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CAS No. :103360-04-9 MDL No. :MFCD01631930
Formula : C7H6ClFO2S Boiling Point : -
Linear Structure Formula :- InChI Key :UUQGWVIRPCRTSA-UHFFFAOYSA-N
M.W : 208.64 Pubchem ID :2759108
Synonyms :

Safety of [ 103360-04-9 ]

Signal Word:Danger Class:8
Precautionary Statements:P261-P280-P305+P351+P338-P310 UN#:3261
Hazard Statements:H302-H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 103360-04-9 ]

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

  • Downstream synthetic route of [ 103360-04-9 ]

[ 103360-04-9 ] Synthesis Path-Downstream   1~53

  • 2
  • [ 907947-14-2 ]
  • [ 103360-04-9 ]
  • [ 907947-39-1 ]
YieldReaction ConditionsOperation in experiment
50% With triethylamine In tetrahydrofuran; dichloromethane at 40℃; B130.1 Triethylamine (0.3 mL) and (4-fluorophenyl)methanesulfonyl chloride (101 mg, 0.48 mmol) were added to a THF (5 mL)-dichloromethane (5 mL) solution of ethyl 2-amino-5-(4-chlorophenyl) indan-2-carboxylate hydrochloride (105 mg, 0.30 mmol), and stirred overnight at 40°C. 10% sodium bicarbonate solution was added to the reaction mixture, which was then extracted twice with ethyl acetate. The organic layers were combined, washed with 10% sodium bicarbonate solution and saturated sodium chloride solution, and dried by addition of magnesium sulfate. The drying agent was filtered out, and the mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: ethyl acetate/hexane = 1/10-1/1) to obtain ethyl 5-(4-chlorophenyl)-2-[(4-fluorobenzyl)sulfonyl]amino}indan-2-carboxylate (74 mg, 50%) as a colorless oil. 1H-NMR (300MHz, DMSO-d6) δ: 7.82 (1H, s), 7.69-7.66 (2H, d), 7.55-7.49 (4H, m), 7.34-7.32 (2H, d), 7.14-7.08 (4H, m), 4,27 (2H, s), 4.19-4.13 (2H, q), 3.54-3.44 (2H, t), 3.36-3.26 (2H, m), 1.23-1.18 (3H, t) LC-MS 510 [M+H]+
  • 3
  • [ 103360-04-9 ]
  • [ 75-86-5 ]
  • [ 308851-25-4 ]
YieldReaction ConditionsOperation in experiment
37% With triethylamine In dichloromethane at 0 - 20℃; XVIII.2'.1 4.48 g of 2-hydroxyisobutyronitrile are initially charged in 120 ml of methylene chloride and admixed with 7.2 g of triethylamine, 10 g of 4-fluorobenzyl-sulphonyl chloride are added dropwise at 0° C. and the mixture is stirred at room temperature for 6 h. The reaction solution is taken up in water and the organic phase is separated off, dried and concentrated. The residue is purified by silica gel chromatography using toluene/ether 10:1 as mobile phase. [1135] Yield: 5.1 g (+E,cir 37% of theory), m.p. 68° C.
37% With triethylamine In dichloromethane at 0 - 20℃; for 6h; XVIII-2'-1 Example XVIII-2'-1 4.48 g of 2-hydroxyisobutyronitrile are initially charged in 120 ml of methylene chloride and admixed with 7.2 g of triethylamine, 10 g of 4-fluorobenzyl-sulphonyl chloride are added dropwise at 0° C. and the mixture is stirred at room temperature for 6 h. The reaction solution is taken up in water and the organic phase is separated off, dried and concentrated. The residue is purified by silica gel chromatography using toluene/ether 10:1 as mobile phase. [01193] Yield: 5.1 g ( 37% of theory), m.p. 68° C.
  • 4
  • [ 450413-51-1 ]
  • [ 103360-04-9 ]
  • [ 450413-63-5 ]
YieldReaction ConditionsOperation in experiment
105 mg (75%) With triethylamine In dichloromethane 73 2-(3-{2-[(4-fluoro-phenylmethanesulfonyl)-heptyl-amino]-ethyl}-phenoxy)-2-methyl-butyric Acid EXAMPLE 73 2-(3-{2-[(4-fluoro-phenylmethanesulfonyl)-heptyl-amino]-ethyl}-phenoxy)-2-methyl-butyric Acid 4-Fluoro-α-toluenesulfonyl chloride (64 mg, 305 μmol) was added to a solution of 2-[3-(2-heptylamino-ethyl)-phenoxy]-2-methyl-butyric acid benzyl ester (100 mg, 234 μmol; Example 1), triethylamine (65 μL, 470 μmol) and methylene chloride (2 mL). The reaction mixture was stirred at ambient temperature for 6 h. Additional 4-fluoro-α-toluenesulfonyl chloride (16 mg, 76 μmol) and triethylamine (30 μL, 218 μmol) were added. After stirring another 24 h at ambient temperature, the reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over sodium sulfate, filtered, concentrated under reduced pressure and purified by flash column chromatography (9:1 hexanes/ethyl acetate) to provide 105 mg (75%) of 2-(3-{2-[(4-fluoro-phenylmethanesulfonyl)-heptyl-amino]-ethyl}-phenoxy)-2-methyl-butyric acid benzyl ester as a clear oil. Removal of the benzyl ester proceeded in a manner analogous to that described in Example 1. 97% yield. MS (APCI): 506 (M-H)-. 1H NMR (400 MHz, CDCl3) δ7.29 (m, 2H), 7.20 (m, 2H), 7.04 (m, 2H), 6.87 (d, 1H), 6.80 (d, 1H), 6.75 (s, 1H), 4.05 (s, 2H), 3.23 (t, 2H), 3.00 (t, 2H), 2.76 (t, 2H), 1.97 (m, 2H), 1.48 (s, 3H), 1.45 (m, 2H), 1.26 (m, 8H), 1.03 (t, 3H), 0.87 (t, 3H).
  • 5
  • [ 103360-04-9 ]
  • [ 500108-01-0 ]
YieldReaction ConditionsOperation in experiment
100% With ammonia In methanol 67.a Each of the following substances was made by reacting the corresponding sulfonyl chloride (0.75 mmol) with a saturated solution of ammonia in MeOH (5 mL). After evaporation of the ammonia and MeOH the residues were dissolved in MeOH (5 mL) and to a few samples DMF (2 mL) was also added to dissolve the reaction mixtures. The solutions where then separately filtered through ISOLUTE SCX-2, (25 mL cartridge) containing acidic ion exchange resin (propylsulphonic acid type, 5 g). MeOH (16 mL) was used to rinse the product from the resin. After removal of the solvent each of the products were used without further purification as described in Method A below. The sulfonamides made by this procedure are listed in table 1. Other sulphone amides were made via methods described in the examples or methods similar to those described.
100% With ammonia In tetrahydrofuran at 0 - 20℃; for 0.666667h; 67.a Ammonia gas was bubbled through THF (50 mL) at 0 °C for 5 minutes. l-(4- fluorophenyl)methanesulfonyl chloride (1.00 g, 4.80 mmol) was added to the reaction mixture and the system allowed to warm to r.t. Ammonia gas was bubbled through the system for 5 further minutes and the reaction mixture allowed to stir for a further 30 minutes. The reaction mixture was diluted with EtOAc (100 mL) and washed with saturated NH4Cl (2 x 50 mL), brine, dried (MgSO4) and concentrated under reduced pressure to afford l-(4- fluorophenyl)methanesulfonamide as a solid, which was used without further purification. Yield: 0.91 g (100 %).1HNMR (400 MHz, DMSO-d6): δ 4.26 (2H, s), 6.82 (2H, s), 7.18-7.24 (2H, m), 7.38-7.42 (2H, m).
1.9 g With ammonium hydroxide; ammonium carbonate In tetrahydrofuran at 20℃; for 1h;
With ammonia In acetone at 0℃; for 4h; 4.1.11. General procedure for preparation of sulfonyl-carbamates 12a-k General procedure: Various substituted BnCl 9a-k (2.5 mmol) and thiourea (0.19 g,2.5 mmol) were refluxed together in EtOH (2.5 mL) for 1 h. After removal of EtOH at reduced pressure, the obtained solid was slowly added to a mixture of NCS (1.33 g, 10 mmol), 2M HCl (0.68 mL) and MeCN (4 mL) over 30 min. After completion of the reaction, the MeCN was removed on a rotary evaporator. Then H2O (3 mL) was added, and the white solid was filtered and dried under an infrared lamp to afford10a-k (70%-93%), respectively, which did not require further purification.Then, 10a-k were treated with ammonia solution (1 mL) inacetone (2 mL) at 0 °C for 4 h. After removal of acetone at reduced pressure, the crude was extract with EtOAc, and the combined organic layers were washed with H2O, and brine. After drying over Na2SO4,filtering, and concentrating of the organic phase, the resulting yellow solid 11a-k was used directly in the next step. Finally, 11a-k and ethylchloroformate (1.2 eq) were refluxed together in the presence K2CO3(1.5 eq) in acetone (5.0 mL) for 4 h obtained 12a-k.

  • 6
  • [ 1123754-80-2 ]
  • [ 103360-04-9 ]
  • [ 1123754-25-5 ]
YieldReaction ConditionsOperation in experiment
83% With dmap; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; optical yield given as %ee;
  • 7
  • [ 1123754-96-0 ]
  • [ 103360-04-9 ]
  • [ 1123754-31-3 ]
YieldReaction ConditionsOperation in experiment
82% With dmap; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; optical yield given as %ee;
  • 8
  • [ 1033767-97-3 ]
  • [ 103360-04-9 ]
  • tert-butyl 5-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin-4-yl)-3-[(4-fluorobenzyl)sulfonyl]amino}-1H-indazole-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
19% With triethylamine In dichloromethane for 13h; Reflux; 13.A Example 13Atert-Butyl 5-(3,5-dicyano-2,6-dimethyl-l,4-dihydropyridin-4-yl)-3-[(4-fluorobenzyl)sulfonyl]- amino} - 1 H-indazole- 1 -carboxylate To 100 mg (0.256 mmol) tert-buiy 3-amino-5-(3,5-dicyano-2,6-dimethyl-l,4-dihydropyridin-4-yl)- lH-indazole-1-carboxylate (Example 3A) in dichloromethane (4 ml) were added 160 mg (0.77 mmol) (4-fluorophenyl)methanesulfonyl chloride and 0.11 ml (0.77 mmol) triethylamine. The mixture was stirred at reflux for 12 h. Then, further batches of 160 mg (0.77 mmol) (4-fluorophenyl)- methanesulfonyl chloride and 0.11 ml (0.77 mmol) triethylamine were added, and the mixture was again stirred at reflux for 1 h. After concentration under reduced pressure, the residue was dissolved in ethyl acetate and washed with brine. The aqueous layer was re-extracted with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative RP- ?PLC (acetonitrile/water gradient) to give 28 mg (19% of th.) of the title compound.LC-MS (method 3): R, = 2.47 min; MS (ESIpos): m/z = 563 (M+?)+.
  • 9
  • [ 1373845-90-9 ]
  • [ 103360-04-9 ]
  • [ 1373840-21-1 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 16h; E.a Method E Examples2-(4-bromophenyl)-5-cvclopropyl-6-[(2-([(4-fluorobenzyl)sulfonyllamino)ethyl)(methylsulfonyl)aminol-A/-methyl-2/-/-indazole-3-carboxamide (9)Step a: To a solution of Compound (7) (34 mg, 67 pmol) prepared according to Method D inDMF (3 mL) at 0 °C was added DIPEA (18 μ, 100 μηηοΙ) followed by 4- (fluorophenyl)methanesulfonyl chloride (17 mg, 81 pmol) and the mixture was left stirring for 16 h at T (monitored by LCMS). The solvent was removed in vacuo to give the crude mixture which was purified by flash column chromatography eluting with EtOAc/hexane (5- 100 %) to give partially purified product (34 mg, 75 %). A portion of this compound (10 mg) was purified further by preparative HPLC to give Compound (9) (3.34 mg). ESI-MS m/z calculated for [M+H]+: 678.09/680.08; found: 677.96/679.96. 1H NMR (400 MHz, CDCI3) δ 7.74 (s, 1 H), 7.67 (brd, J = 8.8 Hz, 2H), 7.47 (brd, J = 8.8 Hz, 2H), 7.40 - 7.31 (m, 3H), 7.09 - 6.98 (m, 2H), 5.82 (d, J = 4.7 Hz, 1 H), 4.70 (t, J = 6.1 Hz, 1 H), 4.23 (s, 2H), 3.92 - 3.68 (m, 2H), 3.15 (ddd, J = 14.9, 12.0, 6.1 Hz, 2H), 3.09 (s, 3H), 2.99 (d, J = 4.9 Hz, 3H), 2.35 - 2.19 (m, 1 H), 1.14 - 0.85 (m, 3H), 0.59 - 0.43 (m, 1 H).
  • 10
  • [ 103360-04-9 ]
  • [ 10523-68-9 ]
  • N-(2-adamantyl)-(4-fluorophenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% With sodium carbonate In diethyl ether; water at 20℃;
  • 11
  • [ 352-11-4 ]
  • [ 103360-04-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: ethanol / 0.5 h / Reflux 2: N-chloro-succinimide; hydrogenchloride / water; acetonitrile / 0.5 h / 10 - 20 °C / Green chemistry
Multi-step reaction with 2 steps 1: ethanol / 1 h / Reflux; Green chemistry 2: sodium chlorite; hydrogenchloride / acetonitrile / 0.5 h / 10 - 20 °C / Green chemistry
Multi-step reaction with 2 steps 1: ethanol / 1 h / Reflux 2: sulfuric acid; sodium hypochlorite / diethyl ether; water / 0.5 h / 0 - 20 °C / Green chemistry
Multi-step reaction with 2 steps 1: ethanol / 1 h / Reflux 2: tert-butylhypochlorite / acetonitrile; water / 0 - 20 °C
Stage #1: 1-chloromethyl-4-fluorobenzene With ethanol; thiourea at 96℃; for 3h; Inert atmosphere; Sealed tube; Stage #2: With hydrogenchloride In water; acetonitrile at 0℃; for 0.25h; Inert atmosphere; Sealed tube; Stage #3: With N-chloro-succinimide In water; acetonitrile at 20℃; for 0.5h; Inert atmosphere; Sealed tube;
Stage #1: 1-chloromethyl-4-fluorobenzene With thiourea In ethanol at 96℃; Stage #2: With hydrogenchloride In water; acetonitrile at 0℃; for 0.25h; Stage #3: With N-chloro-succinimide In water; acetonitrile at 20℃;
Stage #1: 1-chloromethyl-4-fluorobenzene With thiourea In ethanol at 96℃; for 3h; Stage #2: With hydrogenchloride; N-chloro-succinimide In ethanol; water; acetonitrile at 0 - 20℃; for 1.25h;
Multi-step reaction with 2 steps 1: ethanol / 1 h / Reflux 2: hydrogenchloride; N-chloro-succinimide / acetonitrile / 0.33 h / 10 - 20 °C
Stage #1: 1-chloromethyl-4-fluorobenzene With thiourea In ethanol for 1h; Reflux; Stage #2: With hydrogenchloride; N-chloro-succinimide In water; acetonitrile for 0.5h; 4.1.11. General procedure for preparation of sulfonyl-carbamates 12a-k General procedure: Various substituted BnCl 9a-k (2.5 mmol) and thiourea (0.19 g,2.5 mmol) were refluxed together in EtOH (2.5 mL) for 1 h. After removalof EtOH at reduced pressure, the obtained solid was slowly added to a mixture of NCS (1.33 g, 10 mmol), 2M HCl (0.68 mL) and MeCN (4 mL) over 30 min. After completion of the reaction, the MeCN was removed on a rotary evaporator. Then H2O (3 mL) was added, and the white solid was filtered and dried under an infrared lamp to afford 10a-k (70%-93%), respectively, which did not require further purification.Then, 10a-k were treated with ammonia solution (1 mL) inacetone (2 mL) at 0 °C for 4 h. After removal of acetone at reducedpressure, the crude was extract with EtOAc, and the combined organiclayers were washed with H2O, and brine. After drying over Na2SO4,filtering, and concentrating of the organic phase, the resulting yellowsolid 11a-k was used directly in the next step. Finally, 11a-k and ethylchloroformate (1.2 eq) were refluxed together in the presence K2CO3(1.5 eq) in acetone (5.0 mL) for 4 h obtained 12a-k.
Multi-step reaction with 2 steps 1: sodium sulfite / water; acetone / 12 h / Reflux 2: N,N-dimethyl-formamide; thionyl chloride / dichloromethane / Reflux
Multi-step reaction with 2 steps 1: ethanol / 1 h / Reflux 2: N-chloro-succinimide; hydrogenchloride / acetonitrile; water / 0.5 h / 0 - 20 °C
Multi-step reaction with 2 steps 1: ethanol / 80 °C 2: N-chloro-succinimide; hydrogenchloride / acetonitrile / 20 °C

Reference: [1]Yang, Zhanhui; Xu, Jiaxi [Synthesis, 2013, vol. 45, # 12, p. 1675 - 1682]
[2]Yang, Zhanhui; Zheng, Yongpeng; Xu, Jiaxi [Synlett, 2013, vol. 24, # 16, p. 2165 - 2169]
[3]Yang, Zhanhui; Zhou, Bingnan; Xu, Jiaxi [Synthesis, 2014, vol. 46, # 2, p. 225 - 229]
[4]Qiu, Kui; Wang, Rennan [Synthesis, 2015, vol. 47, # 20, p. 3186 - 3190]
[5]Bera, Milan; Maji, Arun; Sahoo, Santosh K.; Maiti, Debabrata [Angewandte Chemie - International Edition, 2015, vol. 54, # 29, p. 8515 - 8519]
[6]Bera, Milan; Agasti, Soumitra; Chowdhury, Rajdip; Mondal, Rahul; Pal, Debasis; Maiti, Debabrata [Angewandte Chemie - International Edition, 2017, vol. 56, # 19, p. 5272 - 5276][Angew. Chem., 2017, vol. 129, # 19, p. 5356 - 5360]
[7]Modak, Atanu; Patra, Tuhin; Chowdhury, Rajdip; Raul, Suman; Maiti, Debabrata [Organometallics, 2017, vol. 36, # 13, p. 2418 - 2423]
[8]Kong, Deyu; Xue, Tao; Guo, Bin; Cheng, Jianjun; Liu, Shunyin; Wei, Jianhai; Lu, Zhengyu; Liu, Haoran; Gong, Guoqing; Lan, Tian; Hu, Wenhao; Yang, Yushe [Journal of Medicinal Chemistry, 2019, vol. 62, # 6, p. 3088 - 3106]
[9]Nan, Xiang; Jiang, Yi-Fan; Li, Hui-Jing; Wang, Jun-Hu; Wu, Yan-Chao [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 13, p. 2801 - 2812]
[10]Current Patent Assignee: CHANGSHA WEICHU PHARMACEUTICAL TECH - CN110981760, 2020, A
[11]Fang, Sen-Biao; Li, Hui-Jing; Nan, Xiang; Wu, Rui; Wu, Yan-Chao; Zhang, Jing; Zhang, Zhi-Zhou [European Journal of Medicinal Chemistry, 2020, vol. 200]
[12]Current Patent Assignee: TECHNODERMA MEDICINES; JIAXING TEKELUO BIOTECHNOLOGY - CN111961037, 2020, A
  • 12
  • [ 122305-64-0 ]
  • [ 103360-04-9 ]
YieldReaction ConditionsOperation in experiment
97% With tert-butylhypochlorite In water; acetonitrile at 0 - 20℃; Sulfonyl Chlorides 3; General Procedure General procedure: Alkyl halide (or sulfate) (5 mmol) and thiourea (0.381 g, 5 mmol) were heated at reflux in EtOH (5 mL) for 1 h. After removal of the solvent in vacuum and washing with Et2O (3 × 5 mL), the corresponding S-alkyl isothiourea salt was obtained as a white solid in almost quantitative yield. Without purification, the product was transferred into a three-necked round-bottom flask equipped with a thermometer and an addition funnel in an ice-bath, followed by addition of water (0.45mL) and MeCN (10 mL). To the resultant vigorously stirred mixture was added dropwise a solution of t-BuOCl (2.86 mL) in MeCN (5 mL), keeping the inner temperature at 0-20 °C. The mixture was then stirred for 30 min. Removal of the solvent under vacuum, addition of Et2O (15 mL), washing with H2O (2 × 10 mL), drying over Na2SO4, and concentration under vacuum gave the desired product in high purity. The product was further purified by recrystalization from petroleum ether-EtOAc.
1.022 g With hydrogenchloride; N-chloro-succinimide In water; acetonitrile at 10 - 20℃; for 0.5h; Green chemistry;
0.776 g With hydrogenchloride; sodium chlorite In acetonitrile at 10 - 20℃; for 0.5h; Green chemistry; General Procedure for the Synthesis of Sulfonyl Chlorides from Alkyl Halidesand Thiourea General procedure: Step 1. An alkyl halide or mesylate (5 mmol) and thiourea (0.381 g, 5 mmol) wererefluxed in 5 mL of ethanol for 1 h. After removal of the solvent in vacuum thecorresponding S-alkyl isothiourea salt was obtained as white solid or sticky oil.Step 2. A 50 mL three-necked flask equipped with a thermometer and asolid-addition funnel was immersed in an ice-bath. To the flask was sequentiallyadded NaClO2 solid (for isothiouronium chlorides or sulfonate, 1.61 g, 15 mmol; forisothiouronium bromides, 2.14 g, 20 mmol, 85% purity), MeCN (10 mL), and thenconc. HCl (for isothiouronium chlorides or sulfonate, 3 mL; for isothiouroniumbromides, 4 mL) during 1 min at such a rate that the inner temperature was maintainedless than 10 °C. Then S-alkyl isothiourea salt was slowly added througth the solidaddition-funnel to keep the inner temperature less than 20 °C. After the addtion, theresulting mixture was stirred for another 30 min. Then 25 mL of water was added, and the resultant mixture was evaporated in vacuum at 15 °C to remove acetonitrile. Afteraddition of 100 mL of water, the solid products were obtained by filtration on aBuchner funnel and dried under an infrared lamp, while the liquid products wereobtained by extraction with 15 mL of ethyl acetate, drying with Na2SO4, andconcentration in vacuum.For 1,4-dibromobutane, the amounts of thiourea, NaClO2 solid, MeCN, and conc.HCl were doubled.
1.066 g With sodium hypochlorite; sulfuric acid In diethyl ether; water at 0 - 20℃; for 0.5h; Green chemistry; Sulfonyl Chlorides 3a-h,m-p; General Procedure General procedure: The appropriate alkyl halide (or mesylate) (5 mmol) and thiourea (0.381 g, 5 mmol) were refluxed in EtOH (5 mL) for 1 h. After removal of the solvent in vacuum and washing with Et2O (3 × 5 mL), the corresponding S-alkyl isothiourea salt was obtained as a white solid or sticky oil in an almost quantitative yield. Without purification, the product was transferred into a three-necked round-bottomed flask equipped with a thermometer and an addition funnel in an ice-bath. Then, 6 M H2SO4 (2 mL), followed by Et2O (30 mL) were added. To the resultant vigorously stirred mixture was added dropwise 5% bleach (for alkyl chlorides and mesylates, 30 mL; foralkyl bromides, 37.5 mL) by keeping the inner temperature 0-20 °C (for the preparation of alkanedisulfonyl dichlorides, 0.762 g, 10 mmol thiourea, 4 mL of 6 M H2SO4, 50 mL of Et2O, and 75 mL of 5% bleach were used). After the addition, the mixture was stirred for another 30 min. The mixture was partitioned in a separatory funnel, and the ethereal phase was washed with brine (25 mL), dried (Na2SO4), and evaporated in vacuum to afford the desired product. The oily products were extracted with CHCl3 (3 × 2.5 mL) and evaporated to remove the by-product, bromine. If necessary, the products can be dissolved in minimal PE-EtOAc (5:1) and filtered through a column of silica gel (h = 5 cm) with PE-EtOAc (5:1) as eluent to remove the impurities (Table 2).
With hydrogenchloride; N-chloro-succinimide In acetonitrile at 10 - 20℃; for 0.333333h;
With hydrogenchloride; N-chloro-succinimide In water; acetonitrile at 0 - 20℃; for 0.5h; 4.1.3. General procedure for preparation of sulfonyl azides 24a-k General procedure: Various alkyl halides 23a-k (2.5 mmol) and thiourea (0.19 g, 2.5 mmol) were refluxed together in EtOH (2.5 mL) for 1 h. Afterr emoval of EtOH at reduced pressure, the obtained solid was slowly added to a mixture of NCS (1.33 g, 10 mmol), 2 M HCl (0.68 mL) and MeCN (4 mL) over 15 min. Upon completion of the reaction (TLC monitoring), the solvent was removed under vacuum. Then H2O(5 mL)was added to the residue and stirred for 15 min, the resulting solid was filtered and dried under an infrared lamp to afford the corresponding sulfonyl chlorides 24a-k. Without further purification, 24a-k was added in portions to a solution of NaN3 (195 mg ,3 mmol) in acetone/H2O (10 mL, acetone/H2O = 1:1) at 0 °C. After being stirred at room temperature for 4 h, the reaction mixtur ewas concentrated in vacuo and H2O (10 mL) was added to the residue. The aqueous solution was extracted with CHCl3 (3 x 10 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford sulfonyl azides 25a-k.

  • 15
  • (S)-methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-amino-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate [ No CAS ]
  • [ 103360-04-9 ]
  • C31H41FN4O6S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In tetrahydrofuran for 18h; 8 To a solution of (S)-methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1 -yl)-2-amino-7-methylimidazo [1 ,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate (30 mg,0.067 mmol) and TEA (28.2 jiL, 0.202 mmol, 3 equiv) in THF (0.45 mL) was added(4-fluorophenyl)methanesulfonyl chloride (28.2 mg, 0.135 mmol, 2 equiv) and stirred18 h. To the reaction was then added water (0.45 mL), MeOH (0.45 mL), and LiOHmonohydrate (160 mg, 4.05 mmol, 30 equiv). The reaction was heated at 50 °C for 2h. Upon cooling to ambient temperature, the mixture was filtered and purified via preparative LC/MS with the following conditions: Column: XBridge C18, 19 x mm,5-tim particles; Mobile Phase A: 5:95 methanol: water with 10-mM ammonium acetate; Mobile Phase B: 95:5 methanol: water with 10-mM ammonium acetate;Gradient: 50-90% B over 20 minutes, then a 5-minute hold at 100% B; Flow: 20mL/min to provide the product (40.6 mg, 100%). ‘H NMR (500 MHz, DMSO-d6) ö7.43-7.36 (m, 2H), 7.27-7.07 (m, 4H), 6.11 -5.99 (m, 1H), 5.89 (br. s., 1H), 5.37(d, J 16.2 Hz, 1H), 5.15 (d, J 9.2 Hz, 1H), 4.60 - 4.55 (m, 2H), 4.00 - 3.95 (m,2H), 3.70 - 3.62 (m, 2H), 2.99 - 2.91 (m, 1H), 2.66 - 2.58 (m, 1H), 2.39 (s, 3H), 1.88- 1.63 (m, 4H), 1.24 (s, 3H), 1.18 (s, 9H); LCMS (ESI, M): 602.3.
  • 16
  • [ 1354041-25-0 ]
  • [ 103360-04-9 ]
  • C24H18F2N6O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
17% With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 90℃; for 18h; 1 To a solution of Intermediate 2 (1 equiv.) in dichioromethane was added (4-fluorophenyl)methanesulfonyl chloride (1 equiv.), followed by DBU (1 equiv.). The reaction was stirred at 90 °C for 18 h. The reaction mixture was diluted with water, extracted with dichloromethane (3x), washed with iN hydrochloric acid solution (2x), dried (sodium sulfate), filtered, and concentrated in vacuo. Purification of the crude material via reverse phase HPLC delivered the desired compound, Compound 1-491 (17.8 mg, 17% yield) as a solid.1H NMR (500 MHz, CDC13) ö ppm 8.52 (d, 1 H), 8.28 (br. s., 1 H), 7.38 (br. s., 1 H), 7.30 (dd, 2 H), 7.25 (br. s., 1 H), 7.14-6.97 (m, 4 H), 6.92-6.73 (m, 3 H), 6.63 (d, 1 H), 5.91 (s, 2 H), 4.54 (br. s., 2 H).
  • 17
  • (E)-4-{2-[2'-(aminomethyl)biphenyl-2-yl]vinyl}phenyl acetate [ No CAS ]
  • [ 103360-04-9 ]
  • (E)-1-(4-fluorophenyl)-N-((2'-(4-hydroxystyryl)biphenyl-2-yl)methyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
24 mg Stage #1: (E)-4-{2-[2'-(aminomethyl)biphenyl-2-yl]vinyl}phenyl acetate; 4-fluorobenzylsulfonyl chloride With N-ethyl-N,N-diisopropylamine for 48h; Stage #2: With methanol; sodium hydroxide at 20℃; for 1h; 24 (E)-1-(4-fluorophenyl)-N-((2’-(4-hydroxystyryl)biphenyl-2-yl)methyl)methanesulfonamide (47): A solution of 11 (0.102 mmol) was treated withDIPEA (89 uL, 0.511 mmol) and 4-fluorobenzylsulfonyl chloride (23 mg, 0.122 mmol). The reaction was stirred for 24 h, after which another aliquot of 4- fluorobenzylsulfonyl chloride (23 mg, 0.122 mmol) was added. After a further 24 h, the reaction was filtered through a plug of silica and the volatile components wereremoved by evaporation. The resulting crude material was dissolved in MeOH (1 mL) and treated with 1 M NaOH (204 uL, 0.204 mmol) and stirred at room temperature. After 1 h, the solvents were removed by evaporation and the crude product was purified by flash chromatography to afford 47 (24 mg) as a white solid. ‘H NMR (400 MHz, CDC13) ö = 7.78 (d, J = 7.8 Hz, 1H), 7.51 -7.39 (m, 4H), 7.32 (td, J = 7.5, 1.1 Hz, 1H),7.27 - 7.24 (m, 1H), 7.14 (d, J = 8.6 Hz, 2H), 7.08 (dd, J = 7.6, 1.2 Hz, 1H), 7.05 - 7.00(m, 2H), 6.99 - 6.89 (m, 3H), 6.73 (d, J = 8.6 Hz, 2H), 6.54 (d, J = 16.3 Hz, 1H), 5.75(bs, 1H), 4.02 - 3.89 (m, 4H). ‘3C NMR (100 MHz, CDC13) ö = 171.7, 164.2, 161.7,156.0, 140.5, 138.8, 136.0, 135.3, 132.3, 132.3, 130.6, 130.3, 130.0, 129.7, 129.0,128.4, 128.4, 128.3, 128.1, 127.4, 125.3, 124.9, 124.8, 123.9, 116.0, 115.8, 115.8, 58.4,45.6.
  • 18
  • [ 611-20-1 ]
  • [ 103360-04-9 ]
  • 2-cyanophenyl (4-fluorophenyl)methanesulfonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% Stage #1: salicylonitrile With sodium hydride In tetrahydrofuran; mineral oil for 0.166667h; Inert atmosphere; Sealed tube; Stage #2: 4-fluorobenzylsulfonyl chloride In tetrahydrofuran; mineral oil at 20℃; Inert atmosphere; Sealed tube;
  • 19
  • [ 103360-04-9 ]
  • [ 106-49-0 ]
  • C14H14FNO2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine at 80℃; for 4h; 3.D.1 General procedure: 4.3.1 4-methyl-N-(3-(trifluoromethyl)phenyl)benzenesulfonamide (11aa) 4-methylbenzenesulfonyl chloride (9a) (1.4 g, 7.4 mmol) and 3-(trifluoromethyl) aniline (10a) (1.0 g, 6.2 mmol) were added in pyridine. The reaction mixture was heated to 80 °C for 4 h. Hydrochloric acid was added, and the aqueous layer was extracted with ethyl acetate (150 mL * 3). The organic layer was combined and washed with saturated sodium chloride (50 mL), dried with Na2SO4 and evaporated. The resulting crude product was purified by silica gel chromatography with petroleum ether/ethyl acetate (4/1, v/v) to afford 11aa as a white solid (1.9 g, 97% yield). For thesynthesis of 11ab-11df, please refer to 11aa.
  • 20
  • [ 103360-04-9 ]
  • C14H20N2O2 [ No CAS ]
  • (S)-3-(pyridin-3-yl)propyl 1-((4-fluorobenzyl)sulfonyl)piperidine-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.23 g With NMM or DIPEA In dichloromethane at 0℃; General procedure for the synthesis of compounds S-5a, b, n-y General procedure: According to a procedure of Choi et al.36 (S)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid (1equiv) was dissolved in 20mL anhydrous CH2Cl2 and at 0°C the corresponding alcohol (1.0equiv), EDC·HCl (1.5equiv) and DMAP (0.2equiv) were added. After the reaction was completed (TLC control) the organic layer was washed twice with water and the solvent was evaporated in vacuo. The boc-protection group was cleaved with 2mL trifluoroacetic acid in 20mL CH2Cl2. After 24h the reaction was neutralized with saturated NaHCO3 extracted with 3×30mL CH2Cl2. The combined organic layers were dried over Na2SO4 and the solvent was evaporated to yield compound 8a, b, n-y which was used in the next step without further purification. Compound 8a, b, n-y (1equiv) was dissolved in 40mL of anhydrous CH2Cl2, and NMM or DIPEA (3equiv) was added at 0°C followed by corresponding sulfonyl chloride (1equiv), respectively. The mixture was stirred until completion (TLC) and subsequently the solvent removed in vacuo. After purification by means of flash-chromatography compounds S-5a, b, n-y were obtained.
  • 21
  • [ 103360-04-9 ]
  • 1-(adamantan-1-ylmethyl)-6-amino-3,4-dihydroquinolin-2(1H)-one [ No CAS ]
  • N-[1(adamantan-1-ylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]-1-(4-fluorophenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% With pyridine In acetonitrile at 20℃; for 12h; Inert atmosphere; A46-158 6-Nitro-3,4-dihydroquinolin-2(1H)-one (2.00 g, 10.41 mmol) was dissolved under argon in abs. N,N-dimethylformamide and admixed with fine potassium carbonate powder (4.31 g, 31.22 mmol). After stirring at room temperature for 5 min, 1-bromomethyladamantane (3.10 g, 13.53 mmol) and potassium iodide (0.86 g, 5.20 mmol) were added. The resulting reaction mixture was stirred at 120° C. for 5 h and, after cooling to room temperature, water and ethyl acetate were added. The aqueous phase was then repeatedly extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 1-(adamantan-1-ylmethyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one (1.01 g, 29% of theory) was isolated as a colorless solid. In the next step, 1-(adamantan-1-ylmethyl)-6-nitro-3,4-dihydroquinolin-2(1H)-one (1.01 g, 2.97 mmol) was added together with tin(II) chloride dihydrate (2.68 g, 11.87 mmol) to abs. ethanol (30 mL) and the mixture was stirred under argon at a temperature of 50° C. for 3 h. After cooling to room temperature, the reaction mixture was poured into ice-water and then adjusted to pH 12 using aqueous NaOH. The aqueous phase was then repeatedly extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 1-(adamantan-1-ylmethyl)-6-amino-3,4-dihydroquinolin-2(1H)-one (0.86 g, 94% of theory) was isolated as a colorless solid. 1H-NMR (400 MHz, CDCl3 δ, ppm) 6.94 (d, 1H), 6.55-6.52 (m, 2H), 3.79-3-30 (br. s, 2H, NH), 3.54 (m, 2H), 2.79 (m, 2H), 2.59 (m, 2H), 1.89 (m, 3H), 1.66 (m, 2H), 1.63 (m, 2H), 1.58 (m, 4H), 1.49 (m, 4H). 1-(Adamantan-1-ylmethyl)-6-amino-3,4-dihydroquinolin-2(1H)-one (230 mg, 0.74 mmol) was dissolved together with (4-fluorophenyl)methanesulfonyl chloride (232 mg, 1.11 mmol) in abs. acetonitrile (7 mL) in a baked-out round-bottom flask under argon, then pyridine (0.12 mL, 1.48 mmol) was added and the mixture was stirred at room temperature for 12 h. The reaction mixture was then concentrated under reduced pressure, the remaining residue was admixed with dil. HCl and dichloromethane, and the aqueous phase was extracted repeatedly with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), N-[1-(adamantan-1-ylmethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]-1-(4-fluorophenyl)methanesulfonamide (210 mg, 59% of theory) was isolated as a colorless solid. 1H-NMR (400 MHz, CDCl3 δ, ppm) 7.29 (m, 2H), 7.10-7.02 (m, 3H), 6.98 (m, 1H), 6.87 (m, 1H), 6.06 (s, 1H, NH), 4.33 (s, 2H), 2.85 (m, 2H), 2.63 (m, 2H), 1.91 (m, 3H), 1.67 (m, 3H), 1.62-1.47 (m, 9H), 1.28 (m, 2H).
  • 23
  • [ 39835-11-5 ]
  • [ 103360-04-9 ]
  • C20H18FNO6S [ No CAS ]
  • 24
  • [ 39835-11-5 ]
  • [ 103360-04-9 ]
  • 2-cyano-5-methoxyphenyl (4-fluorophenyl)methanesulfonate [ No CAS ]
  • 25
  • [ 103360-04-9 ]
  • [octahydro-1H-cyclopenta[b]pyridin-4a-yl]methyl N-cyclopentylcarbamate [ No CAS ]
  • [1-[(4-fluorophenyl)methanesulfonyl]hexahydro-2H-cyclopenta[b]pyridin-4a-yl]methyl N-cyclopentylcarbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
31% With triethylamine In tetrahydrofuran at 20℃; Inert atmosphere; General procedure for sulfonylation: General procedure: Reactions were performed in parallel in 15 mlreaction tubes in a 24 position Mettler-Toledo Miniblock equipped with a heat transferblock and inert gas manifold. Each reaction tube was loaded with TEA (5.0 eq) and apreviously prepared solution of 30 mg of the corresponding intermediate in 1mL of dry THF.Then the corresponding sulfonyl chlorides (1.5 eq) were added. The reactions were stirred atroom temperature overnight. The mixtures were evaporated until dryness. The crudes wererediluted in 1.0 mL of ACN, filtered and purified with preparative HPLC.
  • 26
  • [ 103360-04-9 ]
  • [ 328-74-5 ]
  • N-(3,5-bis(trifluoromethyl)phenyl)-1-(4-fluorophenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With triethylamine In dichloromethane at 20℃; for 12h;
  • 27
  • [ 103360-04-9 ]
  • [ 108124-67-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: ethanol / 80 °C 2: [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate / water; ethanol / 40 h / Irradiation
  • 30
  • [ 103360-04-9 ]
  • 6-amino-4-ethyl-4-methyl-1-(4-methylcyclohexyl)-3,4-dihydroquinolin-2(1H)-one [ No CAS ]
  • N-[4-ethyl-4-methyl-1-(4-methylcyclohexyl)-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl]-1-(4-fluorophenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
35% With pyridine In dichloromethane at 0 - 20℃; for 1h; D1-158 No. D1-158: N-[4-Ethyl-4-methyl-1 -(4-methylcy- clohexyl)-2-oxo-1 ,2,3,4-tetrahydroquinolin-6-yl] -1-(4-fluorophenyl)methanesulfonamide 4-Ethyl-4-methyl-6-nitro-3,4-dihydroquinolin-2(1H)-one (1000 mg, 4.27 mmol) was dissolved in a microwave vessel in abs. 1,4-dioxane (10 ml), and the following were added at room temperature: finely powdered cesium carbonate (4180 mg, 12.82 mmol), 4-methylcyclohexyl bromide (1450 mg, 8.24 mmol) and finely powdered potassium iodide (71 mg, 0.43 mmol). The resulting reaction mixture was then stirred in a microwave apparatus at a temperature of 150° C. for one hour and, afier cooling to room temperature, concentrated under reduced pressure. The resulting residue was taken up with ethyl acetate, water was added, and the water phase was thoroughly extracted repeatedly with ethyl acetate. The combined organic phases were washed with sat. sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 4-ethyl-4-methyl- 1 -(4-methylcyclohexyl)-6-nitro-3,4-dihydroquinolin-2(1 H)- one (950 mg, 67% of theory) was isolated as a colorless solid. ‘H-NMR (400 MHz, CDC13 ö, ppm) 8.16-8.05 (m, 2H), 7.22 (m, 1H), 4.16 (m, 1H), 2.26 (q, 2H), 2.22 (m, 2H),1.89-1.62 (m, 6H), 1.56 (d, 3H), 1.32 (s, 3H), 1.18-1.04 (m, 3H), 0.93 (t, 3H). 4-Ethyl-4-methyl-1-(4-methylcyclo- hexyl)-6-nitro-3,4-dihydroquinolin-2(1 H)-one (800 mg, 2.42 mmol) was dissolved in methanol, and ammonium chloride (642 mg, 12.10 mmol), zinc powder (786 mg, 12.10 mmol) and water (0.8 ml) were added. The resulting reaction mixture was stirred at room temperature for one hour, then filtered through Celite, washed with methanol and concentrated under reduced pressure. The remaining residue was taken up with ethyl acetate, water was added, and the water phase was thoroughly extracted repeatedly with ethyl acetate. The combined organic phases were then washed with sat. sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 6-amino-4-ethyl-4-methyl- 1 -(4- methylcyclohexyl)-3,4-dihydroquinolin-2(1 H)-one (550 mg, 87% of theory) was isolated as a colorless solid. ‘H-NMR (400 MHz, CDC13 ö, ppm) 6.96 (d, 1H), 6.58-6.51 (m, 2H), 4.12 (m, 1H), 3.58 (bt s, 2H), 2.52-2.37 (m, 4H), 1.94-1.58 (m, 6H), 1.56 (d, 3H), 1.20 (s, 3H), 1.15-1.02 (m, 3H), 0.92 (t, 3H). 6-Amino-4-ethyl-4-methyl-1-(4-methyl- cyclohexyl)-3,4-dihydroquinolin-2(1 H)-one (100 mg, 0.33 mmol) was dissolved in dichloromethane (5 mE) and cooled down to 0° C., and pyridine (0.13 ml, 1.66 mmol) and 4-fluorophenylmethanesulfonyl chloride (79 mg, 0.37 mmol) were added. The resulting reaction mixture was then stirred at room temperature for one hour and then water and dichioromethane were added, and thorough extraction was effected. The aqueous phase was reextracted repeatedly with dichioromethane, and the combined organic phases were dried over sodium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), N-[4-ethyl-4-methyl- 1 -(4-methylcyclohexyl)-2-oxo-1, 2,3,4-tetrahydroquinolin-6-yl]-1 -(4-fluorophenyl)methane- sulfonamide (55 mg, 35% of theory) was isolated as a colorless solid. ‘H-NMR (400 MHz, CDC13 ö, ppm) 7.27 (m, 2H), 7.14-7.02 (m, 4H), 6.93 (s, 1H), 6.08 (br. s, 1H, NH), 4.29 (s, 2H), 4.12 (m, 1H), 2.57-2.37 (m, 4H), 1.89- 1.58 (m, 6H), 1.24 (s, 3H), 1.15-1.02 (m, 3H), 0.94 (d, 3H),0.84 (t, 3H).
  • 31
  • [ 103360-04-9 ]
  • 2-(9H-carbazol-1-yl)aniline [ No CAS ]
  • N-(2-(9H-carbazol-1-yl)phenyl)-1-(4-fluorophenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With pyridine In dichloromethane at 20℃; Inert atmosphere; General Procedure A: Sulfonamide/carboxamide synthesis General procedure: To a stirred solution of 2-(9H-carbazol-1-yl)aniline (1 eq) in CH2Cl2 (0.1 M, anhydrous) was added pyridine (1.3 eq) followed by sulfonyl chloride or acid chloride (1.1 eq) and the solution was allowed to stir at room temperature under a nitrogen atmsophere. Upon reaction completion the crude mixture was concentrated onto silica gel and purified by Isolera Biotage LPLC (CH/EA 8:2) to afford pure sulfonamide/amide.
  • 32
  • [ 103360-04-9 ]
  • [ 131922-05-9 ]
  • 1-[(4-fluorophenyl)methylsulfonyl]-3-(trifluoromethyl)piperazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With triethylamine; In dichloromethane; at 0 - 20℃; 2-(Trifluoromethyl)-piperazine (2 g, 13 mmol) and TEA (2.17 ml, 15.6 mmol) were dissolved in DCM (30 ml). (4-fluorophenyl)methanesulfonyl chloride(2.71 g, 13 mmol) was added in small portions at 0 00 and the mixture was stirred at rt overnight. Water (45 ml) was added and the mixture extracted with DCM (2 x 80 ml). The combined organics were washed twice with brine, dried over Na2504, filtered and concentrated to give the product as a solid (3.5 g, 83%). MS ES+ m/z 327 [M+H].
83% With triethylamine; In dichloromethane; at 0 - 20℃; 2-(Trifluoromethyl)-piperazine (2 g, 13 mmol) and TEA (2.17 ml, 15.6 mmol) were dissolved in DCM (30 ml). (4-fluorophenyl)methanesulfonyl chloride (2.71 g, 13 mmol) was added in small portions at 0 C and the mixture was stirred at rt overnight. Water (45 ml) was added and the mixture extracted with DCM (2 x 80 ml). The combined organics were washed twice with brine, dried over Na2SO4, filtered and concentrated to give the product as a solid (3.5 g, 83%). MS ES+ m/z 327 [M+H]+.
  • 33
  • [ 103360-04-9 ]
  • [ 131922-05-9 ]
  • 1-(4-benzyloxy-6-tert-butoxy-2-pyridyl)-4-[(4-fluorophenyl)methylsulfonyl]-2-(trifluoromethyl)piperazine [ No CAS ]
  • 34
  • [ 103360-04-9 ]
  • C16H23NO3 [ No CAS ]
  • C23H28FNO5S [ No CAS ]
YieldReaction ConditionsOperation in experiment
220 mg With triethylamine In dichloromethane at 0 - 20℃; 9.e Example 9
Preparation of methyl 2-(S)-N-(4-fluorobenzylidenesulfonyl)-artemisinic acid (1i): Step a-d of this embodiment is performed according to the embodiment 1: e, 263 mg of 2-(S)-amino-insulinic acid methyl ester was dissolved in anhydrous dichloromethane.Add 200 μL of triethylamine,Cool the reaction system to 0 ° C in an ice water bath.170 μL of 4-fluorobenzenemethanesulfonyl chloride was added dropwise.Raise to room temperature overnight, after TLC detects the reaction,Dichloromethane was added, washed twice with water, the organic phase was dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated in vacuo. The residue was eluted by column chromatography eluting with petroleum ether of 7:1 by volume. : ethyl acetate,Amide substituted methyl acetonate derivative 2-(S)-N-(4-fluorophenylmethanesulfonyl)-artemisinic acid methyl ester (1i) 220mg;
  • 35
  • [ 103360-04-9 ]
  • 2-(pyrimidin-5-yl)phenol [ No CAS ]
  • 2-(pyrimidin-5-yl)phenyl (4-fluoro-3-((triisopropylsilyl)ethynyl)phenyl)methanesulfonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 20 °C / Inert atmosphere 2: palladium diacetate; N-acetylglycine; silver(I) acetate; copper diacetate / 1,4-dioxane / 24 h / 80 °C
  • 36
  • C8H9FN2S*H(1+) [ No CAS ]
  • [ 103360-04-9 ]
YieldReaction ConditionsOperation in experiment
Stage #1: C8H9FN2S*H(1+) With hydrogenchloride In acetonitrile at 0℃; for 0.25h; Stage #2: With N-chloro-succinimide In acetonitrile at 20℃; for 0.5h;
  • 37
  • [ 103360-04-9 ]
  • [ 593-51-1 ]
  • C8H10FNO2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane at 0 - 20℃; for 3h; 1 Compound c (1eq) was dissolved in DCM (2V) and added dropwise to an DCM solution (5V) in which 1.5eq of methylamine hydrochloride was dissolved in an ice bath (0 degrees Celsius). After the addition was completed, the temperature was slowly raised to room temperature At room temperature, stirring for 3 hours, TLC detection reaction.When the raw materials are consumed, add water (50mL) to quench the excess sulfonyl chloride, then extract the reaction solution with DCM (60 * 3mL), combine the organic phases, wash with saturated brine, add 20g anhydrous sodium sulfate to dry until the system is anhydrous, and filter And concentrated under reduced pressure to obtain the crude product through column chromatography to obtain compound d. The chromatographic solution was (DCM: MeOH = 20: 1), yield: 60%.
  • 38
  • [ 103360-04-9 ]
  • [ 557-66-4 ]
  • C9H12FNO2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane at 0 - 20℃; for 3h; 2 Compound c1(1eq) was dissolved in DCM (as little as possible) and added dropwise to an DCM solution of ethylamine hydrochloride in an ice bath (0 degrees Celsius). After the addition was completed, the temperature was slowly raised to room temperature at room temperature. Under conditions, stirring for 3 hours, the reaction was detected by TLC.When the raw materials were consumed, water (50 mL) was added to quench the excess sulfonyl chloride, and then the reaction solution was extracted with DCM (60 * 3 mL). The organic phases were combined and washed with saturated brine, dried with an appropriate amount of anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The obtained crude product was subjected to column chromatography to obtain compound d1, and the chromatography solution was (DCM: MeOH = 20: 1), yield: (72)%.
  • 39
  • C7H7FO3S [ No CAS ]
  • [ 103360-04-9 ]
YieldReaction ConditionsOperation in experiment
With thionyl chloride; N,N-dimethyl-formamide In dichloromethane Reflux; 1; 2 Compound b (1 eq) was dissolved in DCM (10V), 3 (eq) of dichlorosulfoxide was added, and then 0.05 mL of DMF was added dropwise, and the temperature was raised to reflux and stirred until the raw materials were consumed.The solvent was removed under reduced pressure to obtain the crude compound c. Due to the instability of compound c, it was used directly without further post-treatment.
  • 40
  • [ 103360-04-9 ]
  • (4-fluorophenyl)methanesulfonyl azide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium azide In water; acetone at 0 - 20℃; for 4h; 4.1.3. General procedure for preparation of sulfonyl azides 24a-k General procedure: Various alkyl halides 23a-k (2.5 mmol) and thiourea (0.19 g, 2.5 mmol) were refluxed together in EtOH (2.5 mL) for 1 h. Afterr emoval of EtOH at reduced pressure, the obtained solid was slowly added to a mixture of NCS (1.33 g, 10 mmol), 2 M HCl (0.68 mL) and MeCN (4 mL) over 15 min. Upon completion of the reaction (TLC monitoring), the solvent was removed under vacuum. Then H2O(5 mL)was added to the residue and stirred for 15 min, the resulting solid was filtered and dried under an infrared lamp to afford the corresponding sulfonyl chlorides 24a-k. Without further purification, 24a-k was added in portions to a solution of NaN3 (195 mg ,3 mmol) in acetone/H2O (10 mL, acetone/H2O = 1:1) at 0 °C. After being stirred at room temperature for 4 h, the reaction mixtur ewas concentrated in vacuo and H2O (10 mL) was added to the residue. The aqueous solution was extracted with CHCl3 (3 x 10 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford sulfonyl azides 25a-k.
  • 41
  • [ 103360-04-9 ]
  • [ 2450-71-7 ]
  • N-propargyl-1-(4-fluorophenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; Schlenk technique;
  • 42
  • [ 103360-04-9 ]
  • tert-butyl 1,4-trans-N-[4-[[6-(4-amino-3-fluoro-phenyl)-8-(fluoromethyl)pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carbamate [ No CAS ]
  • tert-butyl 1,4-trans-N-[4-[[6-[3-fluoro-4-[(4-fluorophenyl)methylsulfonylamino]phenyl]-8-(fluoromethyl)pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
31% With pyridine In dichloromethane at 20℃; 29.6 Step 6: tert-Butyl 1,4-trans-N-[4-[[6-[3-fluoro-4-[(4-fluorophenyl)methylsulfonyl- amino]phenyl]-8-(fluoromethyl)pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carbamate tert-Butyl 1,4-trans-N-[4-[[6-(4-amino-3-fluoro-phenyl)-8-(fluoromethyl)pyr- ido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carbamate (29 mg, 0.06 mmol) was dissolved in CH2Cl2 (1 mL) and to the solution was added pyridine (141 mg, 1.8 mmol) followed by (4- fluorophenyl)methanesulfonyl chloride (16 mg, 0.08 mmol). The reaction was stirred at rt overnight. To the reaction was added a further 1 equiv. of the sulfonyl chloride and stirred for an additional 2 h at rt. To the reaction was then added toluene and MeOH. The crude was concentrated in vacuo and purified by C18 reverse phase Prep-HPLC (CSH column, from 50 - 70% MeCN/10 mM aqueous ammonium formate, pH = 3.8) to provide the title compound (12 mg, 31% yield). LCMS (ESI) [M+H]+= 657.3.
  • 43
  • [ 103360-04-9 ]
  • tert-butyl 1,4-trans-N-[4-[[6-(4-amino-3-fluorophenyl)-8-(difluoromethyl)pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carbamate [ No CAS ]
  • tert-butyl 1,4-trans-N-[4-[[8-(difluoromethyl)-6-[3-fluoro-4-[(4-fluorophenyl)methylsulfonylamino]phenyl]pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% With pyridine at 20℃; 30.5 tert-Butyl 1,4-trans-N-[4-[[8-(difluoromethyl)-6-[3-fluoro-4-[(4-fluoro- phenyl)methylsulfonylamino]phenyl]pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carba- mate To a suspension of tert-butyl 1,4-trans-N-[4-[[6-(4-amino-3-fluoro-phenyl)-8- (difluoromethyl)pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carbamate (135 mg, 0.27 mmol) in pyridine (1 mL) was added (4-fluorophenyl)methanesulfonyl chloride (67 mg, 0.32 mmol). The reaction wass stirred at rt overnight then another portion of (4-fluorophenyl)me- thanesulfonyl chloride (56 mg, 0.27 mmol) was added and continued stirring at rt. After 2 h, the mixture was diluted with toluene and MeOH and concentrated under reduced pressure. The crude was dissoved in DMSO and purified by prep-HPLC (CSH column, 50 - 70% MeCN/10 mM aqueous ammonium formate, pH = 3.8) to provide the title compound (68 mg, 37% yield). LCMS (ESI) [M+H]+= 675.3.
  • 44
  • [ 103360-04-9 ]
  • tert-butyl N-1,4-trans-[4-[[6-(6-amino-2-methyl-3-pyridyl)-8-(difluoromethyl)pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carbamate [ No CAS ]
  • tert-butyl N-1,4-trans-[4-[[8-(difluoromethyl)-6-[6-[(4-fluorophenyl)methylsulfonylamino]-2-methyl-3-pyridyl]pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
17% With pyridine at 20℃; for 5h; 32.2 Step 2: tert-Butyl N-1,4-trans-[4-[[8-(difluoromethyl)-6-[6-[(4-fluorophenyl)me- thylsulfonylamino]-2-methyl-3-pyridyl]pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]car- bamate tert-Butyl N-1,4-trans- [4-[[6-(6-amino-2-methyl-3-pyridyl)-8-(difluorome- thyl)pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carbamate (102 mg, 0.20 mmol) was sus- pended in pyridine (806 mg, 10.2 mmol) and to the mixture was added (4-fluorophenyl)me- thanesulfonyl chloride (51 mg, 0.25 mmol). The reaction was stirred at rt for 2 h then a fur- ther portion of (4-fluorophenyl)methanesulfonyl chloride (81 mg, 0.40 mmol) was added. Af- ter stirring a further 3 h, diethylamine (100 mL) and DMSO (3 mL) were added and concen- trated to remove pyridine. The crude was purified by prep-HPLC (CSH column, 45 - 65% MeCN/10 mM aqueous ammonium formate, pH = 3.8) to provide the title compound (24 mg, 17% yield). LCMS (ESI) [M+H]+= 672.3.
  • 45
  • [ 103360-04-9 ]
  • tert-butyl N-[(1,4-trans)-4-[[6-(4-amino-3-fluoro-phenyl)-8-(methoxymethyl)pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carbamate [ No CAS ]
  • tert-butyl N-[(1,4-trans)-4-[[6-[3-fluoro-4-[(4-fluorophenyl)methylsulfonylamino]phenyl]-8-(methoxymethyl)pyrido[3,2-d]pyrimidin-2-yl]amino]cyclohexyl]carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
21% With pyridine at 20℃; for 0.5h; 37.4 Step 4: tert-Butyl N-[(1,4-trans)-4-[[6-[3-fluoro-4-[(4-fluorophenyl)methyl- sulfonylamino]phenyl]-8-(methoxymethyl)pyrido[3,2-d]pyrimidin-2-yl]amino]cyclo- hexyl]carbamate A flask was charged with tert-butyl ((1,4-trans)-4-((6-chloro-8-(methoxyme- thyl)pyrido[3,2-d]pyrimidin-2-yl)amino)cyclohexyl)carbamate (100 mg, 0.20 mmol) and pyr- idine (2 mL).4-Fluorophenyl)methanesulfonyl chloride (252 mg, 1.21 mmol) was added and stirred at rt for 30 min. MeOH (1 mL) and toluene (10 mL) were then added and the mixture was concentrated with silica gel and purified by flash chromatography through silica gel (0- 70 % EtOAc/heptanes) to provide the title compound (28 mg, 21% yield). LCMS (ESI) [M+H]+= 669.4.
  • 46
  • [ 103360-04-9 ]
  • tert-butyl (3S,5S)-3-[[6-chloro-8-(difluoromethyl)pyrido[3,2-d]pyrimidin-2-yl]amino]-5-fluoropiperidine-1-carboxylate [ No CAS ]
  • tert-butyl (3S,5S)-3-[[8-(difluoromethyl)-6-[3-fluoro-4-[(4-fluorophenyl)methylsulfonylamino]phenyl]pyrido[3,2-d]pyrimidin-2-yl]amino]-5-fluoro-piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
34% With pyridine In dichloromethane at 20℃; for 1h; 38.3 Step 3: tert-Butyl (3S,5S)-3-[[8-(difluoromethyl)-6-[3-fluoro-4-[(4-fluoro- phenyl)methylsulfonylamino]phenyl]pyrido[3,2-d]pyrimidin-2-yl]amino]-5-fluoro-piperi- dine-1-carboxylate tert-Butyl (3S,5S)-3-[[6-chloro-8-(difluoromethyl)pyrido[3,2-d]pyrimidin-2- yl]amino]-5-fluoro-piperidine-1-carboxylate (76 mg, 0.15 mmol) was dissolved in CH2Cl2 (1 mL) and to the solution was added pyridine (0.5 mL) followed by (4-fluorophenyl)me- thanesulfonyl chloride (313 mg, 1.5 mmol). The reaction was stirred at rt for 1 h. MeOH (1 mL) and toluene (5 mL) were then added and concentrated to dryness. The crude was dis- solved in DMSO and purified by prep-HPLC (CSH column, 50-70% MeCN/10 mM aqueous ammonium formate, pH = 3.8) to provide the title compound (35 mg, 34% yield). LCMS (ESI) [M+H]+ = 679.3.
  • 47
  • [ 103360-04-9 ]
  • tert-butyl ((1,4-trans)-4-((6-(4-amino-2,3,5-trifluorophenyl)-8-methylpyrido[3,2-d]pyrimidin-2-yl)amino)cyclohexyl)carbamate [ No CAS ]
  • tert-butyl ((1,4-trans)-4-((8-methyl-6-(2,3,5-trifluoro-4-((4-fluorophenyl)methylsulfonamido)phenyl)pyrido[3,2-d]pyrimidin-2-yl)amino)cyclohexyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% Stage #1: 4-fluorobenzylsulfonyl chloride; tert-butyl ((1,4-trans)-4-((6-(4-amino-2,3,5-trifluorophenyl)-8-methylpyrido[3,2-d]pyrimidin-2-yl)amino)cyclohexyl)carbamate With pyridine at 20℃; Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; 52.3 Step 3: tert-Butyl ((1,4-trans)-4-((8-methyl-6-(2,3,5-trifluoro-4-((4-fluoro- phenyl)methylsulfonamido)phenyl)pyrido[3,2-d]pyrimidin-2-yl)amino)cyclohexyl)carbamate A mixture of tert-butyl ((1,4-trans)-4-((6-(4-amino-2,3,5-trifluorophenyl)-8- methylpyrido[3,2-d]pyrimidin-2-yl)amino)cyclohexyl)carbamate (75 mg, 0.15 mmol) and (4- fluorophenyl)methanesulfonyl chloride (125 mg, 0.60 mmol), in pyridine (1.0 mL), was stirred overnight at rt to provide a mixture of the desired sulfonamide as well as undesired bis-sulfonamide. Pyridine was evaporated under reduced pressure and the residue was dis- solved in THF (2 mL) and treated with a 1M tetrabutylammonium fluoride in THF (0.15 mL, 0.15 mmol) and stirred at rt until most of the bis-sulfonamide converted to desired mono-sul- fonamide. THF was evaporated under reduced pressure and the compound was purified by flash chromatography through silica gel (0 - 20% EtOAc/CH2Cl2) to provide the title com- pound (56 mg, 56% yield). LCMS (ESI) [M+H]+ = 675.4.
  • 48
  • (3-amino-2,6-difluorophenyl)[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]methanone [ No CAS ]
  • [ 103360-04-9 ]
  • N-(3-(5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl)-1-(4-fluorophenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
31% With pyridine at 60℃; 4.3. Synthesis of the sulfonamides (general procedure B) General procedure: To a solution of the corresponding aniline (81 or 83) (1.0 eq.) andpyridine (1 M), the appropriate sulfonyl chloride was added dropwise(1.1 eq). The resulting mixture was stirred at 60 C until TLCrevealed complete consumption of the starting material (3e12 h).After cooling to RT, the crude was diluted with EtOAc, and thenwashed with aqueous 1M HCl solution. The organic layer was driedover sodium sulfate, and the solvent was evaporated. All productswere isolated applying flash chromatography.
  • 49
  • S-(4-fluorobenzyl)isothiourea [ No CAS ]
  • [ 103360-04-9 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; N-chloro-succinimide In acetonitrile at 20℃; 4.2 Step 2: Preparation of compound 4d At room temperature, N-chlorosuccinimide (26.71 g, 200 mmol) was dissolved in a mixed solution of 2N hydrochloric acid (13.6 mL) and acetonitrile (80 mL), then compound 4c was added, and the mixture was stirred for 1 hour.The mixture was concentrated under reduced pressure, the residue was added with water and cooled, the solid was collected by filtration, the filter cake was added with water and sonicated, and filtered again to obtainThe desired white solid compound 367d (7g, yield 67%), namely (4-fluorophenyl)methanesulfonyl chloride was obtained.
  • 50
  • [ 103360-04-9 ]
  • 4-(4-aminophenyl)-N-(1-methyl-1H-pyrazol-4-yl)pyrimidin-2-amine [ No CAS ]
  • C21H19FN6O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
38.7% With pyridine at 80℃; for 1.5h; 4.3 Step 3: Preparation of compound 4 (TDM-180963) To a solution of compound 4e (600 mg, 2.25 mmol) in pyridine (20 mL) was added compound 4d (940 mg, 4.5 mmol) at room temperature.The mixture was heated to 80°C and stirred for 1.5 hours, then concentrated under reduced pressure, methanol was added to the residue, the solid was collected by filtration, and purified by silica gel chromatography (dichloromethane: 10% methanol in dichloromethane = 30:70) to obtain Yellow solid. The solid was slurried with dichloromethane and methanol, the filter cake was added with dimethyl sulfoxide, concentrated under reduced pressure, then added with water, repeated ultrasonic filtration (3 times), and finally lyophilized to obtain the desired yellow solid compound 4, TDM-180963 (Compound 363, 381.8 mg, yield 38.7%), namely 1-(4-fluorophenyl)-N-(4-(2-(((1-methyl-1H-pyrazol-4-yl)amino )Pyrimidin-4-yl)phenyl)methanesulfonamide.
  • 51
  • [ 103360-04-9 ]
  • 2-(3-fluorophenyl)azepane [ No CAS ]
  • 1-((4-fluorobenzyl)sulfonyl)-2-(3-fluorophenyl)azepane [ No CAS ]
YieldReaction ConditionsOperation in experiment
7% With triethylamine In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere; 4.1.4. general procedure four General procedure: To a solution of selected amine (1 mmol, 1 eq.) and Et3N (1.25 mmol,1.25 eq.) in dry CH2Cl2 (0.2 M) under an atmosphere of N2 at 0 °C was added the sulfonyl chloride (1 mmol, 1 eq.). The reaction was then allowed to warm to room temperature and stirred for 1 h. The reaction was then washed with saturated NaHCO3 (2 × 5 mL), brine (1 × 5 mL),dried with Na2SO4 and the solvent removed in vacuo.
7% With triethylamine In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere; 4.1.4. general procedure four General procedure: To a solution of selected amine (1 mmol, 1 eq.) and Et3N (1.25 mmol,1.25 eq.) in dry CH2Cl2 (0.2 M) under an atmosphere of N2 at 0 °C was added the sulfonyl chloride (1 mmol, 1 eq.). The reaction was then allowed to warm to room temperature and stirred for 1 h. The reaction was then washed with saturated NaHCO3 (2 × 5 mL), brine (1 × 5 mL),dried with Na2SO4 and the solvent removed in vacuo.
  • 52
  • [ 103360-04-9 ]
  • (4-fluorophenyl)methanesulfonohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With hydrazine hydrate monohydrate In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere;
  • 53
  • [ 103360-04-9 ]
  • methyl (3-benzyloxy-5-(1,2,3,6-tetrahydropyridin-4-yl)picolinoyl)glycinate [ No CAS ]
  • methyl (3-benzyloxy-5-(1-((4-fluorobenzyl)sulfonyl)-1,2,3,6-tetrahydropyridin-4-yl)picolinoyl)glycinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
66.1% With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 8h; Inert atmosphere; 4.1.13. General procedure for the preparation of 28a-g, 28i-n, and 30a-f General procedure: To a solution of 27c (100 mg, 0.26 mmol) in DCM (5 mL) was addedcorresponding arylsulfonyl chlorides (0.52 mmol), and DIPEA (95 μL,0.57 mmol). The mixture was stirred at room temperature for 8 h undera nitrogen atmosphere. The resulting mixture was quenched with saturatedNaHCO3 solution (10 mL) and then extracted with DCM (20 mL ×2). The combined organic layers were washed with brine (50 mL), driedover anhydrous Na2SO4, filtered, and concentrated. The residue waspurified by column chromatography (petroleum ether: ethyl acetate =1:3) to give the solid 28a-g, 28i-n, and 30a-f.
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