMR (600 MHz, CDC13) delta 7.95 (2H, d, J= 8.4 Hz), 7.39 (2H, d, J= 8.4 Hz), 7.25 (2H, t, J= 7.8 Hz), 7.24 (2H, d, J= 6.0 Hz), 7.16 (2H, d, J= 7.8 Hz), 7.10 (2H, t, J= 6.6 Hz), 5.22 (1H, br s), 3.98 (1H, br s), 3.96 (1H, d, J= 4.8 Hz), 3.81 (1H, dd, J= 12.0, 7.2 Hz), 3.36 (1H, m), 3.26 (4H, m), 3.10 (1H, q, J= 7.2 Hz), 2.66 (1H, br s); 13C NMR (150 MHz, CDC13) delta 152.3, 150.6, 147.8, 138.2, 134.3, 130.4, 129.3, 127.0, 123.8, 121.2, 119.8, 67.0, 54.2, 46.6, 32.2; LCMS m/z 443.1492 ([M + H+], C23H23C1N203S requires 443.1191). Anal. Calcd for C23H23C1N203S: C, 58.53; H, 4.71; N, 5.69, S, 6.51. Found: C, 58.41; H, 4.87; N, 6.01; S, 7.01.

Reference： [1]Patent: WO2013/25882,2013,A2 .Location in patent: Paragraph 00172

32
[ 1423077-08-0 ]
[ 94108-56-2 ]
[ 1423077-49-9 ]

Yield	Reaction Conditions	Operation in experiment
84%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine hydrochloride (1.00 g, 3.09 mmol) in DMF (10.0 mL) was cooled to 0 C, treated with Et3N (0.90 mL, 6.50 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (0.58 mL, 3.40 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (100 mL), and CH2Cl2 (300 mL). The organic layer was washed with saturated aqueous NaCl (2 100 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-25% hexanes-ethyl acetate). The purified fractions were combined, dissolved in a minimal amount of ethyl ether, and could either be recrystallized or precipitated with the addition of hexanes to afford the title compound as a white solid (1.33 g, 84%). mp. 119-121 C (ether-hexanes); 1H NMR (600 MHz, CDCl3) 7.76 (2H, d, J = 8.8 Hz), 7.24 (2H, d, J = 8.5 Hz), 7.12 (1H, t, J = 7.6 Hz), 7.10 (1H, d, J = 7.7 Hz), 6.98 (2H, d, J = 7.6 Hz), 6.97 (1H, d, J = 8.1 Hz), 6.95 (1H, s), 6.88 (1H, dd, J = 8.2, 1.7 Hz), 4.66 (1H, t, J = 6.1 Hz), 3.68 (1H, t, J = 6.3 Hz), 3.02 (4H, br s), 3.00 (2H, q, J = 6.5 Hz), 1.72 (2H, quintet, J = 6.5 Hz); 13C NMR (150 MHz, CDCl3) 151.6, 148.1, 146.8, 137.7, 134.4, 131.2, 131.1, 130.9, 129.3, 128.6, 126.3, 123.3, 122.1, 120.44, 120.43, 119.7, 119.1, 46.8, 40.7, 31.4, 40.8, 26.4; HRMS-QTOF m/z 511.1064 ([M + H+], C24H22ClF3N2O3S requires 511.1065). Analysis Calculated for C24H22ClF3N2O3S: C, 56.42; H, 4.34; N, 5.48, S, 6.28. Found: C, 56.15; H, 4.59; N, 5.60; S, 6.24.
68%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	[00121] A solution of 3-(3-chloro-10, 11 -dihydro-5H-dibenzo[6/]azepin-5-yl)propan- 1 -amine hydrochloride (0.0800 g, 0.247 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with Et3N (72.0 muL·, 0.520 mmol), and 4-trifIuoromethoxybenzenesuIfonyl chloride (0.0700 g, 0.272 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCI (50 mL), and CH2CI2 (100 mL). The organic layer was washed with saturated aqueous NaCI (2 x 50 mL), dried ( a2S04), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2CI2 and purified by flash chromatography (Si02, 0-25% hexanes-Ethyl acetate) to afford the title compound as a white solid (0.0860 g, 68%). Mp.11 -121 C (ether-hexanes); ? NMR (600 MHz, CDCI3) delta 7.76 (2H, d, J= 8.8 Hz), 7.24 (2H, d, J= 8.5 Hz), 7.12 (1H, t, J= 7.6 Hz), 7.10 (1H, d,J= 7.7 Hz), 6.98 (2H, d, J= 7.6 Hz), 6.97 (1H, d, J= 8.1 Hz), 6.95 (1 H, s), 6.88 (1H, dd, J = 8.2, 1.7 Hz), 4.66 (1 H, t, J= 6.1 Hz), 3.68 (1H, t, J= 6.3 Hz), 3.02 (4H, br s), 3.00 (2H, q, J= 6.5 Hz), 1.72 (2H, quintet, J=6.5 Hz); l3C MR (600 MHz, CDC13) delta 151.6, 148.1, 146.8, 137.7, 134.4, 131.2, 131.1, 130.9, 129.3, 128.6, 126.3, 123.3, 122.1, 120.44, 120.43, 119.7, 119.1, 46.8, 40.7, 31.4, 40.8, 26.4; LCMS m/z 511.0821 (fM + H+], C24H22CIF3N2O3S requires 511.1065). Anal. Calcd for C24H22CIF3N2O3S: C, 56.42; H, 4.34; N, 5.48, S, 6.28. Found: C, 56.15; H, 4.59; N, 5.60; S, 6.24.

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6528 - 6534
[2]Patent: WO2013/25882,2013,A2 .Location in patent: Paragraph 00121

33
[ 1423078-26-5 ]
[ 94108-56-2 ]
[ 1423077-86-4 ]

Yield	Reaction Conditions	Operation in experiment
59%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	[00182] N-(3-(l 0, 11 -dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-methylpropyl)-4- (trifluoromethoxy)benzenesulfonamide. A solution of 3-(10,l l-dihydro-5H- dibenzo[b,f]azepin-5-yl)-2-methylpropan-l-amine hydrochloride (0.100 g, 0.330 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with triethylamine (96.1 mu?, 0.693 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (61.4 mu?^, 0.363 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2CI2 (100 mL). The organic layer was washed with saturated aqueous NaCl (2 x 50 mL), dried (Na2S04), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2CI2 and purified by flash chromatography (S1O2, 0-20% ethyl acetate -hexanes) to afford the title compound as a clear film (0.0948 g, 59%). 1H NMR (600 MHz, CDCI3) delta 7.74 (2H, d, J= 9.0 Hz), 7.24 (2H, d, J= 8.4 Hz), 7.10-7.13 (4H, m), 6.99 (2H, d, J = 7.8 Hz), 6.95 (2H, d, J= 7.2 Hz), 4.94 (1H, t, J= 6.6 Hz), 3.66 (1H, dd, J= 13.2, 6.0 Hz), 3.40 (1H, dd, J= 13.2, 8.4 Hz), 3.10 (4H, s), 3.07 (1H, q, J = 5.4 Hz), 2.85 (1H, quintet, J= 6.6 Hz), 1.94 (1H, sextet, J= 6.0 Hz), 0.93 (3H, d, J= 6.6 Hz); 13C NMR (150 MHz, CDCI3) delta 152.11, 152.10, 148.2, 138.5, 134.2, 130.3, 129.3, 126.7, 123.2, 121.1, 119.7, 54.8, 47.8, 32.1, 31.1, 25.5; LCMS m/z 491.2506 ([M + H+], C25H25F3N203S requires 491.1611).
59%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-methylpropan-1-amine hydrochloride (0.100 g, 0.330 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with triethylamine (96.1 L, 0.693 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (61.4 L, 0.363 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2Cl2 (100 mL). The organic layer was washed with saturated aqueous NaCl (2 50 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-20% ethyl acetate-hexanes) to afford the title compound as a clear film (0.0948 g, 59%). 1H NMR (600 MHz, CDCl3) 7.74 (2H, d, J = 9.0 Hz), 7.24 (2H, d, J = 8.4 Hz), 7.10-7.13 (4H, m), 6.99 (2H, d, J = 7.8 Hz), 6.95 (2H, d, J = 7.2 Hz), 4.94 (1H, t, J = 6.6 Hz), 3.66 (1H, dd, J = 13.2, 6.0 Hz), 3.40 (1H, dd, J = 13.2, 8.4 Hz), 3.10 (4H, s), 3.07 (1H, q, J = 5.4 Hz), 2.85 (1H, quintet, J = 6.6 Hz), 1.94 (1H, sextet, J = 6.0 Hz), 0.93 (3H, d, J = 6.6 Hz); 13C NMR (150 MHz, CDCl3) 152.11, 152.10, 148.2, 138.5, 134.2, 130.3, 129.3, 126.7, 123.2, 121.1, 119.7, 54.8, 47.8, 32.1, 31.1, 25.5; LCMS m/z 491.3 ([M + H+], C25H25F3N2O3S requires 491.2).

Reference： [1]Patent: WO2013/25882,2013,A2 .Location in patent: Paragraph 00182
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6528 - 6534

34
[ 94108-56-2 ]
[ 1428966-46-4 ]

Yield	Reaction Conditions	Operation in experiment
82%	With dmap; hydroxylamine hydrochloride; In pyridine; at 20℃; for 0.0833333h;Cooling with ice;	General procedure: To a mixture of hydroxylamine hydrochloride (2 equiv.) and DMAP (2 equiv.) in pyridine (20 mL) was added a portion of arylsulfonyl chloride (1 equiv.) on an ice-bath. Then, the mixture was stirred for 5 min at room temperature. The resulting suspension was poured into AcOEt (100 mL) and 1 N HCl aq. (100 mL). The AcOEt layer was separated, washed with brine (100 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography under one of the gradient conditions indicated below, and recrystallized from Et2O/n-hexane to give N-hydroxyarylsulfonamide derivatives.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 2340 - 2343

35
[ 1460737-83-0 ]
[ 94108-56-2 ]
[ 1460737-94-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine; In ethanol; dichloromethane; at 20℃;Inert atmosphere;	General procedure: To a solution of amine 4 (0.67 g, 1.5 mmol) in DCM/EtOH (150 mL, 4:1) was added triethylamine (0.4 mL, 3.0 mmol) and the appropriate aroyl or benzenesulfonyl halide (1.2 mmol). The mixture was stirred at room temperature under argon for several hours depending on the completion of the reaction,which was checked by tlc. After evaporation of solvent under vacuum, the residue was purified by silica gel chromatography and recrystallized from an appropriate solvent to give the title products.

Reference： [1]Molecules,2013,vol. 18,p. 7557 - 7569

36
[ 1380228-73-8 ]
[ 94108-56-2 ]
[ 1380228-89-6 ]

Yield	Reaction Conditions	Operation in experiment
87%	With pyridine; In dichloromethane; at 50℃; for 2h;	The 2,6-difluoro-N1-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)benzene-1,3-diamine(20 mg, 0.047 mmol) prepared at Step 9 was added and dissolved into dichloromethane solvent. <strong>[94108-56-2]4-(trifluoromethoxy)benzenesulfonyl chloride</strong> (18 mg, 0.07 mmol) and pyridine (8 uL, 0.094 mmol) were added into the reaction solution and stirred at 50C for 2 hours. After the reaction, the reactant was washed with 1N aqueous hydrochloric acid solution and salt water. After extraction with dichloromethane, the organic layer was dried with sulfuric anhydride magnesium and vacuum concentrated, and then refined by means of column chromatography, so that 26 mg of the target compound, N-(2,4-difluoro-3-(3-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)-4-(trifluoromethoxy)benzenesulfonamide (percentage yield: 87%), was obtained.1H NMR(400MHz, CDCl3): delta 11.51(s, 1H), 9.62(dd, J = 8.0, 1.6 Hz, 1H), 8.98(s, 1H), 8.39(s, 1H), 8.17(dd, J = 4.8, 2.0 Hz, 1H), 7.84(m, 2H), 7.40(m, 1H), 7.29(m, 2H), 6.97(m, 3H), 5.89(dd, J = 10.4, 2.0 Hz, 1H), 4.23(m, 1H), 3.85(m, 1H), 2.23-1.71(m, 6H).

Reference： [1]Patent: EP2647637,2013,A2 .Location in patent: Paragraph 0111

37
[ 1574389-02-8 ]
[ 94108-56-2 ]
[ 1574389-03-9 ]

Yield	Reaction Conditions	Operation in experiment
83.4%		Step 4 - Synthesis of compound N-{l-[7-Benzenesulfonyl-6-(l-methyl-lH-pyrazol-4-yl)-7H- pyrrolo[2,3-d]pyrimidin-4-yl]-piperidin-4-yl}-4-trifluoromethoxy-benzenesulfonamide (19): Compound 18 (0.1 g, 0.229 mmol) was taken up in tetrahydrofuran (80 eq., 1.483mL) and cooled to 0 C. Once completely dissolved, sodium hydride (1.5 eq., 0.008 mg) was added and the solution was stirred for 5 minutes before the addition of <strong>[94108-56-2]4-(trifluoromethoxy)benzenesulfonyl chloride</strong> (3 eq., 0.1 17 mL). After 2 hours the solution was diluted with water and extracted with ethyl acetate (3 x 100 mL). The organic layers were combined, washed with brine, dried over Na2S04, filtered, and concentrated under reduced pressure to give compound 19 (0.126 g, 83.4% yield).

Reference： [1]Patent: WO2014/39714,2014,A2 .Location in patent: Paragraph 0298

38
[ 94108-56-2 ]
[ 1513-45-7 ]

Yield	Reaction Conditions	Operation in experiment
88.5%	With ammonia; In methanol; at 20℃; for 1h;Inert atmosphere; Cooling with ice;	Ar under the protection, 4-trifluoromethoxybenzenesulfonyl chloride (520 mg, 2.0 mmol) Was added an excess of methanolic methanol solution (5 mL, 35 mmol) Ice bath to room temperature reaction, after 40min to stop the reaction, Steamed solution, add 20mL of ice water, DCM extracted four times, combined organic phase, Recrystallization gave a white solid (425 mg, 88.5%).
	With ammonium hydroxide; In acetonitrile; at 0 - 20℃; for 1h;Inert atmosphere;	General procedure: In a 50 ml RB flask, sulfonyl chloride (500 mg) was taken in acetonitrile (5 ml) and the solution was cooled to 0 deg. Cel. To this aqueous ammonia solution (1.5 ml) was added dropwise. RM was then stirred at RT for 1 hr. RM was evaporated to dryness and the residue was then trichirated with minimum water and suspension was filtered and solid was dried to get the sulfonamide as solid.

Reference： [1]Patent: CN107098846,2017,A .Location in patent: Paragraph 2501; 2503; 2504
[2]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 2222 - 2225
[3]Chemical Communications,2020,vol. 56,p. 5010 - 5013

39
3-(10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepin-5-yl)propan-1-amine [ No CAS ]
[ 94108-56-2 ]
N-(3-(10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepin-5-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of 3-(10,l l-dihydro-5H- benzo[b]pyrido[2,3-f]azepin-5-yl)propan-l-amine (0.060 g, 0.237 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with Et3N (36.0 0.261 mmol), and 4- trifluoromethoxybenzenesulfonyl chloride (42.0 0.249 mmol). The mixture was warmed to 25 C and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2C12 (100 mL). The organic layer was washed with saturated aqueous NaCl (3 x 50 mL), dried (Na2S04), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2C12 and purified by flash chromatography (Si02, 0-30% hexanes-ethyl acetate). The purified fractions were combined, dissolved in a minimal amount of ethyl acetate and were precipitated with the addition of hexanes to afford the title compound as a white solid (0.065 g, 57%>). 1H NMR (600 MHz, CDC13) delta 8.04 (1H, dd, J= 4.6, 1.0 Hz), 7.80 (2H, d, J= 7.2 Hz), 7.28 (1H, d, J= 7.8 Hz), 7.26 (2H, d, J= 9.0 Hz), 7.15-7.18 (2H, m), 7.02-7.04 (3H, m), 5.40 (1H, s), 3.75 (2H, t, J= 6.6 Hz), 3.19 (2H, t, J= 6.0 Hz), 3.04 (2H, t, J= 6.0 Hz), 3.00 (2H, t, J= 6.6 Hz), 1.78 (2H, t, J= 6.6 Hz); liC NMR (150 MHz, CDC13) delta 152.5, 152.2, 147.5, 144.2, 142.2, 138.5, 136.8, 129.5, 129.3, 127.1, 126.1, 124.5, 121.6, 121.4, 121.1, 120.8, 46.9, 41.0, 36.4, 30.1, 27.7; LCMS m/z 478.3604 ([M + H+], C23H22C1F3N303S requires 478.1407).
57%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of 3-(10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepin-5-yl)propan-1-amine (0.060 g, 0.237 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with Et3N (36.0 L, 0.261 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (42.0 L, 0.249 mmol). The mixture was warmed to 25 C and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2Cl2 (100 mL). The organic layer was washed with saturated aqueous NaCl (3 50 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-30% ethyl acetate-hexanes). The purified fractions were combined, dissolved in a minimal amount of ethyl acetate and were precipitated with the addition of hexanes to afford the title compound as a white solid (0.065 g, 57%). 1H NMR (600 MHz, CDCl3) 8.04 (1H, dd, J = 4.6, 1.0 Hz), 7.80 (2H, d, J = 7.2 Hz), 7.28 (1H, d, J = 7.8 Hz), 7.26 (2H, d, J = 9.0 Hz), 7.15-7.18 (2H, m), 7.02-7.04 (3H, m), 5.40 (1H, s), 3.75 (2H, t, J = 6.6 Hz), 3.19 (2H, t, J = 6.0 Hz), 3.04 (2H, t, J = 6.0 Hz), 3.00 (2H, t, J = 6.6 Hz), 1.78 (2H, t, J = 6.6 Hz); 13C NMR (150 MHz, CDCl3) 152.5, 152.2, 147.5, 144.2, 142.2, 138.5, 136.8, 129.5, 129.3, 127.1, 126.1, 124.5, 121.6, 121.4, 121.1, 120.8, 46.9, 41.0, 36.4, 30.1, 27.7; LCMS m/z 478.4 ([M + H+], C23H22ClF3N3O3S requires 478.1).

Reference： [1]Patent: WO2014/130534,2014,A1 .Location in patent: Paragraph 00107
[2]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6528 - 6534

40
1-amino-3-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yl)propan-2-ol [ No CAS ]
[ 94108-56-2 ]
N-(3-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yl)-2-hydroxypropyl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 18h;	A solution l-amino-3- (9, 10-dihydro-4H-benzo[4,5]cyclohepta[ 1 ,2-£]thiophen-4-yl)propan-2-ol (0.041 g, 0.150 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with Et3N (0.021 mL, 0.150 mmol), and 4-(trifluoromethoxy)benzene-l-sulfonyl chloride (0.025 mL, 0.150 mmol). The mixture was warmed to RT, and stirred for 18 h. The mixture was partitioned between water (10 mL) and CH2CI2 (10 mL). The organic layer was washed with saturated aqueous NaCl (30 mL x 3) to remove DMF, and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2CI2 and purified by flash chromatography (S1O2, 20%-50% ethylacetate-hexanes) to afford N-(3-(9,10- dihydro-4H-benzo[4,5]cyclohepta[l,2-]thiophen-4-yl)-2-hydroxypropyl)-4- (trifluoromethoxy)benzenesulfonamide (105) (0.065 g, 88%). The diastereomeric ratio was determined to be 1 : 1.2 by 1H NMR analysis. 1H NMR (600 MHz, CD3OD) delta 7.93-7.86 (2H, m), 7.42-7.37 (2H, m), 7.17-7.04 (5H, m), 1H [6.87 (d, J= 4.8 Hz), 6.81 (d, J= 5.4 Hz)], 1H [4.31 (dd, J= 11.4, 3.6 Hz), 4.27 (d, J= 9.0, 6.0 Hz)], 3.54- 3.17 (4H, m), 2.93-2.78 (5H, m), 1H [2.49-2.20 (m), 2.17-2.13 (m)], 1.82-1.78 (1H, m); 13C NMR (150 MHz, CD3OD) delta 151.7, 143.4, 141.2, 140.5, 140.3, 139.8, 139.7, 138.3, 137.0, 136.7, 130.6, 130.0, 129.9, 129.8, 129.0, 128.7, 126.8, 126.7, 126.4, 126.0, 121.1, 121.0, 120.8, 67.9, 67.6, 49.1, 48.7, 44.0, 43.7, 42.6, 42.4, 33.1, 32.8, 28.6; LCMS m/z 498.1076 ([M + H+], C23H23F3N04S2 requires 498.5577).

Reference： [1]Patent: WO2014/130534,2014,A1 .Location in patent: Paragraph 00121

41
[ 75-64-9 ]
[ 94108-56-2 ]
N-(tert-butyl)-4-(trifluoromethoxy)benzene-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	In tetrahydrofuran; at 0 - 20℃; for 3h;	Step 2: Synthesis of N- (tert-butyl)- 4- (trifluoromethoxy)benzene-sulfonamide. To a 500 mL round bottom flask equipped with a stirbar wasadded <strong>[94108-56-2]4-(trifluoromethoxy)benzene-1-sulfonyl chloride</strong>, (25 g, 95.9 mmol) and 100 mL of THF and the flask was cooled to 0C. Tert-butylamine (100 mL, 959 mmol, 10 eq) was dissolved in 100 mL of THF in an Erlenmeyer flask. The first 50 mL of the tert-butylamine solution was added dropwise to the sulfonylchloride solution with the remaining poured directly from the Erlenmeyer Flask. After the reaction was stirred for 2 hours in the ice bath, the bath was removed and the reaction stirred at room temperature for 1 hour. The reaction was concentrated under vacuum to yield a white solid which was dissolved in H20 and EtOAc, placed in a separatory funnel, and extracted. The organiclayer was washed with 1120, a 10% aqueous solution of HC1, saturated NaHCOa solution, brine, dried with Mg504, filtered through cotton, and concentrated in vacuo to yield 28.26 g (quantitative) of a yellow oil which solidified under vacuumed stirring to a yellow crystalline solid. 1H NMR (400 MHz, CDC13) d 7.90 (d, J = 8.8 Hz, 2H), 7.23 (d, J = 8.3 Hz, 2H), 5.32 (s, 1H),1.15 (s, 9H). 13C NMR (101 MHz, CDC13) d 151.80 (q, J 1.8 Hz), 142.04,129.12, 120.87 (d, J= 1.0 Hz), 120.35 (q, J- 259.1 Hz), 55.01, 30.15. 19F NMR (376 MHz, CDC13) d -57.87.

Reference： [1]Patent: WO2014/145331,2014,A1 .Location in patent: Page/Page column 61
[2]Chemical Communications,2017,vol. 53,p. 5364 - 5367
[3]Chemistry - A European Journal,2018,vol. 24,p. 1241 - 1245
[4]Advanced Synthesis and Catalysis,2018,vol. 360,p. 4625 - 4633

42
[ 22190-35-8 ]
[ 94108-56-2 ]
6-bromo-1-((4-(trifluoromethoxy)phenyl)sulfonyl)-1,2,3,4-tetrahydroquinoline [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 7811 - 7817

43
[ 87691-89-2 ]
[ 94108-56-2 ]
3-(4-(4-(trifluoromethoxy)phenylsulfonyl)piperazin-1-yl)benzo[d]isoxazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	General procedure: To a stirred solution of 3-(piperazin-1-yl)benzo[d]isoxazolederivatives (5a-d) (1.0 equiv.), triethylamine (2.0 equiv.) was added in dichloromethane and cooled to 0oC; to this mixture substituted sulfonylchlorides (1.2 equiv.) were added and allowed to rt, stirred for 1 h. After completion of the reaction, as indicated by TLC, the reaction was quenched with ice cold water and extracted with CH2Cl2. The organic layers were collected, washed with saturated brine solution, dried over anhydrous Na2SO4 and concentrated in vacuo. The resultant crude products were purified by column chromatography [ethyl acetate/hexane (45-80%)] to get the title compounds in yields ranging from 80 to 98%.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 87,p. 71 - 78

44
C₁₁H₁₂ClN₃O [ No CAS ]
[ 94108-56-2 ]
4-chloro-3-(4-(4-(trifluoromethoxy)phenylsulfonyl)piperazin-1-yl)benzo[d]isoxazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	General procedure: To a stirred solution of 3-(piperazin-1-yl)benzo[d]isoxazolederivatives (5a-d) (1.0 equiv.), triethylamine (2.0 equiv.) was added in dichloromethane and cooled to 0oC; to this mixture substituted sulfonylchlorides (1.2 equiv.) were added and allowed to rt, stirred for 1 h. After completion of the reaction, as indicated by TLC, the reaction was quenched with ice cold water and extracted with CH2Cl2. The organic layers were collected, washed with saturated brine solution, dried over anhydrous Na2SO4 and concentrated in vacuo. The resultant crude products were purified by column chromatography [ethyl acetate/hexane (45-80%)] to get the title compounds in yields ranging from 80 to 98%.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 87,p. 71 - 78

45
[ 87757-07-1 ]
[ 94108-56-2 ]
6-chloro-3-(4-(4-(trifluoromethoxy)phenylsulfonyl)piperazin-1-yl)benzo[d]isoxazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	General procedure: To a stirred solution of 3-(piperazin-1-yl)benzo[d]isoxazolederivatives (5a-d) (1.0 equiv.), triethylamine (2.0 equiv.) was added in dichloromethane and cooled to 0oC; to this mixture substituted sulfonylchlorides (1.2 equiv.) were added and allowed to rt, stirred for 1 h. After completion of the reaction, as indicated by TLC, the reaction was quenched with ice cold water and extracted with CH2Cl2. The organic layers were collected, washed with saturated brine solution, dried over anhydrous Na2SO4 and concentrated in vacuo. The resultant crude products were purified by column chromatography [ethyl acetate/hexane (45-80%)] to get the title compounds in yields ranging from 80 to 98%.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 87,p. 71 - 78

46
C₁₁H₁₂ClN₃O [ No CAS ]
[ 94108-56-2 ]
7-chloro-3-(4-(4-(trifluoromethoxy)phenylsulfonyl)piperazin-1-yl)benzo[d]isoxazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	General procedure: To a stirred solution of 3-(piperazin-1-yl)benzo[d]isoxazolederivatives (5a-d) (1.0 equiv.), triethylamine (2.0 equiv.) was added in dichloromethane and cooled to 0oC; to this mixture substituted sulfonylchlorides (1.2 equiv.) were added and allowed to rt, stirred for 1 h. After completion of the reaction, as indicated by TLC, the reaction was quenched with ice cold water and extracted with CH2Cl2. The organic layers were collected, washed with saturated brine solution, dried over anhydrous Na2SO4 and concentrated in vacuo. The resultant crude products were purified by column chromatography [ethyl acetate/hexane (45-80%)] to get the title compounds in yields ranging from 80 to 98%.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 87,p. 71 - 78

47
[ 3964-86-1 ]
[ 94108-56-2 ]
N-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine hydrochloride (0.065 g, 0.225 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with Et3N (65.0 L, 0.473 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (40.0 L, 0.236 mmol). The mixture was warmed to 25 C and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL) and CH2Cl2 (100 mL). The organic layer was washed with saturated aqueous NaCl (3 50 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-15% ethyl acetate-hexanes). The purified fractions were combined, dissolved in a minimal amount of ethyl acetate and precipitated with the addition of hexanes to afford the title compound as a white solid (0.082 g, 76%). 1H NMR (600 MHz, CDCl3) 7.77 (2H, dd, J = 9.0 Hz), 7.23 (2H, d, J = 9.0 Hz), 7.09-7.14 (4H, m), 7.00 (2H, d, J = 7.8 Hz), 6.95 (2H, t, J = 8.4 Hz), 4.75 (1H, t, J = 6.0 Hz), 3.74 (2H, t, J = 6.0 Hz), 3.08 (4H, s), 3.02 (2H q, J = 6.6 Hz), 1.74 (2H, quintet, J = 6.6 Hz); 13C NMR (150 MHz, CDCl3) 152.2, 148.0, 138.4, 134.3, 130.3, 129.3, 123.2, 121.3, 121.1, 119.8, 119.6, 47.5, 41.5, 32.1, 27.5; LCMS m/z 477.2 ([M + H+], C24H23F3N2O3S requires 477.1).

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6528 - 6534

48
4-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)butan-1-amine hydrochloride [ No CAS ]
[ 94108-56-2 ]
N-(4-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)butyl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of 4-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)butan-1-amine hydrochloride (0.0800 g, 0.237 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with triethylamine (68.0 muL, 0.498 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (0.068 g, 0.261 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (100 mL), and CH2Cl2 (100 mL). The organic layer was washed with saturated aqueous NaCl (3 100 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-25% ethyl acetate-hexanes) to afford the title compound as a clear film (0.113 g, 91%). 1H NMR (600 MHz, CDCl3) 7.85 (2H, d, J = 8.8 Hz), 7.30 (2H, d, J = 8.5 Hz), 7.15 (1H, t, J = 7.5 Hz), 7.12 (1H, d, J = 7.5 Hz), 7.02 (1H, d, J = 8.0 Hz), 6.99 (3H, m), 6.87 (1H, dd, J = 8.2, 1.9 Hz), 4.85 (1H, t, J = 6.1 Hz), 3.64 (2H, t, J = 6.2 Hz), 3.09 (4H, m); 2.89 (2H, dd, J = 12.8, 6.5 Hz), 1.52 (4H, m); 13C NMR (150 MHz, CDCl3) 152.2, 149.0, 147.7, 138.4, 135.2, 131.74, 131.67, 131.5, 129.7, 129.3, 126.8, 123.6, 122.4, 121.13, 121.12, 120.6, 119.9, 50.0, 43.1, 32.2, 31.6, 27.2, 24.8; LCMS m/z 525.1 ([M + H+], C25H24ClF3N2O3S requires 525.1).

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6528 - 6534

49
[ 3763-80-2 ]
[ 94108-56-2 ]
N-(3-(2-chloro-10H-phenothiazin-10-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of 3-(2-chloro-10H-phenothiazin-10-yl)propan-1-amine hydrochloride (0.045 g, 0.138 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with Et3N (40.0 L, 0.289 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (24.0 L, 0.144 mmol). The mixture was warmed to 25 C and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL) and CH2Cl2 (100 mL). The organic layer was washed with saturated aqueous NaCl (3 50 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-15% ethyl acetate-hexanes). The purified fractions were combined, dissolved in a minimal amount of ethyl acetate and precipitated with the addition of hexanes to afford the title compound as a white solid (0.068 g, 96%). 1H NMR (600 MHz, CDCl3) 7.70 (2H, dd, J = 9.0 Hz), 7.18-7.22 (4H, m), 7.11 (1H, d, J = 8.4 Hz), 7.02 (1H, d, J = 7.2 Hz), 6.97 (1H, dd, J = 8.4, 1.8 Hz), 6.85 (1H, d, J = 7.8 Hz), 6.82 (1H, dd, J = 1.8 Hz), 5.07 (1H, t, J = 6.0 Hz), 3.93 (2H, t, J = 6.0 Hz), 3.11 (2H q, J = 6.0 Hz), 1.96 (2H, quintet, J = 6.6 Hz); 13C NMR (150 MHz, CDCl3) 152.2, 146.6, 144.6, 138.4, 133.8, 129.3, 128.6, 128.2, 127.9, 126.8, 126.1, 124.9, 121.3, 121.1, 119.8, 116.4, 116.3, 45.3, 41.9, 26.3; LCMS m/z 515.0 ([M + H+], C22H18ClF3N2O3S2 requires 515.0).

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6528 - 6534

50
rac-(1R,2S,6R)-2-amino-6-(5H-dibenzo[b,f]azepin-5-yl)cyclohexanol [ No CAS ]
[ 94108-56-2 ]
rac-N-((1S,2S,3R)-3-(5H-dibenzo[b,f]azepin-5-yl)-2-hydroxycyclohexyl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	[00147] rac-N-((1 S,2S,3R)-3-(5H-dibenzo jb,fj azepin-5-yl)-2-hydroxycyclohexyl)- 4-(trifluoromethoxy)benzenesulfonamide. A solution of rac-( 1R,2S,6R)-2 -amino-6- (5H-dibenzo[bJ]azepin-5-yl)cyclohexanol (0.200 g, 0.653 mmol) in DMF (2.0 mL) was cooled to 0 C, treated with Et3N (90.0 jiL, 0.653 mmol), and 4- trifluoromethoxybenzenesulfonyl chloride (110.0 jiL, 0.653 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaC1 (50 mL), and CH2C12 (100 mL). The organic layer was washed with saturated aqueous NaC1 (3 x 50 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2C12 and purified by flash chromatography (Si02, 0-35% ethyl acetate-hexanes) to afford the title compound Example 25 as a yellow foam (0.322 g, 93%). ?H NMR (600 MHz, CDC13) 7.88 (2H, d, J= 9.0 Hz), 7.18-7.25 (4H, m), 7.07-7.11 (4H, m), 7.04-7.07 (2H, m), 6.75 (2H, s), 5.09 (1H, br s), 3.32 (1H, br s), 3.14-3.20 (1H, br m), 2.95 (1H, t, J= 8.4 Hz), 2.84-2.88 (1H, m), 2.21-2.23 (1H, m), 1.97-2.00 (1H, m), 1.56-1.60 (2H, m), 1.11 (2H, q, J= 12.0 Hz); ?3C NMR (150 MHz, CDC13) 152.1, 149.2, 145.7, 139.0, 137.3, 136.1, 132.8, 132.1, 130.2, 130.1, 130.0, 129.8, 129.5, 128.9, 126.8, 126.1,125.6, 120.9, 119.6, 73.0, 58.3, 31.8, 30.9, 29.3, 22.9; LCMS m/z531.1549 ([M + He], C27H25F3N204S requires 531.1560).

Reference： [1]Patent: WO2015/138496,2015,A1 .Location in patent: Paragraph 00147

51
(1R,2S,6R)-2-amino-6-(3,6-difluoro-9H-carbazol-9-yl)cyclohexanol [ No CAS ]
[ 94108-56-2 ]
N-((1S,2S,3R)-3-(3,6-difluoro-9H-carbazol-9-yl)-2-hydroxycyclohexyl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With triethylamine; In dichloromethane; at 0 - 25℃; for 2h;	A solution of (lR,2S,6R)-2-amino-6-(3,6- difluoro-9H-carbazol-9-yl)cyclohexanol (0.200 g, 0.664 mmol) in (( (2.0 mL) was cooled to 0 C, treated with Et3N (97.0 mu, 0.697 mmol), and 4- trifluoromethoxybenzenesulfonyl chloride (1 18 L, 0.697 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL) and CH2CI2 (100 mL). The organic layer was washed with saturated aqueous NaCl (3 x 50 mL), dried ( a2S04), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2CI2 and purified by flash chromatography (S1O2, 0-35% ethyl acetate-hexanes). The pure fractions were combined, concentrated, and the residue was dissolved in a minimal amount of ethyl acetate and precipitated with the addition of hexanes to afford the title compound Example 32a as a white solid (0.347 g, 97%). [alpha]omicron = +4 (1.0 in CH2CI2). H NMR (600 MHz, CDC13) delta 7.94 (2H, d, J= 8.4 Hz), 7.57 (1H, dd, J = 8.4, 2.4 Hz), 7.48 (1H, dd, J= 9.0, 4.2 Hz), 7.45 (1H, dd, J= 9.0, 2.4 Hz), 7.31 (2H, d, J = 9.0 Hz), 7.11 (1H, td, J= 9.0, 2.4 Hz), 5.93 (1H, d, J = 6.6 Hz), 4.27 (1H, t, J = 9.6, 3.0 Hz), 3.98 (1H, ddd, J= 13.2, 10.2, 4.2 Hz), 3.17-3.23 (1H, m), 3.03 (1H, d, J= 3.0 Hz), 2.22 (1H, qd, J= 13.2, 4.8 Hz), 1.80-1.82 (1H, m), 1.73-1.77 (2H, m), 1.41 (1H, td, J= 12.2, 3.6 Hz), 1.22-1.30 (1H, m); 13C MR (150 MHz, CDC13) delta 157.9 (d, J = 24 Hz), 156.3 (d, J= 18 Hz), 152.3, 139.7, 138.7, 135.4, 129.2, 124.3 (dd, J= 36, 18 Hz), 122.5 (dd, J= 36, 18 Hz), 121.1, 120.4 (q, J= 1032 Hz), 1 14.4 (d, J= 102 Hz), 1 13.9 (d, J= 36 Hz), 112.3 (d, J= 36 Hz), 1 10.1 (d, J= 36 Hz), 106.4 (d, J= 96 Hz), 105.8 (d, J= 96 Hz), 72.4, 60.1, 59.1, 31.4, 28.3, 22.7; LCMS m/z 541.1223 ([M + H+], C25H21F5N2O4S requires 541.1215).

Reference： [1]Patent: WO2015/138500,2015,A1 .Location in patent: Paragraph 00225

52
(1R,2S,6R)-2-amino-6-(9H-carbazol-9-yl)cyclohexanol [ No CAS ]
[ 94108-56-2 ]
(1S,2S,3R)-N-(3-(9H-carbazol-9-yl)-2-hydroxycyclohexyl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of rac-(1S,2S,6R)-2-amino-6-(9H- carbazol-9-yl)cyclohexanol (7.11 g, 25.4 mmol) in DMF (50.0 mL) was cooled to 0 C, treated with Ets (3.52 mL, 25.4 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (4.30 mL, 25.4 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (200 mL), and CH2CI2 (300 mL). The aqueous layer was extracted with CH2CI2 (3 x 200 mL). The combined organic layers were washed with saturated aqueous NaCl (4 x 200 mL), dried ( a2S04), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2CI2 and purified by flash chromatography (S1O2, 0-25% ethyl acetate-hexanes). The purified fractions were combined, dissolved in a minimal amount of ethyl acetate, and were precipitated with the addition of hexanes to afford the title compound as a white solid (11.9 g, 88%). 'H NMR (600 MHz, CDCI3) delta (as a mixture of rotamers) 2H[8.1 1 (d, J= 7.2 Hz), 8.06 (d, J= 7.8 Hz)], 2H[7.93 (d, J= 9.0 Hz), 7.86 (d, J= 9.0 Hz)], 7.52 (1H, d, J= 7.8 Hz)], 7.38-7.45 (2H, m), 7.36 (1H, d, J= 8.4 Hz), 7.30 (1H, d, J= 8.4 Hz), 7.22-7.27 (3H, m), 5.76 (1H, t, J = 10.2 Hz), 1H[5.19 (d, J= 4.8 Hz), 5.09 (d, J= 8.4 Hz)], 2H[4.56 (td, J= 12.0, 4.2 Hz), 4.29-4.38 (m)], 1Eta[3.60-3.66 (m), 3.23-3.27 (m)], 1H[2.49 (qd, J= 13.2, 3.6 Hz), 2.41 (qd, J= 1 1.1, 1.8 Hz)], lH[2.24-2.25 (m), 2.19 (m)], 2H[1.97 (t, J= 15.0 Hz), 1.90 (d, J= 10.8 Hz)], 2H[1.59-1.66 (m), 1.47-1.55 (m)]; LCMS m/z 505.1415 ([M + H+], C25H23F3N2O4S requires 505.1403).

Reference： [1]Patent: WO2015/138500,2015,A1 .Location in patent: Paragraph 00178

53
[ 2243-61-0 ]
[ 94108-56-2 ]
N,N'-(naphthalene-1,4-diyl)bis(4-(trifluoromethoxy)benzenesulfonamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With pyridine In toluene at 100℃; for 2h;

Reference： [1]Jiang, Zheng-Yu; Xu, Li-Li; Lu, Meng-Chen; Chen, Zhi-Yun; Yuan, Zhen-Wei; Xu, Xiao-Li; Guo, Xiao-Ke; Zhang, Xiao-Jin; Sun, Hao-Peng; You, Qi-Dong [Journal of Medicinal Chemistry, 2015, vol. 58, # 16, p. 6410 - 6421]

54
[ 94108-56-2 ]
[ 535170-20-8 ]
C₁₈H₁₇F₅N₂O₅S [ No CAS ]

Reference： [1]Bulletin of the Korean Chemical Society,2016,vol. 37,p. 1632 - 1637

55
6-(3-aminopropyl)-6H-dibenzo[b,f][1,4,5]oxathiazepine-5,5-dioxide [ No CAS ]
[ 94108-56-2 ]
N-(3-(5,5-dioxido-6H-dibenzo[b,f][1,4,5]oxathiazepin-6-yl)propyl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine; In dichloromethane; at 0 - 25℃; for 2h;	A solution of 6-(3 -aminopropyl)6H-dibenzo[b,fj[1,4,5]oxathiazepine 5,5-dioxide (0.072 g, 0.238 mmol) in CH2C12 (1.5 mL) was cooled to 0 C, treated with Et3N (36.3 jiL, 0.262 mmol), and 4- trifluoromethoxybenzenesulfonyl chloride (44.4 jiL, 0.262 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaC1 (50 mL) and CH2C12 (50 mL). The organic layer was washed with saturated aqueous NaC1 (20 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2C12 and purified by flash chromatography (Si02, 0- 35% ethyl acetate-hexanes) to afford Example 12 (0.109 g, 86%). ?HNIVIR (600 IVIFIz, CDC13) oe 7.93 (2H, br s), 7.84 (1H, br s), 7.54 (1H, br s), 7.40 (1H, br s), 7.30-7.34 (4H, m), 7.27 (2H, br s), 5.23 (1H, s), 3.71 (2H, s), 3.25 (2H, s), 1.81 (2H, s); ?3C NIVIR (150 IVIHz, CDC13) oe 155.9, 152.3, 145.5, 138.7, 134.3, 131.9, 131.3, 131.0, 130.7, 129.4, 129.1, 126.9, 124.9, 123.0, 122.8, 122.4, 121.3, 48.7, 39.9, 29.1; LCMS m/z 529.0771 ([M + Hj, C22H,9F3N206S2 requires 529.0709).

Reference： [1]Patent: WO2017/44571,2017,A1 .Location in patent: Paragraph 00218

56
6-(3-amino-2-hydroxycyclohexyl)-6H-dibenzo[b,f][1,4,5]oxathiazepine-5,5-dioxide [ No CAS ]
[ 94108-56-2 ]
N-((1R,2S,3S)-3-(5,5-dioxido-6H-dibenzo[b,f][1,4,5]oxathiazepin-6-yl)-2-hydroxycyclohexyl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With triethylamine; In dichloromethane; at 0 - 25℃; for 2h;	A solution of 6-((1 R,2R, 3 S)-3 -amino-2-hydroxycyclohexyl)-6H-dibenzo [b, f] [1,4,5 ]oxathiazepine 5,5 -dioxide (0.0500 g, 0.139 mmol) in CH2C12 (1.0 mL) was cooled to 0 C, treated with Et3N (20.2 jiL, 0.146 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (24.7 jiL, 0.146 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaC1 (50 mL) and CH2C12 (100 mL). The organic layer was washed with saturated aqueous NaC1 (3 x 50 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2C12 and purified by flash chromatography (Si02, 0-35% ethyl acetate-hexanes) to afford the title compound as a beige film (0.0738 g, 91%). ?H NIVIR (600 IVIFIz, CDC13) oe 7.94 (2H, d, J= 6.6 Hz), 7.81 (1H, dd, J= 7.8, 1.8 Hz), 7.49 (1H, td, J= 7.8, 1.2 Hz), 7.40 (1H, td, J 7.8, 1.2 Hz), 7.28- 7.31 (4H, m), 7.26 (1H, td, J 7.8, 1.2 Hz), 7.22 (1H, td, J= 8.4, 1.2 Hz), 5.42 (1H, d, J=4.8 Hz), 4.01 (1H, ddd, J 12.0, 10.2, 4.2 Hz), 3.30 (1H, t, J= 9.0 Hz), 3.23 (1H, br s),3.00-3.05 (1H, m), 1.91-1.98 (2H, m), 1.58-1.61 (1H, m), 1.26-1.30 (2H, m), 1.09 (1H, qd, J 13.2, 3.6 Hz); ?3C NIVIR (600 IVIHz, CDC13) oe 156.5, 152.3, 152.2, 138.7, 133.9, 133.0, 132.4, 131.1, 129.5, 128.2, 127.5, 127.0, 124.4, 122.7, 122.0, 121.2, 121.0, 73.7, 65.1, 58.9,31.1, 28.9, 22.1; LCMS m/z 585.0980 ([M + Hj, C25H23F3N207S2 requires 585.0972).

Reference： [1]Patent: WO2017/44571,2017,A1 .Location in patent: Paragraph 00170; 00176

57
rac-(1R,2S,6R)-2-amino-6-(dibenzylamino)cyclohexanol [ No CAS ]
[ 94108-56-2 ]
rac-N-((1S,2S,3R)-3-(dibenzylamino)-2-hydroxycyclohexyl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of rac-(lR,2S,6R)-2-amino-6- (dibenzylamino)cyclohexanol (0.200 g, 0.644 mmol) in DMF (2.0 mL) was cooled to 0 C, treated with Et N (89.0 L, 0.644 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (109.0 L, 0.644 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2CI2 (100 mL). The organic layer was washed with saturated aqueous NaCl (3 x 50 mL), dried (Na2SC"4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2CI2 and purified by flash chromatography (S1O2, 0-35% ethyl acetate-hexanes) to afford the title compound as a yellow solid (0.322 g, 93%). NMR (600 MHz, CDC13) delta 7.83 (2H, d, J = 9.0 Hz), 7.16-7.24 (8H, m), 7.12 (4H, d, J= 7.12 Hz), 4.90 (1H, d, J= 3.6 Hz), 3.71 (2H, d, J= 13.2 Hz), 3.56 (1H, br s), 3.27 (2H, d, J= 13.8 Hz), 3.17 (1H, t, J= 9.6 Hz), 2.69-2.74 (1H, m), 2.26 (1H, m), 2.04-2.06 (1H, m), 1.81-1.84 (1H, m), 1.69 (1H, doublet of quintets, J= 10.8, 3.0 Hz), 1.10-1.22 (2H, m), 1.01-1.09 (1H, m); 1 C NMR (150 MHz, CDC13) delta 152.1, 139.1, 139.0, 129.6, 129.0, 128.8, 127.6, 120.9, 119.6, 71.8, 62.5, 59.0, 53.8, 31.7, 22.5, 21.8; LCMS m/z 535.1863 ([M + H+], C27H29F3N2O4S requires 535.1873).

Reference： [1]Patent: WO2017/44572,2017,A1 .Location in patent: Paragraph 00202

58
rac-(1R,2S,6R)-2-amino-6-(bis(4-(trifluoromethyl)phenyl)amino)cyclohexanol [ No CAS ]
[ 94108-56-2 ]
rac-N-((1S,2S,3R)-3-(bis(4-(trifluoromethyl)phenyl)amino)-2-hydroxycyclohexyl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With triethylamine; In dichloromethane; at 0 - 25℃; for 2h;	A solution of (lR,2,S',6R)-2-amino-6-(bis(4-(trifluoromethyl)phenyl)amino)cyclohexanol (0.075 g, 0.179 mmol) in CH2CI2 (2.0 mL) was cooled to 0 C, treated with Et3N (27.3 mu, 0.197 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (33.4 L, 0.197 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL) and CH2CI2 (100 mL). The organic layer was washed with saturated aqueous NaCl (3 x 50 mL), dried (Na2S04), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2CI2 and purified by flash chromatography (S1O2, 0- 35% ethyl acetate-hexanes) to afford the title compound as a white solid (0.110 g, 96%). mp. 97-98 C, (white powder, ethyl acetate-hexanes); NMR (600 MHz, CDCI3) delta 7.96 (2H, d, J= 9.0 Hz), 7.53 (4H, d, J= 8.4 Hz), 7.35 (2H, d, J= 9.0 Hz), 6.99 (4H, d, J= 7.8 Hz), 4.92 (1H, d, J= 6.6 Hz), 3.94 (1H, ddd, J= 13.2, 9.6, 4.2 Hz), 3.18-3.21 (lH, m), 3.17 (1H, t, J= 9.6 Hz), 2.89 (1H, br s), 1.97-1.99 (1H, m), 1.81-1.84 (1H, m), 1.72 (lH, doublet of quintets, J= 14.4, 3.0 Hz), 1.37 (1H, qt, J= 13.2, 3.0 Hz), 1.22 (1H, qd, J= 13.2, 3.6 Hz), 1.07 (1H qd, J= 13.2, 4.2 Hz); LCMS m/z 643.1304 ([M + H+], C27H23F9N2O4S requires 643.1308).

Reference： [1]Patent: WO2017/44572,2017,A1 .Location in patent: Paragraph 00170; 00176

59
rel-(1R,2S,6R)-2-amino-6-(dibenzylamino)cyclohexanol [ No CAS ]
[ 94108-56-2 ]
N-(rel-(1S,2S,3R)-3-(dibenzylamino)-2-hydroxycyclohexyl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h;	A solution of re/-(lR,2S,6R)-2-amino-6- (dibenzylamino)cyclohexanol (0.200 g, 0.644 mmol) in DMF (2.0 mL) was cooled to 0 C, treated with Et N (89.0 L, 0.644 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (109.0 L, 0.644 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL), and CH2CI2 (100 mL). The organic layer was washed with saturated aqueous NaCl (3 x 50 mL), dried (Na2S04), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2CI2 and purified by flash chromatography (S1O2, 0-35% ethyl acetate-hexanes) to afford the title compound as a yellow solid (0.322 g, 93%). NMR (600 MHz, CDC13) delta 7.83 (2H, d, J = 9.0 Hz), 7.16-7.24 (8H, m), 7.12 (4H, d, J= 7.12 Hz), 4.90 (1H, d, J= 3.6 Hz), 3.71 (2H, d, J= 13.2 Hz), 3.56 (1H, br s), 3.27 (2H, d, J= 13.8 Hz), 3.17 (1H, t, J= 9.6 Hz), 2.69-2.74 (1H, m), 2.26 (1H, m), 2.04-2.06 (1H, m), 1.81-1.84 (1H, m), 1.69 (1H, doublet of quintets, J= 10.8, 3.0 Hz), 1.10-1.22 (2H, m), 1.01-1.09 (1H, m); 1 C NMR (150 MHz, CDCI3) delta 152.1, 139.1, 139.0, 129.6, 129.0, 128.8, 127.6, 120.9, 119.6, 71.8, 62.5, 59.0, 53.8, 31.7, 22.5, 21.8; LCMS m/z 535.1863 ([M + H+], C27H29F3N2O4S requires 535.1873).

Reference： [1]Patent: WO2017/44575,2017,A1 .Location in patent: Paragraph 00155

60
(R)-1-benzhydrylpiperidin-3-amine [ No CAS ]
[ 94108-56-2 ]
(R)-N-(1-benzhydrylpiperidin-3-yl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With triethylamine; In dichloromethane; at 25℃; for 2h;	A solution of (R)-l-benzhydrylpiperidin-3- amine (0.100 g, 0.375 mmol) in CH2CI2 (1.0 mL) was cooled to 0 C, treated with Et3N (52.0 L, 0.375 mmol), and 4-trifluoromethoxybenzenesulfonyl chloride (52.0 L, 0.375 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (50 mL) and CH2CI2 (100 mL). The organic layer was washed with saturated aqueous NaCl (50 mL), dried (Na2S04), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2CI2 and purified by flash chromatography (S1O2, 0-20% ethyl acetate-hexanes) to afford the title compound as a white solid (0.170 g, 92%). [a]D = +48 (CH2CI2, c = 1.0); mp. 161-162 C, (white powder, ethyl acetate-hexanes). [00188] Other examples of formula I may be made as shown below:

Reference： [1]Patent: WO2017/44575,2017,A1 .Location in patent: Paragraph 00187

61
[ 186393-31-7 ]
[ 94108-56-2 ]
(3R,4R)-1-(4-(trifluoromethoxy)phenylsulfonyl)pyrrolidine-3,4-diol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: (3R,4R)-pyrrolidine-3,4-diol With pyridine In tetrahydrofuran for 0.0833333h; Stage #2: 4-(trifluoro-methoxy)benzene-1-sulfonyl chloride In tetrahydrofuran at 20℃; for 16h; Inert atmosphere;	General procedure for the preparation of compounds 8/9(a-c) and 12/13(a-c) General procedure: Pyridine (5 mol) was added to a stirred solution of corresponding amine (1.0 mol) in THF (10 v), after 5 minutes, sulfonyl chloride derivative (1.1 mol) was added, stirred at room temperature under argon atmosphere for 16 h. Then the reaction mixture was diluted with water (50 v), extracted with EtOAc (50 v X 2), evaporated the solvent in vacuo, the crude product was purified by column chromatography to afford 8/9(a-c) and 12/13(a-b) (58-86%) as solids. During thesynthesis of N-(4-(3-((3S,4S)-3,4-Dihydroxypyrrolidin-1-yl)-3-oxopropyl)phenyl)-4-(trifluoromethyl)benzenesulfonamide (13b), isolated 29% of disulphonation product N-(4-(3 N-(4-(3-((3S,4S)-3,4-Dihydroxypyrrolidin-1-yl)-3-oxopropyl)phenyl)-4-(trifluoromethyl)-N-(4-(trifluoromethyl)phenylsulfonyl)benzenesulfonamide (13c) as white solid.

Reference： [1]Kasturi, Sivaprasad; Surarapu, Sujatha; Uppalanchi, Srinivas; Anireddy, Jaya Shree; Dwivedi, Shubham; Anantaraju, Hasitha Shilpa; Perumal, Yogeeswari; Sigalapalli, Dilep Kumar; Babu, Bathini Nagendra; Ethiraj, Krishna S. [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 12, p. 2818 - 2823]

62
[ 90481-32-6 ]
[ 94108-56-2 ]
(3S,4S)-1-(4-(trifluoromethoxy)phenylsulfonyl)pyrrolidine-3,4-diol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%		General procedure: Pyridine (5 mol) was added to a stirred solution of corresponding amine (1.0 mol) in THF (10 v), after 5 minutes, sulfonyl chloride derivative (1.1 mol) was added, stirred at room temperature under argon atmosphere for 16 h. Then the reaction mixture was diluted with water (50 v), extracted with EtOAc (50 v X 2), evaporated the solvent in vacuo, the crude product was purified by column chromatography to afford 8/9(a-c) and 12/13(a-b) (58-86%) as solids. During thesynthesis of N-(4-(3-((3S,4S)-3,4-Dihydroxypyrrolidin-1-yl)-3-oxopropyl)phenyl)-4-(trifluoromethyl)benzenesulfonamide (13b), isolated 29% of disulphonation product N-(4-(3 N-(4-(3-((3S,4S)-3,4-Dihydroxypyrrolidin-1-yl)-3-oxopropyl)phenyl)-4-(trifluoromethyl)-N-(4-(trifluoromethyl)phenylsulfonyl)benzenesulfonamide (13c) as white solid.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2818 - 2823

63
2-methyl-4-carbonyl-4,6,7,8-tetrahydropyrrolo[1,2-a]thiophene[2,3-d]pyrimidin-3-amine hydrochloride [ No CAS ]
[ 94108-56-2 ]
4-trifluoromethoxy-N-(2-methyl-4-carbonyl-4,6,7,8-tetrahydropyrrolo[1,2-a]thiophene[2,3-d]pyrimidin-3-amino)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With triethylamine; In dichloromethane; at 20℃;	General procedure: at room temperature,2-methyl-4-carbonyl-4,6,7,8-tetrahydropyrrole [1,2-a] thiophene [2,3-d] pyrimidin-Hydrochloride Compound 9 (0.29 g, 1 mmol) was dissolved in anhydrous dichloromethane (10 ml)Followed by the addition of 4-trifluoromethoxybenzenesulfonyl chloride (0.29 g, 1.1 mmol)Triethylamine (0.12 g, 1.2 mmol) was slowly added with stirring, stirred at room temperature overnight,Reaction to the material completely disappeared, dichloromethane extraction, concentration,Using a 2: 1 by volume petroleum ether: ethyl acetate column chromatography elution, that was compound 9g;Yield: 88%, pale yellow solid

Reference： [1]Patent: CN106749315,2017,A .Location in patent: Paragraph 0150; 0151; 0152

64
C₁₁H₁₃N₃OS*ClH [ No CAS ]
[ 94108-56-2 ]
4-trifluoromethoxy-N-(2-methyl-4-carbonyl-4,6,7,8-tetrahydropyrido[1,2-a]thiophene[2,3-d]pyrimidin-3-amino)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine; In dichloromethane; at 20℃;	at room temperature,2-methyl-4-carbonyl-6,7,8,9-tetrahydropyrido [1,2-a] thiophene [2,3-d] pyrimidin-3-amine hydrochloride Compound 10 (0.31 g, 1 mmol) was dissolved in anhydrous dichloromethane (10 ml)Followed by the addition of 4-trifluoromethoxybenzenesulfonyl chloride (0.29 g, 1.1 mmol)Triethylamine (0.12 g, 1.2 mmol) was slowly added with stirring, stirred at room temperature overnight,Reaction to the material completely disappeared, dichloromethane extraction, concentration,Using a 5: 1 by volume petroleum ether: ethyl acetate column chromatography gradient elution,To give compound 10e; yield: 86% as a pale yellow solid

Reference： [1]Patent: CN106749315,2017,A .Location in patent: Paragraph 0168; 0169; 0170

65
2-methyl-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]thieno[2,3-d]pyrimidin-3-amine hydrochloride [ No CAS ]
[ 94108-56-2 ]
4-trifluoromethoxy-N-(2-methyl-4-carbonyl-4,6,7,8-tetrahydropyrrolo[1,2-a]thiophene[2,3-d]pyrimidin-3-amino)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With triethylamine; In dichloromethane; at 20℃;	At room temperature,2-methyl-4-carbonyl-4,6,7,8-tetrahydropyrrole [1,2-a] thiophene [2,3-d] pyrimidin-3-amine hydrochlorideCompound 9 (0.29 g, 1 mmol) was dissolved in anhydrous dichloromethane (10 ml)Followed by the addition of 4-trifluoromethoxybenzenesulfonyl chloride (0.29 g, 1.1 mmol)Triethylamine (0.12 g, 1.2 mmol) was slowly added with stirring, stirred at room temperature overnight,Reaction to the raw material completely disappeared, dichloromethane extraction, concentration, the use of 2: 1 by volume of petroleum ether:Ethyl acetate column chromatography to give 9 g of compound; Yield: 88%, pale yellow solid

Reference： [1]Patent: CN106749317,2017,A .Location in patent: Paragraph 0150

66
3-amino-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]thieno[2,3-d]pyrimidin-4-one dihydrochloride [ No CAS ]
[ 94108-56-2 ]
4-trifluoromethoxy-N-(2-methyl-4-carbonyl-4,6,7,8-tetrahydropyrido[1,2-a]thiophene[2,3-d]pyrimidin-3-amino)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine; In dichloromethane; at 20℃;	At room temperature,2-methyl-4-carbonyl-6,7,8,9-tetrahydropyrido [1,2-a] thiophene [2,3-d] pyrimidin-3-amine hydrochlorideCompound 10 (0.31 g, 1 mmol) was dissolved in anhydrous dichloromethane (10 ml)Followed by the addition of 4-trifluoromethoxybenzenesulfonyl chloride (0.29 g, 1.1 mmol)Triethylamine (0.12 g, 1.2 mmol) was slowly added with stirring, stirred at room temperature overnight,Reaction to the complete disappearance of raw materials, extraction and concentration of dichloromethane, the use of volume ratio of 5: 1 petroleum ether:Ethyl acetate column chromatography to give compound 10e; yield: 86%, pale yellow solid
	With pyridine; In dichloromethane; at 20℃; for 12h;	General procedure: To a mixture of 3-amino-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]thieno[2,3-d]pyrimidin-4-one (1.0 mmol) (10) and pyridine (1.2 mmol) in CH2Cl2 (2 mL),benzenesulfonyl chloride (1.1 mmol) in CH2Cl2 (10 mL) was added dropwise. There sulting mixture was stirred at room temperature for 12 h. The mixture was concentrated under reduced pressure, and the residue was diluted with water(30 mL). The aqueous mixture was neutralized by the addition of aqueous 10% HCl solution and extracted with CH2Cl2 (2 9 30 mL). The organic phase was washed with aqueous saturated NH4Cl solution and brine. The organic layer was separated and dried over anhydrous MgSO4, filtered, and concentrated under reduced pressureto give the crude product, which was purified by silica gel chromatography to produce the pure corresponding compounds. The full structual elucidation of compounds 11a-11x can be found in the electronic supplementary material associated with this article

Reference： [1]Patent: CN106749317,2017,A .Location in patent: Paragraph 0168; 0169; 0170
[2]Research on Chemical Intermediates,2017,vol. 43,p. 6835 - 6843

67
[ 38385-95-4 ]
[ 94108-56-2 ]
2-(1-((4-(trifluoromethoxy)phenyl)sulfonyl)piperidin-4-yl)-1H-benzo[d]imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With triethylamine; In dichloromethane; at 20℃;Inert atmosphere;	In a round bottomed flask equipped with a nitrogen inlet and a magnetic stir bar, 4- trifluoromethoxybenzenesulfonyl chloride (313 mg, 1.2 mmol), 2-(piperidin-4-yl)-lH- benzo[d]imidazole (200 mg, 1 mmol) and Epsilon Nu (0.28 mL, 2 mmol) in CH2CI2 (5 mL) was added. The mixture was then stirred at room temperature for overnight. The precipitate was then filtered, washed with CH2CI2 and the residue was dried in vacuo yielding 304 mg (71 %) of 2- (l-((4-(trifluoromethoxy)phenyl)sulfonyl)piperidin-4-yl)-lH-benzo[d]imidazole. (0410) 'H NMR (400 MHz, DMSO-d6) delta 12.16 (s, 1H), 7.89 (d, J = 8.9 Hz, 2H), 7.62 (d, J = 8.9 Hz, 2H), 7.47 (d, J= 8.4 Hz, 1H), 7.36 (d, J= 8.4 Hz, 1H), 7.11-7.03 (m, 2H), 3.67 (d, J = 11.8 Hz, 2H), 2.93-2.83 (m, 1H), 2.54-2.48 (m, 2H), 2.13-2.03 (m, 2H), 1.88-1.74 (m, 2H). (0411) 1 C NMR (101 MHz, DMSO-d6) delta 157.15 , 151.72 , 143.25 , 135.00 , 134.63 , 130.54 , 122.02, 121.97, 121.31 , 118.72 , 111.26 , 45.95 , 34.70 , 29.93. (0412) HRMS: MH+ = 426.10960 (Theoretically = 426.10937)

Reference： [1]Patent: WO2018/144900,2018,A1 .Location in patent: Page/Page column 61

68
3-amino-2-methyl-7,8-dihydropyrrolo[1,2-a]thieno[2,3-d]pyrimidin-4(6H)-one [ No CAS ]
[ 94108-56-2 ]
4-trifluoromethoxy-N-(2-methyl-4-carbonyl-4,6,7,8-tetrahydropyrrolo[1,2-a]thiophene[2,3-d]pyrimidin-3-amino)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With pyridine; In dichloromethane; at 20℃; for 12h;	General procedure: To a mixture of 3-amino-2-methyl-thieno[2,3-d]pyrimidin-4(6H)-one (1.0 mmol) (8 and 9) and benzenesulfonyl chloride (1.1 mmol) in DCM (10 mL) was added dropwise pyridine (1.2 mmol) in dichloromethane (2 mL). The resulting mixture was stirred at room temperature for 12 hrs. The mixture was concentrated under reduced pressure, and theresidue was treated with water (30 mL). The aqueous mixture was neutralized by the addition of aqueous 10% HCl solution and extracted with DCM (230 mL). The organicphase was washed with aqueous saturated NH4Cl solution and brine. The organic layer was separated and dried over anhydrous MgSO4, filtered, and concentrated under reducedpressure to give the crude product, which was purified by silica gel chromatography to produce the pure corresponding compounds.

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2018,vol. 193,p. 656 - 667

69
3-amino-2-methyl-7,8-dihydropyrrolo[1,2-a]thieno[2,3-d]pyrimidin-4(6H)-one [ No CAS ]
[ 94108-56-2 ]
N-(2-methyl-4-oxo-4,6,7,8,9,10-hexahydrothieno[2’,3’:4,5]pyrimido[1,2-a]azepin-3-yl)-4-(trifluoromethoxy)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With pyridine; In dichloromethane; at 20℃; for 12h;	General procedure: To a mixture of 3-amino-2-methyl-thieno[2,3-d]pyrimidin-4(6H)-one (1.0 mmol) (8 and 9) and benzenesulfonyl chloride (1.1 mmol) in DCM (10 mL) was added dropwise pyridine (1.2 mmol) in dichloromethane (2 mL). The resulting mixture was stirred at room temperature for 12 hrs. The mixture was concentrated under reduced pressure, and theresidue was treated with water (30 mL). The aqueous mixture was neutralized by the addition of aqueous 10% HCl solution and extracted with DCM (230 mL). The organicphase was washed with aqueous saturated NH4Cl solution and brine. The organic layer was separated and dried over anhydrous MgSO4, filtered, and concentrated under reducedpressure to give the crude product, which was purified by silica gel chromatography to produce the pure corresponding compounds.

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2018,vol. 193,p. 656 - 667

70
C₂₉H₃₇N₅O₃ [ No CAS ]
[ 94108-56-2 ]
C₃₆H₄₀F₃N₅O₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium carbonate; In dichloromethane; at 20℃;	General procedure: To a stirred solution of compound 6(101mg, 0.2mmol) and K2CO3 (69mg, 0.5mmol) in dry DCM (5mL), acyl chloride or sulfonyl chloride(0.3mmol) was added and stirred for 2-12h at rt. After completion of the reaction as indicated by TLC,the reaction was quenched by the addition of saturated NaHCO3 (10mL) and extracted with CH2Cl2(3×5mL). The organic layer was dried using anhydrous Na2SO4, concentrated in vacuo and purified bycolumn chromatography (2% CH3OH/DCM) to afford products.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29,p. 806 - 810

71
[ 81-64-1 ]
[ 94108-56-2 ]
1,4-bis(4-trifluoromethoxybenzenesulfonato)-9,10-anthraquinone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With potassium carbonate In acetone at 60℃;	1.4; 2.4; 3.4 (4) Preparation of 1,4-bis(4-trifluoromethoxybenzenesulfonate)-9,10-anthraquinone (C04): It was added 1,4-dihydroxy anthraquinone 0.5g (2mmol) in a glass flask,Excess 4-trifluoromethoxybenzenesulfonyl chloride 1.5g,Anhydrous potassium carbonate 0.5g, then added 20mL of anhydrous acetone,The reaction is refluxed in an oil bath at 60 ° C,TLC monitors the response throughout the process,After the reaction,Add appropriate amount of ice water to quench the reaction.Filtered to light yellow crude product,Purified by silica gel column chromatography.Eluent: (dichloromethane: petroleum ether = 1:2) afforded pale yellow title compound (yield: 79%).

Reference： [1]Current Patent Assignee: GUANGXI UNIVERSITY - CN109608369, 2019, A Location in patent: Paragraph 0041; 0048-0049; 0074; 0081-0082; 0107; 0114-0115

72
[ 116797-02-5 ]
[ 94108-56-2 ]
4-methyl-1'-((4-(trifluoromethoxy)phenyl)sulfonyl)-1,4'-bipiperidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;

Reference： [1]Wang, Wentian; Zhang, Lu; Morlock, Lorraine; Williams, Noelle S.; Shay, Jerry W.; De Brabander, Jef K. [Journal of Medicinal Chemistry, 2019, vol. 62, # 10, p. 5217 - 5241]

73
[ 931-53-3 ]
[ 94108-56-2 ]
S-4-(trifluoromethoxy)phenyl cyclohexylcarbamothioate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium iodide; In water; N,N-dimethyl-formamide; at 50℃; for 4h;	General procedure: Cyclohexyl isocyanide 1 (0.1 mmol), sulfonyl chloride 2 (0.25 mmol), KI (0.15 mmol), and DMF/H2O (50:1, 1.5 mL) were successively added to a round-bottom flask, and the mixture was then heated at 50 C for 4 h. All the reactions were monitored by TLC. After completion, the reaction system was cooled to room temperature, saturated Na2S2O3 solution (15 mL) was added, and the reaction mixture was extracted with EtOAc (10 mL × 3). The organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to obtain the crude product. The S-Thiocarbamates 3 were purified by column chromatography on silica gel.

Reference： [1]Journal of Chemical Research,2019,vol. 43,p. 347 - 351

74
[ 61500-87-6 ]
[ 94108-56-2 ]
C₁₆H₁₁F₆NO₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; In dichloromethane; at 20℃; for 36h;	General procedure: To a solution of methyl 2-amino-4-fluorobenzoate (1.64 g, 9.71 mmol) and methanesulfonyl chloride (5.28 mL, 115 mmol) in dichloromethane (100 mL) was added pyridine (7.86 mL, 97.1 mmol). The solution was stirred at room temperature for 18 hours. The reaction was quenched with 1N HCl and was stirred for 5 minutes. The mixture was extracted with DCM (3×). The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered and concentrated. The crude product was purified by silica gel chromatography to afford methyl 4-fluoro-2-(methylsulfonamido)benzoate.

Reference： [1]Patent: US2019/359565,2019,A1 .Location in patent: Paragraph 0347; 0355

75
[ 1477-55-0 ]
[ 94108-56-2 ]
N,N'-(1,3-phenylenebis(methylene))bis(2-chlorobenzenesulfonamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.1%	With triethylamine; In dichloromethane; at 0 - 20℃; for 2h;	General procedure: A solution of 1,3-Bis(aminomethyl)benzene (100 mg, 0.73 mmol) and 0.25 ml triethylamine in 20 ml dichloromethane was stirred at 0 C. To this solution was slowly added appropriate benzamide or benzenesulfonamide (2.2 mmol) in 20 ml dichloromethane dropwise. After 10 minutes, the reaction mixture was then placed to ambient temperature and stirred for 2 hours. Upon completion, the reaction mixture was concentrated under reduced pressure. Purification by flash chromatography (silica gel, dichloromethane/methanol 40: 1) afforded a white solid.

Reference： [1]Chinese Chemical Letters,2020

76
[ 616-38-6 ]
[ 94108-56-2 ]
[ 2546-45-4 ]

Yield	Reaction Conditions	Operation in experiment
62%	With tin; water; potassium hydrogencarbonate; triphenylphosphine; sodium iodide at 120℃; for 48h; Sealed tube;

Reference： [1]Miao, Ren-Guan; Qi, Xinxin; Wu, Xiao-Feng [European Journal of Organic Chemistry, 2021, vol. 2021, # 37, p. 5219 - 5221]

77
[ 1152568-45-0 ]
[ 94108-56-2 ]
[ 2819659-04-4 ]

Yield	Reaction Conditions	Operation in experiment
79%	With triethylamine In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran at 20℃; Sealed tube;	139.3 Step 3: Synthesis of 4-(trifluoromethoxy)-N-((1-(3- (trifluoromethyl)phenyl)cyclopentyl)methyl)benzenesulfonamide (262) In a sealed vial, 4-(trifluoromethoxy)benzenesulfonyl chloride (0.070 mL, 0.415 mmol) was added to a stirred solution of [ 1 -[3- (trifluoromethyl)phenyl]cyclopentyl]methanamine (101 mg, 0.415 mmol) and triethylamine (0.23 mL, 1.66 mmol) in DCM (2.7678 mL). The solution was stirred at rt 2.5 h then DCM and an halfsaturated solutionof NaHCO3were added and the aqueous layer was extracted twice with DCM. The combined organic layers were filtered through phase separator, then concentrated in vacuo, and purified by flash chromatography on silica gel using a gradient of EtOAc in Heptane from 5% to 25% to afford the title compound as a colorless oil (153.2 mg, 99.8% purity, 79% yield, ti = 3.08 min). LCMS (Method C): m/z found 466.2 [M-H]';1H- NMR (DMSO-d6, 500 MHz) δ ( ppm) 7.78 (d, J = 8.8 Hz, 2H), 7.61 - 7.43 (m, 7H), 2.95 - 2.90 (m, 2H), 2.14 - 1.72 (m, 4H), 1.70 - 1.52 (m, 4H).

Reference： [1]Current Patent Assignee: RAPPTA THERAPEUTICS - WO2022/167866, 2022, A1 Location in patent: Page/Page column 317-319

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	94108-56-2	MDL No. :	MFCD00042408
Formula :	C₇H₄ClF₃O₃S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UHCDBMIOLNKDHG-UHFFFAOYSA-N
M.W :	260.62	Pubchem ID :	523102
Synonyms :

Num. heavy atoms :	15
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	3
Num. H-bond acceptors :	6.0
Num. H-bond donors :	0.0
Molar Refractivity :	46.21
TPSA :	51.75 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.67 cm/s

[ CAS No. 94108-56-2 ] {[proInfo.proName]}

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Water Solubility

Medicinal Chemistry

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Application In Synthesis of [ 94108-56-2 ]

[ 94108-56-2 ] Synthesis Path-Downstream 1~77

Related Functional Groups of
[ 94108-56-2 ]

Fluorinated Building Blocks

Aryls

Sulfonyl Chlorides

Chlorides

Ethers

Trifluoromethyls

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Log Po/w (iLOGP) :	2.01
Log Po/w (XLOGP3) :	3.13
Log Po/w (WLOGP) :	4.85
Log Po/w (MLOGP) :	1.71
Log Po/w (SILICOS-IT) :	1.97
Consensus Log Po/w :	2.74

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

Log S (ESOL) :	-3.53
Solubility :	0.0777 mg/ml ; 0.000298 mol/l
Class :	Soluble
Log S (Ali) :	-3.89
Solubility :	0.0339 mg/ml ; 0.00013 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.57
Solubility :	0.0703 mg/ml ; 0.00027 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	1.87

Signal Word:	Danger	Class:	8
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	3265
Hazard Statements:	H314	Packing Group:	Ⅱ
GHS Pictogram:

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

[ CAS No. 94108-56-2 ] {[proInfo.proName]}

Quality Control of [ 94108-56-2 ]

Related Doc. of [ 94108-56-2 ]

Product Details of [ 94108-56-2 ]

Calculated chemistry of [ 94108-56-2 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 94108-56-2 ]

Application In Synthesis of [ 94108-56-2 ]

[ 94108-56-2 ] Synthesis Path-Downstream 1~77

Related Functional Groups of [ 94108-56-2 ]

Fluorinated Building Blocks

Aryls

Sulfonyl Chlorides

Chlorides

Ethers

Trifluoromethyls

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 94108-56-2 ]