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CAS No. :51767-39-6 MDL No. :MFCD00720883
Formula : C7H9NO3S Boiling Point : -
Linear Structure Formula :- InChI Key :YJASRJZSSUOGKB-UHFFFAOYSA-N
M.W : 187.22 Pubchem ID :4483147
Synonyms :

Safety of [ 51767-39-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338-P310 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 51767-39-6 ]

* 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 [ 51767-39-6 ]

[ 51767-39-6 ] Synthesis Path-Downstream   1~76

  • 1
  • [ 51767-39-6 ]
  • [ 73021-84-8 ]
YieldReaction ConditionsOperation in experiment
91.5% With manganese(IV) oxide; acetic acid at 25℃; for 1h; 3 Synthesis of p-quinone monomethanesulfonimide by oxidation of p-methanesulfonamidophenol with MnO2 OR A mixture containing 30 g (0.160 mol) of p-methanesulfonamidophenol, 18 g (1.1 eq.) of activated 85% MnO2 and 450 ml (15 vol.) of acetic acid is stirred at 25+-5° C. for 1 hour, and the insoluble matter is then filtered off and washed with four times 200 ml of acetic acid. The filtration mother liquors and the washing waters are combined and concentrated under vacuum. The residue is taken up in a mixture of 600 ml of dichloromethane and 250 ml of water. The phases are separated by settling, the organic phase is retained and the aqueous phase is re-extracted with 150 ml of dichloromethane. The combined dichloromethane phases are concentrated under vacuum and the solid obtained is taken up in 250 ml of ethanol. The product is filtered off and dried under vacuum. 27.06 g of p-quinone monomethanesulfonimide are obtained. Mass yield: 91.5%. Melting point in accordance with the literature (134° C.). The retention time by HPLC analysis is identical to that of p-quinone monomethanesulfonimide obtained via the method of R. Adams et al.
83% With NaIO4*SiO2 In dichloromethane at 20℃; for 2h; 7 6.1.2. N-(4-Oxocyclohexa-2,5-dien-1-ylidene)naphthalene-2-sulfonamide (4a) General procedure: To a solution of compounds 3a (2.99 g, 10.0 mmol) in 200 mL of CH2Cl2, was added 22 g (15 mmol) of NaIO4/SiO2(0.68 mmol of NaIO4/1 g of SiO2) [18]. After stirring at room temperature for 2 h, the solid particles were filtered from the solution and washed with 20 mL of CH2Cl2, and the filtrates were evaporated in vacuum to obtain reddish-brown crude compound 4a which was then purified by recrystallization using EtOAc.
75% With lead (IV) acetate; acetic acid In ethylene glycol at 20℃; for 1.66667h; 1 Synthesis of N-(4-oxocyclohexa-2,5-dienylidene)methanesulfonamide (5) Example 1 Synthesis of N-(4-oxocyclohexa-2,5-dienylidene)methanesulfonamide (5) To a stirred suspension of 19 g of 4-(methylsulfonylamino)phenol (4, 1 eq., prepared according to ) in 70 ml of glacial acetic acid is added at room temperature 44 g of lead tetraacetate (1.02 eq) in several portions over 15 minutes. The resulting mixture is stirred for 25 minutes. 0.5 ml of ethylene glycol is added and the mixture is stirred for 15 minutes. Then 5 ml of ethylene glycol is added and the stirring is continued for 45 minutes. The mixture is cooled down to 8 °C, the product is filtered off, washed with cold acetic acid and dried to give 14 g of product (75 % yield).
75% With lead (IV) acetate; acetic acid at 20℃; for 0.666667h; 1 To a stirred suspension of 19 g of 4-(methylsulfonylamino)phenol (4, 1 eq., prepared according to J. Med. Chem. 1999, 42, 1041-1052) in 70 ml of glacial acetic acid is added at room temperature 44 g of lead tetraacetate (1.02 eq) in several portions over 15 minutes. The resulting mixture is stirred for 25 minutes. 0.5 ml of ethylene glycol is added and the mixture is stirred for 15 minutes. Then 5 ml of ethylene glycol is added and the stirring is continued for 45 minutes. The mixture is cooled down to 8 °C, the product is filtered off, washed with cold acetic acid and dried to give 14 g of product (75 % yield).
69% With anhydrous silver carbonate In toluene at 20℃; for 0.5h; Inert atmosphere; 4.4.1. General procedure 2 for the synthesis of quinone monoimides using Ag2CO3 on Celite: preparation of compound 11a (R4=SO2Ph) General procedure: To a cold (0 °C) solution of 8a (25 mg, 0.1 mmol) in toluene (5 mL) was added Ag2CO3/Celite (60 mg, 0.1 mmol) in one portion. The resulting mixture was vigorously stirred for 30 min at 0 °C. The reaction mixture was then filtered on a 1 cm thick pad of Celite, washing with toluene. The filtrate was evaporated under reduced pressure to give quinone imide 11a (24.2 mg, 98%) as a yellow solid.
50.2% With manganese(IV) oxide In acetic acid at 35℃; for 1.5h; 2 Synthesis of N-(4-oxocyclohexa-2,5-dien-1-ylidene)methanesulphonamide (IIId) Example 2 Synthesis of N-(4-oxocyclohexa-2,5-dien-1-ylidene)methanesulphonamide (IIId) The sulphonamide (30 g; 0.16 mol; 1 eq) is oxidized in acetic acid (450 ml; 15 V) at 35° C. in the presence of manganese oxide (15.76 g; 0.179 mol; 1.12 eq). After stirring at 35° C. for 1 h 30, the reaction is complete and the medium is evaporated to dryness. The black solid obtained is taken up in dichloromethane (400 ml). The precipitate of manganese salts formed is filtered off and then washed with DCM (400 ml). The black organic phases are subsequently percolated through a bed of Florisil (190 g) in order to give clear liquors orange in colour. After evaporation, an orange solid is obtained (18.5 g) comprising 15% of benzoquinone, which is removed by two operations of suspending in ethanol (20 ml) at 20° C. 14.9 g of a fine orange powder of N-(4-oxocyclohexa-2,5-dien-1-ylidene)methanesulphonamide are obtained. Crude isolated yield of N-(4-oxocyclohexa-2,5-dien-1-ylidene)methanesulphonamide: 62% by weight. Yield after purification: 50.2% by weight. 1H NMR (400 MHz, d6-DMSO): δ 3.41 (s, 3H, -SO2CH3); 6.83 (m, 2H, CH); 7.17 (m, 1H, CH); 7.84 (m, 1H, CH). 13C NMR (d6-DMSO): δ 42.5 (CH3); 129.5, 135.6, 136.0, 139.9 (4*CH); 164.2 (Cq=N); 186.0 (Cq=O).
With lead tetraacetate
With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; for 1h;

  • 2
  • [ 123-30-8 ]
  • [ 124-63-0 ]
  • [ 51767-39-6 ]
YieldReaction ConditionsOperation in experiment
87.2% With hydrogenchloride In methanol; water at 20 - 23℃; for 1.16667h; 1 Synthesis of p-methanesulfonamidophenol (or N-(4-hydroxyphenyOmethanesulfonamide) according to method II Synthesis of p-methanesulfonamidophenol (or N-(4-hydroxyphenyOmethanesulfonamide) according to method II 10 g (91.6 mmol) of p-aminophenol are dissolved in 250 ml of methanol supplemented with 0.5 ml of 36% hydrochloric acid. The mixture is stirred vigorously and 10.6 g (1 eq.) of methanesulfonyl chloride are added at between 20 and 23° C., over 10 minutes. The mixture is maintained for 1 hour at 20-23° C. and is then neutralized very slowly (over 2 hours) to pH 5.5-6 by adding sodium hydrogen carbonate (8.2 g in total). The mixture is maintained for 30 minutes and is then acidified with 5 ml of 36% hydrochloric acid. The salts formed are removed by filtration and the reaction medium is concentrated under vacuum to a residual volume of 35 ml. 100 ml of 1N hydrochloric acid are then added and the mixture is concentrated again to a residual volume of 95 ml in order to remove the residual methanol. The precipitated product (13.3 g, 75.6%) is recovered by filtration and the filtration mother liquors are extracted with 3 times 50 ml of ethyl acetate. Concentrating the ethyl acetate to dryness gives a further 1.9 g (11.6%). Total yield: 87.2% by weight m.p.: 157.1° C. (lit. 154.5-155.5° C.)
81% In methanol for 1h; Ambient temperature;
81% With pyridine In dichloromethane at 0 - 20℃;
70% With sodium hydrogencarbonate In water at 70℃; for 0.5h;
67% With pyridine In methanol at 20℃; for 1.5h; 1 Synthesis of 4-hydroxyphenylmethanesulphonamide (VId) Example 1 Synthesis of 4-hydroxyphenylmethanesulphonamide (VId) 4-Aminophenol (10 g; 0.091 mol; 1 eq) is suspended in methanol (100 ml) in the presence of pyridine (7.67 ml; 0.095 mol; 1.05 eq) at 20° C. Mesyl chloride (7.16 ml; 0.091 mol; 1.05 eq) is slowly run onto the reaction medium, which then turns orange and then pink in colour. The methanol is removed by evaporating to dryness when the reaction is complete (1 h 30). The residue obtained is treated for 30 min with a dilute 1N hydrochloric acid solution (85.5 ml; 1.05 eq). The pink solid formed is filtered off and then washed with 1N HCl (30 ml) before being purified under hot conditions (45° C.) by treatment with active charcoal in ethyl acetate (30 ml). The solid obtained is washed with 1N HCl and then dried overnight at 40° C. in an oven under vacuum. As the aqueous liquors contain a great deal of mesylated product, they are extracted with ethyl acetate. The extraction liquors are treated as above. 10.4 g of sulphonamide, pale pink powder. Isolated yield of 4-hydroxyphenylmethanesulphonamide: 67% by weight. 1H NMR (400 MHz, d6-DMSO): δ 3.41 (s, 3H, -SO2CH3); 6.72 (d, 2H, J=8.5 Hz, CH); 7.02 (d, 2H, J=8.5 Hz, CH); 9.17 and 9.39 (2*s, 2*1H, OH and NH) 13C NMR (d6-DMSO): δ 38.3 (CH3); 115.5 and 124.0 (4*CH); 129.0 (Cq-N); 154.8 (Cq-O)
65% Stage #1: 4-amino-phenol; methanesulfonyl chloride In methanol at 0 - 20℃; for 2h; Stage #2: With hydrogenchloride; water for 1h; I Example I; N-[4-({5-[(4-{(3-fluorophenyl)[(1H-indazol-6-ylamino)carbonyl]amino}-1- piperidinyl)methyl]-6-methyl-2-pyridinyl}oxy)phenyl]methanesulfonamide; The synthesis of intermediate aldehyde 4 The synthesis of intermediate 1 was accomplished as described in the literature [Singh et al., (1991) Synthesis pp.894-896].Preparation of phenol 2 was accomplished as in J. Med. Chem. 1999, 42, 1041. To a stirred 00C suspension of 4-aminophenol (30Og, 2.75 mol) in 3L WIeOH was slowly added methanesulfonyl chloride (106 ml_, 1.37 mol). The reaction mixture was then stirred at room temperature for 2h and evaporated to give a brown solid residue. The residue was stirred vigorously in 3.5 L 1 N HCI for 1h. The solution was filtered to obtain the phenol 2 as an off-white solid, which was washed with ice-cold water and dried in vacuo over NaOH pellets. Yield obtained was 65% (166.2g). 1H NWIR of intermediate 2 MHz, DMSO-d6) δ 9.36 (s, 1 H), 9.17 (s, 1 H), 6.99 - 7.06 (m, 2 H), 6.70 - 6.75 (m, 2 H), 2.84 (s, 3 H). LRMS: (M-H)" calcd for C7H9NO3S - H, 186; found, 186
65% In methanol at 0 - 20℃; for 2h; 1 The synthesis of intermediate aldehyde 3: s; The synthesis of intermediate 1 was accomplished as described in the literature [Singh et al., (1991) Synthesis pp894-896].Preparation of phenol 4 was accomplished as in J. Med. Chem. 1999, 42, 1041 To a stirred 0 °C suspension of 4-aminophenol (30Og, 2.75 mol) in 3L MeOH was slowly added methanesulfonyl chloride (106 mL, 1.37 mol). The reaction mixture was then stirred at room temperature for 2h and evaporated to give a brown solid residue. The residue was stirred vigorously in 3.5 L 1 N HCI for 1h. The solution was filtered to obtain the phenol 4 as an off-white solid, which was washed with ice-cold water and dried in vacuo over NaOH pellets. Yield obtained was 65% (166.2g). 1H NMR of intermediate 4 MHz, DMSO-cfe) d 9.36 (s, 1 H), 9.17 (s, 1 H), 6.99 - 7.06 (m, 2 H), 6.70 - 6.75 (m, 2 H), 2.84 (s, 3 H). LRMS: (M-H)" calcd for C7H9NO3S - H, 186; found, 186
65% In methanol at 0 - 20℃; for 2h; I Preparation of phenol 4 was accomplished as in J. Med. Chew. 1999, 42, 1041. To a stirred 0 °C suspension of 4-aminophenol (30Og, 2.75 mol) in 3L WIeOH was slowly added methanesulfonyl chloride (106 mL, 1.37 mol). The reaction mixture was then stirred at room temperature for 2h and evaporated to give a brown solid residue. The residue was stirred vigorously in 3.5 L 1N HCI for 1h. The solution was filtered to obtain the phenol 4 as an off-white solid, which was washed with ice-cold water and dried in vacuo over NaOH pellets. Yield obtained was 65% (166.2g). 1H NMR of intermediate 4 MHz, DWISO-Cf6) δ 9.36 (s, 1 H), 9.17 (s, 1 H), 6.99 - 7.06 (m, 2 H), 6.70 - 6.75 (m, 2 H), 2.84 (s, 3 H). LRMS: (M-H)" calcd for C7H9NO3S - H, 186; found, 186
48% With pyridine In N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere; 4.2.1. General procedure 1. Sulfonylation of para-aminophenol: preparation of N-(4-hydroxyphenyl)-benzenesulfonamide 8a (R4=SO2Ph) General procedure: To a cooled (0 °C) solution of para-aminophenol (10,9 g, 100 mmol) in DMF (20 mL) was added pyridine (20 mL) and then dropwise (over a 10 min period) benzenesulfonyl chloride (12,8 mL, 100 mmol). The mixture was allowed to warm to rt and was stirred for one additional hour. After this time, water (150 mL) and EtOAc (100 mL) were added. After decantation, the aqueous phase was extracted with EtOAc (100 mL). The combined organic phases were washed with water (150 mL), 5% w/w aqueous solution of copper sulfate (150 mL) and brine (150 mL), dried over Na2SO4 and filtered. After removal of the solvent under reduced pressure, the crude product was purified by flash chromatography (cyclohexane/EtOAc 60:40) to afford compound 8a (19.22 g, 77%) as a white solid.
28.6% In methanol at 10 - 20℃; for 2h; 47.1 Synthesis of N-(4-hydroxyphenyl)methanesulfonamide (295) To a cold suspension of 4-aminophenol (5.45 g, 49.9 mmol) in MeOH (62 ml), methanesulfonyl chloride (1.95 ml, 25.2 mmol) was added under stirring maintaining the temperature between 10 and 15° C. The resulting solution was allowed to warm to RT and stirred for 2 hours. The solvent was removed under vacuum, and the residue was suspended in HCl 1N (62 ml); the insoluble was collected by filtration, washed with water, dried and purified by filtration through a silica gel pad (DCM:MeOH=100:15) affording N-(4-hydroxyphenyl)methanesulfonamide as a brown solid (1.35 g, 7.21 mmol, 28.6% yield).
28.6% In methanol at 10 - 20℃; for 2h; 47.1 Step 1: Synthesis of N-(4-hydroxyphenyl)methanesulfonamide (295) To a cold suspension of 4-aminophenol (5.45 g, 49.9 mmol) in MeOH (62 ml), methanesulfonyl chloride (1.95 ml, 25.2 mmol) was added under stirring maintaining the temperature between 10 and 15°C. The resulting solution was allowed to warm to RT and stirred for 2h. The solvent was removed under vacuum and the residue was suspended in HC1 IN (62 ml); the insoluble was collected by filtration, washed with water, dried and purified by filtration through a silica gel pad (DCM : MeOH = 100 : 15) affording N-(4-hydroxyphenyl)methanesulfonamide as a brown solid (1.35 g, 7.21 mmol, 28.6% yield).
With sodium hydrogencarbonate In acetonitrile at 70℃; for 4h;

Reference: [1]Current Patent Assignee: SANOFI - US2014/18553, 2014, A1 Location in patent: Paragraph 0221-0224
[2]Belayev, Alexander; Zhang, Xuemei; Augustyns, Koen; Lambeir, Anne-Marie; Meester, Ingrid De; et al. [Journal of Medicinal Chemistry, 1999, vol. 42, # 6, p. 1041 - 1052]
[3]Wang; Guziec Jr. [Journal of Organic Chemistry, 2001, vol. 66, # 25, p. 8293 - 8296]
[4]Location in patent: experimental part Avdeenko; Konovalova; Mikhailichenko; Shelyazhenko; Pirozhenko; Yagupol'skii [Russian Journal of Organic Chemistry, 2011, vol. 47, # 4, p. 510 - 519]
[5]Current Patent Assignee: SANOFI - US2013/12729, 2013, A1 Location in patent: Paragraph 0224-0228
[6]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2009/58924, 2009, A1 Location in patent: Page/Page column 11-12
[7]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2009/58919, 2009, A1 Location in patent: Page/Page column 13
[8]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2009/58921, 2009, A1 Location in patent: Page/Page column 13
[9]Location in patent: experimental part Baragona, Fabien; Lomberget, Thierry; Duchamp, Christian; Henriques, Natali; Lo Piccolo, Eugenio; Diana, Patrizia; Montalbano, Alessandra; Barret, Roland [Tetrahedron, 2011, vol. 67, # 45, p. 8731 - 8739]
[10]Current Patent Assignee: Valline SRL - US2013/79313, 2013, A1 Location in patent: Paragraph 0980
[11]Current Patent Assignee: Valline SRL - WO2013/45280, 2013, A1 Location in patent: Page/Page column 252; 253
[12]Adams; Locker [Journal of the American Chemical Society, 1951, vol. 73, p. 1145,1148] Koszowa [Zhurnal Obshchei Khimii, 1953, vol. 23, p. 610;engl.Ausg.S.635]
[13]Zheng, Youguang; Zheng, Ming; Liu, Yi; Xue, Yunsheng; Zhang, Ling; An, Lin; Liu, Ling; Ji, Min [Medicinal Chemistry, 2013, vol. 9, # 3, p. 340 - 350]
[14]Qu, Menghua; Liu, Zhihao; Zhao, Dan; Wang, Changyuan; Zhang, Jianbin; Tang, Zeyao; Liu, Kexin; Shu, Xiaohong; Yuan, Hong; Ma, Xiaodong [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 15, p. 3989 - 3996]
  • 3
  • [ 51767-39-6 ]
  • [ 41978-69-2 ]
  • [ 71269-93-7 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In 1,2-dimethoxyethane Heating;
  • 4
  • [ 1207-69-8 ]
  • [ 51767-39-6 ]
  • [ 137265-11-3 ]
YieldReaction ConditionsOperation in experiment
67% With potassium carbonate In acetone at 150℃; for 28h;
  • 5
  • [ 116-17-6 ]
  • [ 73021-84-8 ]
  • [ 51767-39-6 ]
  • N-(4-Hydroxy-phenyl)-N-isopropyl-methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 10% 2: 85% In benzene for 4h; Ambient temperature;
  • 6
  • [ 73021-84-8 ]
  • [ 51767-39-6 ]
YieldReaction ConditionsOperation in experiment
95% With Diethyl phosphonate In benzene for 16h; Heating;
With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate In chloroform at 25℃;
With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate In chloroform at 25℃;
With substituted hydrazine for 12h; General procedure: a. To a solution of2 mmol of quinone imine 1-1 in 10 mL of ethanol or acetonitrile, glacial acetic acid, a mixture of acetic acid with chloroform was added dropwise a solution of 4 mmol of hydrazine 2-2c in appropriate solvent atroom temperature or at the boiling point of the solvent (1, 1b, 1d-1h, 1j, 1k, 1m, 1n, and 1), or at coolingto -10°C (1-1c, 1h, 1i, 1k, 1l, 1n, and 1o). The reaction mixture was stirred for 12 h, the separatedprecipitate of compounds 3-3 was filtered off.When the precipitate did not form, the solution waspoured on ice or the solvent was partially evaporatedin a vacuum. The product was recrystallized fromethanol, or from benzene-hexane mixture, 1 : 2, orfrom acetic acid.

  • 7
  • [ 73021-84-8 ]
  • [ 868-85-9 ]
  • [ 51767-39-6 ]
  • dimethyl <2-hydroxy-5-((methylsulfonyl)amino)phenyl>phosphonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 40% 2: 60% In benzene for 16h; Heating;
  • 8
  • [ 73021-84-8 ]
  • [ 122-52-1 ]
  • [ 10406-66-3 ]
  • [ 51767-39-6 ]
  • N-(4-Ethoxy-phenyl)-N-ethyl-methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 35% 2: 10% 3: 60% In benzene for 4h; Ambient temperature;
  • 9
  • [ 73021-84-8 ]
  • [ 108-95-2 ]
  • [ 51767-39-6 ]
  • [ 76960-34-4 ]
YieldReaction ConditionsOperation in experiment
88% In tetrahydrofuran for 10h; Ambient temperature;
  • 10
  • [ 51767-39-6 ]
  • [ 222610-51-7 ]
YieldReaction ConditionsOperation in experiment
60% With triethylamine; phosphorus trichloride In chloroform; N,N-dimethyl-formamide at 0 - 20℃;
  • 11
  • [ 7653-68-1 ]
  • [ 107-10-8 ]
  • [ 876-08-4 ]
  • [ 51767-39-6 ]
  • 4-[5-(4-methanesulfonylamino-phenoxy)-[1,3,4]thiadiazole-2-sulfonylmethyl]-<i>N</i>-propyl-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multistep reaction;
  • 12
  • [ 7653-68-1 ]
  • [ 876-08-4 ]
  • [ 452-69-7 ]
  • [ 51767-39-6 ]
  • <i>N</i>-(4-fluoro-3-methyl-phenyl)-4-[5-(4-methanesulfonylamino-phenoxy)-[1,3,4]thiadiazole-2-sulfonylmethyl]-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multistep reaction;
  • 13
  • [ 7653-68-1 ]
  • [ 876-08-4 ]
  • [ 51767-39-6 ]
  • 4-[5-(4-methanesulfonylamino-phenoxy)-[1,3,4]thiadiazole-2-sulfonylmethyl]-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multistep reaction;
  • 14
  • [ 7653-68-1 ]
  • [ 876-08-4 ]
  • [ 51767-39-6 ]
  • [ 100-46-9 ]
  • <i>N</i>-benzyl-4-[5-(4-methanesulfonylamino-phenoxy)-[1,3,4]thiadiazole-2-sulfonylmethyl]-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multistep reaction;
  • 15
  • CH3SO2Cl [ No CAS ]
  • [ 123-30-8 ]
  • [ 51767-39-6 ]
YieldReaction ConditionsOperation in experiment
13.6 g (81%) In hydrogenchloride; sodium hydroxide 1 Synthesis of a Series of Protected and Unprotected Prolylpyrrolidine Diaryl Phosphonates 4-Methylsulfonylaminophenol (8f). To a suspension of 4-aminophenol (200 mmol, 21.8 g) in MeOH (250 mL), CH3SO2Cl (100 mmol, 7.75 mL) was added at 10-15° C. with stirring. The resulting solution was stirred for 1 h at room temperature and evaporated. The residue was suspended in 1N HCl (250 mL), the solid was filtered, washed with water and dried in vacuum over NaOH. Yield 13.6 g (81%): mp 165-166° C.; 1H-NMR (DMSO) δ (ppm) 2.85 (s, 3H, CH3S), 6.70 (d, 2Harom), 7.10 (d, 2Harom), 8.70 (s, 1H, OH), 8.85 (s, 1H, NH).
  • 16
  • N-[4-(Benzyloxy)phenyl]methanesulfonamide [ No CAS ]
  • [ 51767-39-6 ]
YieldReaction ConditionsOperation in experiment
In ethanol E.B Step B. Step B. N-(4-Hydroxyphenyl)methanesulfonamide N-[4-(Benzyloxy)phenyl]methanesulfonamide (3.0 g, 10.8 mmol) was dissolved in ethanol (150 mL). 10% Palladium on carbon (0.3 g) was added and the mixture shaken overnight under 50 psi hydrogen on a Parr apparatus. The solution was filtered through a Celite pad and the solvent removed to yield the title compound (1.32 g, 7.4 mmol). 1H NMR (DMSO-d6, 300 MHz): d 2.84 (s, 3H), 6.76 (d, 2H), 7.05 (d, 2H), 9.20 (s, 1H), 9.41 (s, 1H)
  • 17
  • [ 7664-41-7 ]
  • [ 124-63-0 ]
  • [ 51-72-9 ]
  • [ 51767-39-6 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; N-ethyl-N,N-diisopropylamine; In pyridine; (47a) 77 ml of methanesulfonic acid chloride are added dropwise in the course of about 30 minutes, with ice-cooling and stirring, to a solution of 103.7 g of 4-methylaminophenol sulfate in 330 ml of pyridine and 102 ml of N,N-diisopropylethylamine, and the mixture is stirred overnight at room temperature. The volatile constituents are evaporated off, and the residue is distributed between ethyl acetate and water; the organic phase is subsequently separated and concentrated by evaporation, and the crystalline residue is heated with 300 ml of 6N sodium hydroxide solution on a water-bath until completely dissolved. The solution is filtered, and the pH-value is adjusted to 2 with concentrated hydrochloric acid, whereupon 4-(N-methylsulfonylamino)-phenol precipitates in crystalline form. It is filtered off with suction and dried in vacuo at 80, m.p. 135-136.
  • 18
  • [ 51767-39-6 ]
  • [ 24993-81-5 ]
  • 4-(methanesulfonamido)phenyl 4-(2-bromoethyl)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In ethanol; dichloromethane 1.4.a (a) (a) Synthesis of 4-(Methanesulfonamido)phenyl 4-(2-bromoethyl)benzoate To a mixture of 6.05 g (0.0323 mol) of N-(4-hydroxylphenyl)methane sulfonamide, 3.27 g (0.0323 mol) of triethylamine and 100 ml of methylene chloride was added a solution of 8.0 g (0.0323 mol) of p-(2-bromoethyl)benzoyl chloride in 75 mL of methylene chloride dropwise. The reaction mixture was stirred for 4 hours at room temperature. The resultant solution was washed with 2% hydrochloric acid and twice with water, dried over magnesium sulfate and concentrated on a rotary evaporator to a white solid. Recrystallization from 700 ml of 1:1 ethanol:water gave 10.75 g (83.5% of theory) of 4-(methanesulfonamido)phenyl 4-(2-bromoethyl)benzoate; mp=161°-2° C. Analysis calculated for C16 H16 BrNO4 S: C, 48.3; H, 4.0; Br, 20.1; N, 3.5; S, 8.1. Found: C, 48.4; H, 4.3; Br, 20.6; N, 3.7; S, 7.6.
  • 19
  • [ 51767-39-6 ]
  • [ 66909-36-2 ]
  • [ 1150100-29-0 ]
YieldReaction ConditionsOperation in experiment
93% With caesium carbonate In N,N-dimethyl-formamide at 80℃; I Solution of chloropyridine 1 (25g, 0.16 mol), phenol 2 (33.7g, 0.18 mol), and Cs2CO3 (106.8g, 0.33 mol) in dry DMF (350 mL) was stirred at 80 0C overnight. The reaction mixture was then filtered and rinsed with CH2CI2. The filtrate was concentrated to a residue by rotary evaporation, and then diluted with water. The pH was adjusted to 7 by the addition of 2M aqueous HCI and then extracted with CH2CI2. The organic extracts were pooled, dried (Na2SO4), filtered and evaporated to provide a dark brown solid. To this was added 200 mL Et2O, and the solution was stirred overnight and then filtered. The light brown solid was washed with a small amount of Et2O, and dried to provide intermediate 3 as a light brown solid (46.3g, 93%). 1H NMR of 3 (400 MHz, DMSO-Cf6) δ 9.77 (br. s., 1 H), 8.20 (d, J=8.43 Hz, 1 H), 7.20 - 7.26 (m, 2 H), 7.12 - 7.17 (m, 2 H), 6.95 (d, J=8.07 Hz, 1 H), 2.98 (s, 3 H), 2.48 (s, 3 H). LRMS: (M+H)+ calcd for C14H13N3O3S + H, 304; found, 304.
93% Stage #1: 4-(methylsulfonylamino)phenol; 6-chloro-2-methyl-3-pyridinecarbonitrile With caesium carbonate In N,N-dimethyl-formamide at 80℃; Stage #2: With hydrogenchloride In water 1 Solution of chloropyridine 1 (25g, 0.16 mol), phenol 4 (33.7g, 0.18 mol), and Cs2CO3 (106.8g, 0.33 mol) in dry DMF (350 mL) was stirred at 80 °C overnight. The reaction mixture was then filtered and rinsed with CH2CI2. The filtrate was concentrated to a residue by rotary evaporation, and then diluted with water. The pH was adjusted to 7 by the addition of 2M aqueous HCI and then extracted with CH2CI2. The organic extracts were pooled, dried (Na2SO,)), filtered and evaporated to provide a dark brown solid. To this was added 200 mL Et2O, and the solution was stirred overnight and then filtered. The light brown solid was washed with a small amount of Et2O, and dried to provide intermediate 2 as a light brown solid (46.3g, 93%). 1H NMR of 2 (400 MHz, DMSO-d6) δ 9.77 (br. s., 1 H), 8.20 (d, J=8.43 Hz, 1 H), 7.20 - 7.26 (m, 2 H), 7.12 - 7.17 (m, 2 H), 6.95 (d, J=8.07 Hz, 1 H), 2.98 (s, 3 H), 2.48 (s, 3 H). LRMS: (M+H)+ calcd for C14Hi3N3O3S + H, 304; found, 304.
93% Stage #1: 4-(methylsulfonylamino)phenol; 6-chloro-2-methyl-3-pyridinecarbonitrile With caesium carbonate In N,N-dimethyl-formamide at 80℃; Stage #2: With hydrogenchloride In water I Solution of chloropyridine 3 (25g, 0.16 mol), phenol 4 (33.7g, 0.18 mol), and Cs2CO3 (106.8g, 0.33 mol) in dry DWIF (350 mL) was stirred at 80 °C overnight. The reaction mixture was then filtered and rinsed with CH2CI2. The filtrate was concentrated to a residue by rotary evaporation, and then diluted with water. The pH was adjusted to 7 by the addition of 2M aqueous HCI and then extracted with CH2CI2. The organic extracts were pooled, dried (Na2SO4), filtered and evaporated to provide a dark brown solid. To this was added 200 mL Et2O, and the solution was stirred overnight and then filtered. The light brown solid was washed with a small amount of Et2O, and dried to provide intermediate 5 as a light brown solid (46.3g, 93%). 1H NWIR of 5 (400 MHz, DMSO-Cf6) δ 9.77 (br. s., 1 H), 8.20 (d, J=8.43 Hz, 1 H), 7.20 - 7.26 (m, 2 H), 7.12 - 7.17 (m, 2 H), 6.95 (d, J=8.07 Hz, 1 H), 2.98 (s, 3 H), 2.48 (s, 3 H). LRMS: (M+H)* calcd for C14H13N3O3S + H, 304; found, 304.
With caesium carbonate In N,N-dimethyl-formamide at 80℃;

  • 20
  • 2-chloro-5-cyanopyridine 1-oxide [ No CAS ]
  • [ 51767-39-6 ]
  • [ 1150100-92-7 ]
YieldReaction ConditionsOperation in experiment
90% With caesium carbonate In N,N-dimethyl-formamide at 45℃; for 4h; 17 To a solution of intermediate 72 (616 mg, 4 mmol) in DMF (25mL) were added intermediate 4 (748 mg, 4 mmol) and Cs2CO3 (1 ,3 g, 4 mmol). The mixture was stirred for 4 hours at 45 0C before cooled down to room temperature and diluted with water. Intermediate 73 was precipitated and collected as white solid by filtration (1.1 g, 90%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.8 (s, 1 H), 9.0 (s, 1 H), 7.7 (s, 1 H), 7.2 (m, 2 H), 7.1 (d, J=8.8 Hz, 2 H), 3.0 (s, 3 H). MS m/z 306 (M+H)*.
90% With caesium carbonate In N,N-dimethyl-formamide at 45℃; for 4h; To a solution of intermediate 32 (616 mg, 4 mmol) in DMF (25mL) were added intermediate 4 (748 mg, 4 mmol) and Cs2CO3 (1 ,3 g, 4 mmol). The mixture was stirred for 4 hours at 45 0C before cooled down to room temperature and diluted with water. Intermediate 33 was precipitated and collected as white solid by filtration (1.1 g, 90%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.8 (s, 1 H), 9.0 (s, 1 H), 7.7 (s, 1 H), 7.2 (m, 2 H), 7.1 (d, J=8.8 Hz, 2 H), 3.0 (s, 3 H). MS m/z 306 (M+Hf.
90% With caesium carbonate In N,N-dimethyl-formamide at 45℃; for 4h;
  • 21
  • [ 51767-39-6 ]
  • [ 188781-08-0 ]
  • [ 1150103-17-5 ]
YieldReaction ConditionsOperation in experiment
66% With caesium carbonate In N,N-dimethyl-formamide at 80℃; VIII Intermediate 24; Ethyl 4-methyl-2-({4-[(methylsulfonyl)amiϖo]pheϖyl}oxy)-5-pyrimidinecarboxylate; A mixture of Ethyl^-Chloro^-methyl-S-pyrimidinecarboxylate 23 (930 mg, 4.65 mmol), phenol 4 (870 mg, 4.65 mmol), and Cs2CO3 (2.27 g, 7.0 mmol) in dry DMF (20 mL) was stirred at 80 0C under N2 overnight. The reaction mixture was then filtered and rinsed with CH2CI2. The filtrate was concentrated to a residue by rotary evaporation, and then diluted with water. It was extracted with 10 % MeOH in CH2CI2. The organic extracts were dried over Na2SO4, filtered and evaporated. The residue was purified by ISCO FC with 0-50 % EtOAC in hexane to provide ethyl 4- methyl-2-({4 [(methylsulfonyl)amino]phenyl}oxy)-5-pyrimidinecarboxylate 24 as a white solid (1.07 g, 66 %).1H NMR (CDCI3, 400 MHz) δ 1.4 (t, J=7.1 Hz, 3 H) 2.8 (s, 3 H) 3.0 (s, 3 H) 4.4 (q, J=7.1 Hz, 2 H) 6.5 (s, 1 H) 7.2 (m, 2 H) 7.3 (m, 2 H) 9.0 (s, 1 H). LCMS: (M+H)+ calcd for C15H17N3O5S + H, 352; found, 352.
66% With caesium carbonate In N,N-dimethyl-formamide at 80℃;
  • 22
  • [ 1150103-22-2 ]
  • [ 51767-39-6 ]
  • [ 1150103-23-3 ]
YieldReaction ConditionsOperation in experiment
47% With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 1.5h; IX Intermediate 30; N-{4-[(5-cyano-6-ethyl-2-pyridinyl)oxy]phenyl}methanesulfonamide; A mixture of e-chloro^-ethyl-S-pyridinecarbontrile 29 (223 mg, 1.34 mmol, 1.0 eq.), λ/-(4-hydroxyphenyl)methanesulfonamide 4 (250 mg, 1.34 mmol, 1.0 eq.), and cesium carbonate (545 mg, 1.67 mmol, 1.25 eq.) in dimethyl formamide (3 ml.) was heated at 80 °C for 1.5 hrs. under nitrogen. The reaction mixture was evaporated in vacuo and partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was back-extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, * filtered and evaporated in vacuo. The crude product was purified on flash grade silica gel eluting with 40 % ethyl acetate in hexanes to provide N -{4-[(5-cyano-6- ethyl-2-pyridinyl)oxy]phenyl}methanesulfonamide 30 as a foam (200 mg, 47%). 1H NMR (400 MHz, CDCI3) δ 7.84 (d, J = 8.5 Hz, 1 H), 7.27 (d, J = 9.0 Hz, 2 H), 7.16 (d, J = 8.9 Hz, 2 H), 6.78 (d, J = 8.5 Hz, 1 H), 6.32 (br, 1 H), 3.04 (s, 3 H)1 2.91 (q, J = 7.6 Hz, 2 H), 1.22 (t, J = 7.4 Hz, 3 H); MS m/z 318 (M+H)+.
  • 24
  • [ 51767-39-6 ]
  • [ 1150100-30-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: caesium carbonate / N,N-dimethyl-formamide / 80 °C 2: diisobutylaluminium hydride / dichloromethane / 0 °C
  • 25
  • [ 51767-39-6 ]
  • [ 1150102-95-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: caesium carbonate / N,N-dimethyl-formamide / 80 °C 2: diisobutylaluminium hydride / dichloromethane / 0 °C 3: sodium tris(acetoxy)borohydride; triethylamine / dichloromethane / 20 °C
  • 26
  • [ 51767-39-6 ]
  • [ 1150103-18-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: caesium carbonate / N,N-dimethyl-formamide / 80 °C 2: diisobutylaluminium hydride / dichloromethane / -78 - 0 °C
  • 27
  • [ 51767-39-6 ]
  • [ 1150103-19-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: caesium carbonate / N,N-dimethyl-formamide / 80 °C 2: diisobutylaluminium hydride / dichloromethane / -78 - 0 °C 3: manganese(IV) oxide / dichloromethane / 20 °C
  • 28
  • [ 51767-39-6 ]
  • [ 1150103-00-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: caesium carbonate / N,N-dimethyl-formamide / 80 °C 2: diisobutylaluminium hydride / dichloromethane / -78 - 0 °C 3: manganese(IV) oxide / dichloromethane / 20 °C 4: sodium tris(acetoxy)borohydride; triethylamine / dichloromethane / 20 °C
  • 29
  • [ 51767-39-6 ]
  • C31H31N7O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: caesium carbonate / N,N-dimethyl-formamide / 80 °C 2: diisobutylaluminium hydride / dichloromethane / 0 °C 3: sodium tris(acetoxy)borohydride; triethylamine / dichloromethane / 20 °C
  • 30
  • [ 51767-39-6 ]
  • C31H33N7O5S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: caesium carbonate / N,N-dimethyl-formamide / 80 °C 2: diisobutylaluminium hydride / dichloromethane / 0 °C 3: sodium tris(acetoxy)borohydride; triethylamine / dichloromethane / 20 °C
  • 31
  • [ 51767-39-6 ]
  • [ 1344734-73-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: caesium carbonate / N,N-dimethyl-formamide / 80 °C 2: diisobutylaluminium hydride / dichloromethane / 0 °C 3: sodium tris(acetoxy)borohydride; triethylamine / dichloromethane / 20 °C
  • 32
  • [ 51767-39-6 ]
  • [ 1344734-74-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: caesium carbonate / N,N-dimethyl-formamide / 80 °C 2: diisobutylaluminium hydride / dichloromethane / 0 °C 3: sodium tris(acetoxy)borohydride; triethylamine / dichloromethane / 20 °C
  • 33
  • [ 51767-39-6 ]
  • [ 1344734-75-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: caesium carbonate / N,N-dimethyl-formamide / 80 °C 2: diisobutylaluminium hydride / dichloromethane / 0 °C 3: sodium tris(acetoxy)borohydride; triethylamine / dichloromethane / 20 °C
  • 34
  • [ 51767-39-6 ]
  • C13H12N2O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: caesium carbonate / N,N-dimethyl-formamide / 80 °C 2: diisobutylaluminium hydride / dichloromethane / 0 °C
  • 35
  • [ 51767-39-6 ]
  • [ 1343489-28-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: silver carbonate / toluene / 0.5 h / 20 °C / Inert atmosphere 2: ethanol / 0.25 h / 0 °C / Inert atmosphere
  • 36
  • [ 51767-39-6 ]
  • [ 141626-36-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: lead(IV) tetraacetate; acetic acid / ethylene glycol / 1.67 h / 20 °C 2: acetic acid / N,N-dimethyl-formamide / 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: lead(IV) tetraacetate; acetic acid / ethylene glycol / 1.67 h / 20 °C 2: trityl perchlorate / dichloromethane / 45 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: lead(IV) tetraacetate; acetic acid / ethylene glycol / 1.67 h / 20 °C 2: sodium methylate / 1,4-dioxane / 1 h / 20 °C
Multi-step reaction with 5 steps 1.1: lead(IV) tetraacetate; acetic acid / ethylene glycol / 1.67 h / 20 °C 2.1: sodium methylate / 1,4-dioxane / 1 h / 20 °C 2.2: Reflux 3.1: water; lithium hydroxide / 1,4-dioxane / 16 h 4.1: 0 °C / Inert atmosphere; Reflux 5.1: sodium carbonate; sodium dodecyl-sulfate / palladium dichloride / water; acetone / 60 °C
Multi-step reaction with 5 steps 1.1: lead(IV) tetraacetate; acetic acid / ethylene glycol / 1.67 h / 20 °C 2.1: sodium methylate / 1,4-dioxane / 1 h / 20 °C 2.2: Reflux 3.1: water; lithium hydroxide / 1,4-dioxane / 16 h 4.1: 0 °C / Inert atmosphere; Reflux 5.1: diisobutylaluminium hydride; magnesium; lithium chloride; diisobutylaluminum chloride / n-heptane; tetrahydrofuran / -10 - 25 °C 5.2: 25 °C
Multi-step reaction with 2 steps 1: lead(IV) tetraacetate; acetic acid / 0.67 h / 20 °C 2: acetic acid / N,N-dimethyl-formamide / 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: lead(IV) tetraacetate; acetic acid / 0.67 h / 20 °C 2: trityl perchlorate / dichloromethane / 45 °C / Inert atmosphere
Multi-step reaction with 3 steps 1.1: lead(IV) tetraacetate; acetic acid / 0.67 h / 20 °C 2.1: sodium methylate / 1,4-dioxane / 1 h / 20 °C 3.1: trifluoroacetic anhydride; phosphoric acid / 20 h / Reflux 3.2: pH 8 / Cooling
Multi-step reaction with 5 steps 1.1: lead(IV) tetraacetate; acetic acid / 0.67 h / 20 °C 2.1: sodium methylate / 1,4-dioxane / 1 h / 20 °C 3.1: water; lithium hydroxide / 1,4-dioxane / 16 h / 20 °C 4.1: thionyl chloride / 0 °C / Inert atmosphere; Reflux 5.1: aluminum (III) chloride / dichloromethane / Reflux 5.2: 25 °C
Multi-step reaction with 5 steps 1.1: lead(IV) tetraacetate; acetic acid / 0.67 h / 20 °C 2.1: sodium methylate / 1,4-dioxane / 1 h / 20 °C 3.1: water; lithium hydroxide / 1,4-dioxane / 16 h / 20 °C 4.1: thionyl chloride / 0 °C / Inert atmosphere; Reflux 5.1: diisobutylaluminium hydride; magnesium; lithium chloride; diisobutylaluminum chloride / n-heptane; tetrahydrofuran / 25 °C / Inert atmosphere 5.2: 0.08 h / -10 - 25 °C 5.3: -30 - 25 °C
Multi-step reaction with 5 steps 1: lead(IV) tetraacetate; acetic acid / 0.67 h / 20 °C 2: sodium methylate / 1,4-dioxane / 1 h / 20 °C 3: water; lithium hydroxide / 1,4-dioxane / 16 h / 20 °C 4: thionyl chloride / 0 °C / Inert atmosphere; Reflux 5: sodium carbonate; sodium dodecyl-sulfate / palladium dichloride / water; acetone / 60 °C
Multi-step reaction with 5 steps 1: manganese(IV) oxide; acetic acid / 1 h / 25 °C 2: sodium methylate / 1,4-dioxane / 0.5 h / 20 °C 3: hydrogenchloride / water; acetone / 5 h / Reflux 4: thionyl chloride / 3.5 h / 20 - 79 °C 5: aluminum (III) chloride / 1,2-dichloro-ethane / 4 h / 0 - 25 °C

  • 37
  • [ 51767-39-6 ]
  • [ 1374967-89-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: lead(IV) tetraacetate; acetic acid / ethylene glycol / 1.67 h / 20 °C 2: acetic acid / N,N-dimethyl-formamide / 20 °C
Multi-step reaction with 2 steps 1: lead(IV) tetraacetate; acetic acid / ethylene glycol / 1.67 h / 20 °C 2: sodium methylate / 1,4-dioxane / 0.5 h / 20 °C
Multi-step reaction with 2 steps 1: lead(IV) tetraacetate; acetic acid / 0.67 h / 20 °C 2: sodium methylate / 1,4-dioxane / 0.5 h / 20 °C
  • 38
  • [ 51767-39-6 ]
  • [ 1329684-19-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: lead(IV) tetraacetate; acetic acid / ethylene glycol / 1.67 h / 20 °C 2.1: sodium methylate / 1,4-dioxane / 1 h / 20 °C 2.2: Reflux
Multi-step reaction with 2 steps 1: lead(IV) tetraacetate; acetic acid / 0.67 h / 20 °C 2: sodium methylate / 1,4-dioxane / 1 h / 20 °C
  • 39
  • [ 51767-39-6 ]
  • [ 1329684-22-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: lead(IV) tetraacetate; acetic acid / ethylene glycol / 1.67 h / 20 °C 2.1: sodium methylate / 1,4-dioxane / 1 h / 20 °C 2.2: Reflux
Multi-step reaction with 2 steps 1: lead(IV) tetraacetate; acetic acid / 0.67 h / 20 °C 2: sodium methylate / 1,4-dioxane / 1 h / 20 °C
Multi-step reaction with 3 steps 1: manganese(IV) oxide; acetic acid / 1 h / 25 °C 2: sodium methylate / 1,4-dioxane / 0.5 h / 20 °C 3: hydrogenchloride / water; acetone / 5 h / Reflux
  • 40
  • [ 51767-39-6 ]
  • [ 1374967-90-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: lead(IV) tetraacetate; acetic acid / ethylene glycol / 1.67 h / 20 °C 2.1: sodium methylate / 1,4-dioxane / 1 h / 20 °C 2.2: Reflux 3.1: water; lithium hydroxide / 1,4-dioxane / 16 h
Multi-step reaction with 3 steps 1: lead(IV) tetraacetate; acetic acid / 0.67 h / 20 °C 2: sodium methylate / 1,4-dioxane / 1 h / 20 °C 3: water; lithium hydroxide / 1,4-dioxane / 16 h / 20 °C
  • 41
  • [ 51767-39-6 ]
  • [ 1329684-25-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: lead(IV) tetraacetate; acetic acid / ethylene glycol / 1.67 h / 20 °C 2.1: sodium methylate / 1,4-dioxane / 1 h / 20 °C 2.2: Reflux 3.1: water; lithium hydroxide / 1,4-dioxane / 16 h 4.1: 0 °C / Inert atmosphere; Reflux
Multi-step reaction with 4 steps 1: lead(IV) tetraacetate; acetic acid / 0.67 h / 20 °C 2: sodium methylate / 1,4-dioxane / 1 h / 20 °C 3: water; lithium hydroxide / 1,4-dioxane / 16 h / 20 °C 4: thionyl chloride / 0 °C / Inert atmosphere; Reflux
Multi-step reaction with 4 steps 1: manganese(IV) oxide; acetic acid / 1 h / 25 °C 2: sodium methylate / 1,4-dioxane / 0.5 h / 20 °C 3: hydrogenchloride / water; acetone / 5 h / Reflux 4: thionyl chloride / 3.5 h / 20 - 79 °C
  • 42
  • [ 51767-39-6 ]
  • [ 1375149-24-8 ]
  • [ 1375149-23-7 ]
  • [ 141626-36-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: lead(IV) tetraacetate; acetic acid / 0.67 h / 20 °C 2: sodium methylate / 1,4-dioxane / 1 h / 20 °C
  • 43
  • [ 51767-39-6 ]
  • 2-(n-butyl)-3-(4-{3-[di(n-butyl)amino]propoxy}benzoyl)-5-(methanesulfonamido)benzofuran hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: lead(IV) tetraacetate; acetic acid / 0.67 h / 20 °C 2.1: triethylamine / 1,4-dioxane / 20 °C 2.2: Reflux
  • 44
  • [ 32315-10-9 ]
  • [ 51767-39-6 ]
  • C9H8Cl3NO5S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide In dichloromethane; water at 0 - 20℃; for 3h;
  • 45
  • [ 35980-24-6 ]
  • [ 51767-39-6 ]
YieldReaction ConditionsOperation in experiment
With methyl propargyl alcohol; potassium <i>tert</i>-butylate In dimethyl sulfoxide at 125℃; for 0.25h; Microwave irradiation;
  • 46
  • [ 51767-39-6 ]
  • [ 1383479-32-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium hydroxide / dichloromethane; water / 3 h / 0 - 20 °C 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 6 h / 20 °C
  • 47
  • [ 1428846-77-8 ]
  • [ 51767-39-6 ]
  • [ 1428848-46-7 ]
YieldReaction ConditionsOperation in experiment
33% With dmap In dichloromethane at 20℃; for 3h; 47.2 Synthesis of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-(methylsulfonamido)phenoxy)carbonyloxy)-ethyl)pyridine 1-oxide (296) To a stirred solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)carbonyloxy)ethyl)pyridine 1-oxide (prepared in an analogous manner to that described in Example 45, Step 4) (0.140 g, 0.239 mmol) in DCM (5 ml), a solution of N-(4-hydroxyphenyl)-methanesulfonamide (0.0672 g, 0.359 mmol) and DMAP (0.0438 g, 0.359 mmol) in DCM (5 ml) was added drop wise, and the reaction was stirred at RT for 3 hours. The solvent was evaporated and the resulting crude was purified by chromatography on silica gel column (DCM:MeOH=10:0.4). A second purification by crystallization from absolute ethanol was required to obtain (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-(methylsulfonamido)-phenoxy)carbonyloxy)ethyl)pyridine 1-oxide as a brown solid (0.050 g, 0.079 mmol, 33% yield, MS/ESI+ 632.74 [MH]+, [αD]=-36.59, c=0.252, DCM).[0982]1H NMR (300 MHz, DMSO-d6) δ ppm 9.78 (s, 1H), 8.59 (s, 2H), 7.17-7.25 (m, 3H), 7.16 (d, 1H), 7.06-7.12 (m, 2H), 7.03 (dd, 1H), 7.09 (t, 1H), 5.90 (dd, 1H), 3.93 (d, 2H), 3.57 (dd, 1H), 3.32 (dd, 1H), 2.98 (s, 3H), 1.12-1.31 (m, 1H), 0.52-0.70 (m, 2H), 0.28-0.46 (m, 2H)
  • 49
  • [ 1428846-77-8 ]
  • [ 51767-39-6 ]
  •  (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-(methylsulfonamido)phenoxy)carbonyloxy)ethyl)pyridine 1-oxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% With dmap In dichloromethane at 20℃; for 3h; 47.2 Step 2: Synthesis of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4- (difluoromethoxy)phenyl)-2-((4-(methylsulfonamido)phenoxy)carbonyloxy)- ethyl)pyridine 1-oxide (296) To a stirred solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4- (difluoromethoxy)phenyl)-2-((4-nitrophenoxy)carbony loxy)ethyl)pyridine 1 -oxide (prepared in an analogous manner to that described in Example 45, Step 4) (0.140 g, 0.239 mmol) in DCM (5 ml), a solution of N-(4-hydroxyphenyl)- methanesulfonamide (0.0672 g, 0.359 mmol) and DMAP (0.0438 g, 0.359 mmol) in DCM (5 ml) was added drop wise and the reaction was stirred at RT for 3 h. The solvent was evaporated and the resulting crude was purified by chromatography on silica gel column (DCM : MeOH = 10 : 0.4). A second purification by crystallization from absolute ethanol was required to obtain (S)-3,5-dichloro-4-(2-(3- (cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-(methylsulfonamido)- phenoxy)carbonyloxy)ethyl)pyridine 1-oxide as a brown solid (0.050 g, 0.079 mmol, 33% yield, MS/ESI+ 632.74 [MH] +, [ccD] = -36.59, c=0.252, DCM). 1H NMR (300 MHz, DMSO-d6) δ ppm 9.78 (s, 1 H), 8.59 (s, 2 H), 7.17 - 7.25 (m, 3 H), 7.16 (d, 1 H), 7.06 - 7.12 (m, 2 H), 7.03 (dd, 1 H), 7.09 (t, 1 H), 5.90 (dd, 1 H), 3.93 (d, 2 H), 3.57 (dd, 1 H), 3.32 (dd, 1 H), 2.98 (s, 3 H), 1.12 - 1.31 (m, 1 H), 0.52 - 0.70 (m, 2 H), 0.28 - 0.46 (m, 2 H).
  • 50
  • [ 51-78-5 ]
  • [ 124-63-0 ]
  • [ 51767-39-6 ]
YieldReaction ConditionsOperation in experiment
68% In pyridine at 20℃; for 5h; Cooling with ice; 7 6.1.1. N-(4-hydroxyphenyl)naphthalene-2-sulfonamide (3a) General procedure: Under the condition of ice bath, 4-aminophenol hydrochloride 2 (1.46 g, 10 mmol) was dissolved in pyridine (50 mL). After 2-Naphthalenesulfonyl chloride (2.72 g, 12 mmol) was added drop by drop, the mixture was stirred at room temperature for 5 h (detected by TLC). Solvents were evaporated with the residues being taken up in EtOAc (50 mL). Then the organic layer was washed with saturated 1 N HCl (20 mL * 2), distilled water (20 mL * 2), brine (20 mL * 2), dried over anhydrous MgSO4 and evaporated under vacuum. The residues were purified by EtOH/H2O to give desired intermediate 3a.
  • 51
  • [ 51767-39-6 ]
  • [ 919966-54-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: SiO<SUB>2</SUB>-supported NaIO<SUB>4</SUB> / dichloromethane / 2 h / 20 °C 2: N,N-dimethyl-formamide / 4 h / 20 °C
  • 52
  • [ 51767-39-6 ]
  • [ 1329684-17-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: manganese(IV) oxide; acetic acid / 1 h / 25 °C 2: sodium methylate / 1,4-dioxane / 0.5 h / 20 °C
  • 53
  • [ 51767-39-6 ]
  • [ 1397749-85-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: manganese(IV) oxide; acetic acid / 1 h / 25 °C 2: sodium methylate / 1,4-dioxane / 0.5 h / 20 °C 3: hydrogenchloride / water; acetone / 5 h / Reflux 4: thionyl chloride / 3.5 h / 20 - 79 °C 5: pyridine / dichloromethane / 30 - 35 °C
  • 54
  • [ 51767-39-6 ]
  • [ 1278585-70-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: manganese(IV) oxide; acetic acid / 1 h / 25 °C 2: sodium methylate / 1,4-dioxane / 0.5 h / 20 °C 3: hydrogenchloride / water; acetone / 5 h / Reflux 4: thionyl chloride / 3.5 h / 20 - 79 °C 5: pyridine / dichloromethane / 30 - 35 °C 6: aluminum (III) chloride / chlorobenzene / 17 h / 95 °C
  • 55
  • [ 51767-39-6 ]
  • C11H9Cl2N3O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
86.3% With sodium hydride In tetrahydrofuran at 20℃; for 2h; 11 Compound 10 (13.4 g, 71.92 mmol) and 60% NaH (2.88g, 71.92 mmol) were added to THF. After stirring for 2 h at room temperature, compound 5 (12.5 g, 55.31 mmol) wasadded in batches into the solution and stirred for 4 h. Themixture was diluted with saturated NH4Cl (200 mL) andacetic ether (200 mL). The organic layer was washed withsaline (100 mL) and was dried (Na2SO4). The solvent wasremoved by letting the mixture stand under vacuum to producean off-white solid that was then recrystallized fromethyl acetate to afford the product as a white solid (15.8 g,86.3% yield).
  • 56
  • [ 51767-39-6 ]
  • C18H13Cl2F3N4O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C
  • 57
  • [ 51767-39-6 ]
  • C17H14Cl2N4O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C
  • 58
  • [ 51767-39-6 ]
  • C17H13Cl2FN4O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C
  • 59
  • [ 51767-39-6 ]
  • N-(4-(4-(4-chloro-3-(trifluoromethyl)phenylamino)-6-(4-methylpiperazin-1-yl)pyrimidin-2-yloxy)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C 3: 12 h / 110 °C
  • 60
  • [ 51767-39-6 ]
  • N-(4-(4-(4-chloro-3-(trifluoromethyl)phenylamino)-6-morpholinopyrimidin-2-yloxy)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C 3: 12 h / 110 °C
  • 61
  • [ 51767-39-6 ]
  • N-(4-(4-(4-chloro-3-(trifluoromethyl)phenylamino)-6-(piperidin-1-yl)pyrimidin-2-yloxy)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C 3: 12 h / 110 °C
  • 62
  • [ 51767-39-6 ]
  • N-(4-(4-(4-chloro-3-(trifluoromethyl)phenylamino)-6-(diethylamino)pyrimidin-2-yloxy)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C 3: 12 h / 110 °C
  • 63
  • [ 51767-39-6 ]
  • N-(4-(4-(3-chloro-4-fluorophenylamino)-6-(4-methylpiperazin-1-yl)pyrimidin-2-yloxy)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C 3: 12 h / 110 °C
  • 64
  • [ 51767-39-6 ]
  • N-(4-(4-(3-chloro-4-fluorophenylamino)-6-morpholinopyrimidin-2-yloxy)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C 3: 12 h / 110 °C
  • 65
  • [ 51767-39-6 ]
  • N-(4-(4-(3-chloro-4-fluorophenylamino)-6-(pyrrolidin-1-yl)pyrimidin-2-yloxy)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C 3: 12 h / 110 °C
  • 66
  • [ 51767-39-6 ]
  • N-(4-(4-(3-chloro-4-fluorophenylamino)-6-(diethylamino)pyrimidin-2-yloxy)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C 3: 12 h / 110 °C
  • 67
  • [ 51767-39-6 ]
  • N-(4-(4-(4-chlorophenylamino)-6-(4-methylpiperazin-1-yl)pyrimidin-2-yloxy)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C 3: 12 h / 110 °C
  • 68
  • [ 51767-39-6 ]
  • N-(4-(4-(4-chlorophenylamino)-6-morpholinopyrimidin-2-yloxy)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C 3: 12 h / 110 °C
  • 69
  • [ 51767-39-6 ]
  • N-(4-(4-(4-chlorophenylamino)-6-(piperidin-1-yl)pyrimidin-2-yloxy)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydride / tetrahydrofuran / 2 h / 20 °C 2: hydrogenchloride / acetic acid / 3 h / 120 °C 3: 12 h / 110 °C
  • 70
  • [ 73021-84-8 ]
  • C7H6N4O3S [ No CAS ]
  • [ 51767-39-6 ]
YieldReaction ConditionsOperation in experiment
With sodium azide In acetic acid Inert atmosphere; Reaction of quinone imines 1a-1g, 2a-2g, 14a, and 14 b with sodium azide (general procedures). General procedure: a. Sodium azide, 4 mmol, was added in one portion to a solution of 2 mmol of quinone imine 1a-1g, 14a, or 14b in 20 mL of glacial acetic acid. The solution turned red and then became colorless. When the mixture bleached, it was poured onto ice, and the precipitate was filtered off, washed with water, and recrystallized from acetic acid or benzene-hexane (1 : 2) or purified by column chromatography on silica gel. b. A solution of 4 mmol of sodium azide in 10 mL of glacial acetic acid was added dropwise to a solution of 2 mmol of quinone imine 1a-1g or 2a-2g in 10 mL of chloroform or methylene chloride at room temperature or on cooling to -10 °C, and the mixture was purged with argon. The mixture turned red and then bleached. When the reaction was complete, the mixture was evaporated under reduced pressure, and the residue was poured onto ice. The precipitate was filtered off, washed with water, and purified by recrystallization from acetic acid or benzene-hexane (1 : 2) or by column chromatography on silica gel. c. A solution of 2 mmol of quinone imine 1a or 2a was added dropwise under vigorous stirring over a period of 30 min to a solution of 4 mmol of sodium azide in 10 mL of glacial acetic acid maintained at room temperature. The solution immediately turned colorless and was stirred for 1 h and evaporated under reduced pressure. The residue was poured onto ice, the precipitate was extracted with diethyl ether, the extract was dried over magnesium sulfate and evaporated, and the residue was recrystallized from benzene-hexane (1 : 2).
  • 71
  • [ 51767-39-6 ]
  • N-(3-((5-chloro-2-(4-(4-methylsalfonamido)phenoxy)-4-pyrimidinyl)amino)phenyl)-N-methylbenzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium iodide; potassium carbonate / N,N-dimethyl-formamide / 80 °C 2: iron; ammonium chloride / methanol; water / 2 h / 70 °C 3: toluene-4-sulfonic acid / iso-butanol / 12 h / 100 °C
  • 72
  • [ 51767-39-6 ]
  • C13H14N2O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium iodide; potassium carbonate / N,N-dimethyl-formamide / 80 °C 2: iron; ammonium chloride / methanol; water / 2 h / 70 °C
  • 73
  • [ 51767-39-6 ]
  • [ 350-46-9 ]
  • C13H12N2O5S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 80℃;
  • 74
  • [ 51767-39-6 ]
  • N-(4-hydroxy-3-(7-methyl-2-phenylindolizin-3-yl)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: [bis(acetoxy)iodo]benzene / dichloromethane / 1 h / 20 °C 2: acetic acid / acetonitrile / 0.03 h / 25 °C
  • 75
  • [ 51767-39-6 ]
  • N-(4-hydroxy-3-(2-phenylindolizin-3-yl)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: [bis(acetoxy)iodo]benzene / dichloromethane / 1 h / 20 °C 2: acetic acid / acetonitrile / 0.03 h / 25 °C
  • 76
  • [ 51767-39-6 ]
  • N-(4-hydroxy-3-(2-(thiophen-2-yl)indolizin-3-yl)phenyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: [bis(acetoxy)iodo]benzene / dichloromethane / 1 h / 20 °C 2: acetic acid / acetonitrile / 0.03 h / 25 °C
Same Skeleton Products
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