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[ CAS No. 56146-83-9 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 56146-83-9
Chemical Structure| 56146-83-9
Chemical Structure| 56146-83-9
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Product Details of [ 56146-83-9 ]

CAS No. :56146-83-9 MDL No. :MFCD00075558
Formula : C3H5ClO4S Boiling Point : -
Linear Structure Formula :- InChI Key :YBIPZPBGAGTBGK-UHFFFAOYSA-N
M.W : 172.59 Pubchem ID :11435213
Synonyms :

Calculated chemistry of [ 56146-83-9 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.67
Num. rotatable bonds : 3
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 31.58
TPSA : 68.82 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.13 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.98
Log Po/w (XLOGP3) : 0.31
Log Po/w (WLOGP) : 0.81
Log Po/w (MLOGP) : -0.64
Log Po/w (SILICOS-IT) : 0.06
Consensus Log Po/w : 0.31

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -0.91
Solubility : 21.4 mg/ml ; 0.124 mol/l
Class : Very soluble
Log S (Ali) : -1.32
Solubility : 8.3 mg/ml ; 0.0481 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.9
Solubility : 21.8 mg/ml ; 0.126 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.05

Safety of [ 56146-83-9 ]

Signal Word:Danger Class:8
Precautionary Statements:P260-P280-P303+P361+P353-P301+P330+P331-P304+P340+P310-P305+P351+P338+P310 UN#:3265
Hazard Statements:H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 56146-83-9 ]

* 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 [ 56146-83-9 ]

[ 56146-83-9 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 67-56-1 ]
  • [ 4025-77-8 ]
  • [ 56146-83-9 ]
YieldReaction ConditionsOperation in experiment
100% In diethyl ether; at 0℃; for 4h; Example 1 : ./V-(Yl l-(4-(benzyloxy)-2-chloro-phenyl)-6-hydroxy-3,3-dimethyl-l-oxo- 1,2,3,4,5,11 -hexahydrodibenzo|"b,el [ 1 ,4"|diazepin- 10-yl)sulfonyl)acetyl methane sulfonamide (12).; Step 1; O=S=O O=S=OCl 1 Cl 2A solution of 2-chlorosulfonylacetylchloride (1; 1.29 g, 7.27 mmol) and methanol (295 muL, 7.27 mmol) in anhydrous ether (5 mL) was stirred at 00C for 4h. Then, the solvent was evaporated and the residue was triturated in toluene, then evaporated to give 1.26 g (100%) of the target product 2: 1H-NMR (400MHz, CDCl3): delta 3.91 (s, 3H), 4.61 (s, 2H).
97% In diethyl ether; at 0℃; for 3h; Step A; Methyl chlorosulfonylacetate; [Show Image] Chlorosulfonylacetyl chloride (900 mg, 5.08 mmol) was dissolved in diethyl ether (5 ml). Thereafter, methanol (206 mul, 5.08 mmol) was added to the solution at 0C, and the obtained mixture was then stirred at 0C for 3 hours. Thereafter, the temperature of the reaction solution was returned to a room temperature, and the solvent was then distilled away under reduced pressure, so as to obtain methyl chlorosulfonyl acetate (850 mg, 97%) in the form of a colorless oil substance. 1H-NMR (Bruker, 300MHz, CDCl3) delta: 3.91 (s, 3H), 4.61 (s, 2H).
1 g In diethyl ether; at 0 - 20℃; for 2h; To a solution of 2-(chlorosulfonyl)acetyl chloride (1 g, 5.65 mmol) in dry Et2O (5 ml) cooled to 0 C., a solution of methanol (0.286 g, 6.21 mmol) in dry Et2O (1 ml) was added dropwise. After 15 minutes, the mixture was warmed to RT and stirred for 2 hours. The solvent was evaporated and the desired compound was obtained (1 g, 5.36 mmol, 95% yield) and used in the next step without further purification.
1 g In diethyl ether; at 0 - 20℃; for 2h; To a solution of 2-(chlorosulfonyl)acetyl chloride (1 g, 5.65 mmol) in dry Et20 (5 ml) cooled to 0C, a solution of methanol (0.286 g, 6.21 mmol) in dry Et20 (lml) was added dropwise. After 15 min. the mixture was warmed to RT and stirred for 2h. The solvent was evaporated and the desired compound was obtained (1 g, 5.36 mmol, 95% yield) and used in the next step without further purification.
In diethyl ether; at 0℃; for 3h; Step i) [00518] To a solution of chlorosulfonylacetyl chloride (419 mu^, 3.955 mmol, 1 eq.) in Et20 (4 mL), at 0C was added MeOH (160 L, 3.955 mmol, 1 eq.). The reaction mixture is strirred at 0C for 3 h, then concentrated in vacuo to give chlorosulfonyl-acetic acid methyl ester.
In diethyl ether; at 0℃; for 1h; To chlorosulfonyl chloride (3.34 g, 17.9 mmol) in diethyl ether (30 mL) is added at 00C methanol (800 muL, 19.7 mmol). The resulting mixture is stirred at 00C during 1h and the solvent is evaporated to give the title compound.

  • 2
  • [ 67-56-1 ]
  • [ 56146-83-9 ]
  • methoxysulfonyl-acetic acid methyl ester [ No CAS ]
  • 3
  • [ 56146-83-9 ]
  • [ 124-41-4 ]
  • methoxysulfonyl-acetic acid methyl ester [ No CAS ]
  • 4
  • [ 56146-83-9 ]
  • [ 122-39-4 ]
  • diphenylsulfamoyl-acetic acid methyl ester [ No CAS ]
  • 5
  • [ 29508-16-5 ]
  • [ 56146-83-9 ]
  • 6
  • [ 56146-83-9 ]
  • [ 783-08-4 ]
  • [ 126178-19-6 ]
  • 7
  • [ 56146-83-9 ]
  • [ 57120-36-2 ]
  • [ 117765-68-1 ]
  • 8
  • [ 56146-83-9 ]
  • [ 100239-11-0 ]
  • 2-(4-Methoxy-phenyl)-1,1-dioxo-3-(tetrahydro-furan-2-yl)-1λ6-[1,2]thiazetidine-4-carboxylic acid methyl ester [ No CAS ]
  • 9
  • [ 56146-83-9 ]
  • [ 126178-30-1 ]
  • [ 126178-20-9 ]
  • 10
  • [ 56146-83-9 ]
  • [ 138687-67-9 ]
  • (S)-2-((R)-1-Methoxycarbonylmethanesulfonylamino-3-methyl-butylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester [ No CAS ]
  • 11
  • [ 56146-83-9 ]
  • [ 126178-32-3 ]
  • [ 126178-24-3 ]
  • 12
  • [ 56146-83-9 ]
  • [2-Phenyl-eth-(E)-ylidene]-(2-phenylselanyl-ethyl)-amine [ No CAS ]
  • [ 126178-18-5 ]
  • 13
  • [ 56146-83-9 ]
  • (4-Methoxy-phenyl)-[(E)-4-phenyl-but-3-en-(E)-ylidene]-amine [ No CAS ]
  • 2-(4-Methoxy-phenyl)-1,1-dioxo-3-((E)-3-phenyl-allyl)-1λ6-[1,2]thiazetidine-4-carboxylic acid methyl ester [ No CAS ]
  • 14
  • [ 56146-83-9 ]
  • [ 126178-34-5 ]
  • [ 126178-27-6 ]
  • 15
  • [ 56146-83-9 ]
  • [ 126178-33-4 ]
  • [ 126178-26-5 ]
  • 16
  • [ 56146-83-9 ]
  • [ 88304-24-9 ]
  • [ 126178-25-4 ]
  • 17
  • [ 56146-83-9 ]
  • [ 126178-28-7 ]
  • [ 126178-17-4 ]
  • 18
  • [ 56146-83-9 ]
  • [ 126178-31-2 ]
  • 2-(2,4-Dimethoxy-phenyl)-1,1-dioxo-3-(tetrahydro-furan-2-yl)-1λ6-[1,2]thiazetidine-4-carboxylic acid methyl ester [ No CAS ]
  • 19
  • [ 56146-83-9 ]
  • [ 75370-07-9 ]
  • [ 82484-07-9 ]
  • 20
  • [ 56146-83-9 ]
  • [ 105326-65-6 ]
  • [ 119481-37-7 ]
  • 21
  • [ 56146-83-9 ]
  • [ 41505-91-3 ]
  • 22
  • [ 2365-48-2 ]
  • [ 56146-83-9 ]
YieldReaction ConditionsOperation in experiment
100% With chlorine; In dichloromethane; water; at -20 - -6℃; A mixture of mercapto-acetic acid methyl ester (10.0 mL, 111.8 mmol), ice (50 g), and dichloromethane (10 mL) was stirred rapidly in a three neck flask with a mechanical stirrer, thermometer, and gas inlet in an ice/acetone bath chilled to -6 C. Chlorine gas was bubbled through a pipette at a speed to maintain the reaction temperature at -6 C. As the solution became yellow with chlorine saturation, the temperature dropped to -20 C. and gas was bubbled in steadily over 3 hours. The bath was removed, the addition of chlorine stopped, and as soon as solution reached 20 C., the organic phase was separated, washed with brine, dried over sodium sulfate, and filtered. The solvent was evaporated under reduced pressure to yield a clear, colorless oil (19 g, 100%). 1H NMR (400 MHz, CDCl3-d): delta 4.63 (s, 2H), 3.91 (s, 3H).
92% With water; chlorine; In dichloromethane; at 0℃; A solution of mercaptoacetic acid methyl ester (35 mmol) in CH2Cl2 (15 mL) was added dropwise to the ice water (10 mL) and Cl2 was pumped in the solution. The solution was stirred at 0 C until maintaining greenish, followed by pumping N2 to expel Cl2. After standing, the solution was separated. The organic fraction was concentrated under reduced pressure to obtain the title compound. Yellow liquid (92%). 1H NMR (400 MHz, CDCl3) delta = 3.75 (s, 2H, SO2CH2), 3.68 (s, 3H, COOCH3).
83% With chlorine; In dichloromethane; at 0 - 5℃; (i) Methyl 2-(chlorosulphonyl)acetate To a solution of methylthioglycolate (1.3kg, 12.25mol) in dichloromethane (9 litres) was added ice (4.5 litres). Chlorine gas was bubbled gently through the solution, maintaining the temperature below 5C until the solution maintained a slight green colouration. The solution was degassed with nitrogen to remove excess chlorine, the organic phase collected and the solvent removed under reduced pressure to give the subtitle compound (1.758 kg, 83%) which was used without further purification. 1H NMR (CDCl3): 3.91 (3H, s), 4.63 (2H, s).
With oxygen; chlorine; In dichloromethane; at 20 - 30℃; for 7.5h; Step 1: Methyl [methyl(phenyl)amino]sulfonyl}acetate (Compound 5-1) Chlorine gas was passed through a suspension of 230 g of ice, CH2Cl2 (457 ml) and methyl thioglycolate (86 ml, 942 mmol), cooling with an ice/water bath to maintain an internal temperature below 30 C. After approximately six hours, the yellow/green color of the dissolved chlorine persisted for 30 minutes after gas flow was stopped and passing additional chlorine gas was no longer exothermic. The cooling bath was then removed and the biphasic mixture was allowed to stir at ambient temperature for 1 h before being sparged with nitrogen for 20 minutes. The layers were then separated and the organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure to provide the intermediate methyl (chlorosulfonyl)acetate (160 g, 927 mmol) as a yellow oil.
With chlorine; In dichloromethane; water; at 5℃; for 4h; To a solution of methyl 2- mercap to acetate (compound I-15a, 34 g, 320 mmol) in DCM (50 mL) was added H20 (150 mL). Chlorine gas was bubbled gently through the solution, maintaining the temperature below 5 C until the solution maintained a slight green coloration over 4 hours. The solution was extracted with DCM (100 mL) twice. The combined organic layer was dried over anhydrous Na2S04 and concentrated to give compound I-15b (56.6 g, crude) as a yellow oil, which was used in next step directly without further purification

  • 23
  • [ 56146-83-9 ]
  • [ 88-74-4 ]
  • [ 117765-69-2 ]
  • 25
  • [ 56146-83-9 ]
  • [ 62-53-3 ]
  • [ 13229-32-8 ]
YieldReaction ConditionsOperation in experiment
75.3% With pyridine; In dichloromethane; at 20℃; for 12h; A mixture of aniline (0.147 mL, 1.611 mmol) and pyridine (0.156 mL, 1.933 mmol) in dichloromethane (10 mL) was treated at the room temperature with <strong>[56146-83-9]methyl 2-(chlorosulfonyl)acetate</strong> (0.306 g, 1.772 mmol). The reaction mixture was stirred at the same temperature for 12 hr. Then, water was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous 0. iN-hydrochloric acid solution, dried with anhydrous Mg504, filtered, and concentrated in vacuo. The title compound was used without further purification. (methyl 2-(N-phenylsulfamoyl)acetate , 0.300 g, 75.3 %, brown solid).
  • 26
  • [ 56146-83-9 ]
  • [ 62-53-3 ]
  • [ 117765-67-0 ]
  • 27
  • [ 56146-83-9 ]
  • [ 95-54-5 ]
  • [ 117765-73-8 ]
  • 28
  • [ 56146-83-9 ]
  • [ 148016-92-6 ]
  • [ 175846-18-1 ]
  • 29
  • [ 67-56-1 ]
  • [ 56146-83-9 ]
  • [ 85038-34-2 ]
  • 2-Butyl-4-methyl-1,1-dioxo-3-(1-phenyl-ethyl)-1λ6-[1,2]thiazetidine-4-carboxylic acid methyl ester [ No CAS ]
  • 30
  • [ 56146-83-9 ]
  • [ 97578-20-6 ]
  • [Benzyl-(dimethyl-phosphinoylmethyl)-sulfamoyl]-acetic acid methyl ester [ No CAS ]
  • 31
  • [ 56146-83-9 ]
  • [ 174966-20-2 ]
  • [(Dimethyl-phosphinoylmethyl)-methyl-sulfamoyl]-acetic acid methyl ester [ No CAS ]
  • 32
  • [ 56146-83-9 ]
  • [ 174855-56-2 ]
  • [ 210481-94-0 ]
  • 33
  • [ 56146-83-9 ]
  • [ 85503-20-4 ]
  • [ 221249-46-3 ]
YieldReaction ConditionsOperation in experiment
79% With chlorine; In dichloromethane; for 0.5h;Cooling with ice; General procedure: Under ice-cooling, in a solution of methyl 3-mercaptopropionate (6.5 g, 54 mmol) and ice in dichloromethane,Chlorine gas is introduced until the reaction solution turns pale green.Continue to introduce chlorine for 0.5 hours,Nitrogen was purged to remove the chlorine in the reaction system.The reaction was extracted with dichloromethane and the combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give methyl 3-(chlorosulfonyl)propanoate (9.7 g, 96% yield).
65.7% The sodium methoxycarbonylmethylsulfonate salt was added in small portions to a stirred solution of 840 ml (9.14 mols) phosphorus oxychloride. The resulting mixture was then heated at 80-100 C for about 5 hours and allowed to cool overnight. The reaction mixture was filtered, the filtered solid was washed with dichloromethane and the filtrate distilled under reduced pressure to remove the dichloromethane and excess phosphorus oxychloride. The resulting oil residue was distilled through a short Vigreaux column to give 226.8 g (65.7% yield) of methoxycarbonylmethylsulfonyl chloride, as a yellow oil, b.p. 79-80 C. (0.5 mm Hg).
  • 35
  • [ 56146-83-9 ]
  • di-<naphthyl-(2)>-amine [ No CAS ]
  • (di-[2]naphthyl-sulfamoyl)-acetic acid methyl ester [ No CAS ]
  • 36
  • [ 10383-90-1 ]
  • [ 56146-83-9 ]
  • Fmoc-NH-<(S)-CH(CH3)>COO-resin [ No CAS ]
  • [3-13C]-trans-2-((S)-1-carboxyethyl)-4-(methoxycarbonyl)-3-phenyl-1,2-thiazetidine 1,1-dioxide [ No CAS ]
  • 37
  • [ 56146-83-9 ]
  • [ 3218-36-8 ]
  • Fmoc-NH-<(S)-CH(Me)>COO-resin [ No CAS ]
  • (3R,4S)-3-Biphenyl-4-yl-2-((S)-1-carboxy-ethyl)-1,1-dioxo-1λ6-[1,2]thiazetidine-4-carboxylic acid methyl ester [ No CAS ]
  • 38
  • [ 56146-83-9 ]
  • [ 100-52-7 ]
  • Fmoc-NH-<(S)-CH(CH2C6H5)>COO-resin [ No CAS ]
  • (3R,4S)-2-((S)-1-Carboxy-2-phenyl-ethyl)-1,1-dioxo-3-phenyl-1λ6-[1,2]thiazetidine-4-carboxylic acid methyl ester [ No CAS ]
  • 39
  • [ 56146-83-9 ]
  • [ 3218-36-8 ]
  • Fmoc-NH-<CH(CH2OBu-t)>COO-resin [ No CAS ]
  • (3R,4S)-3-Biphenyl-4-yl-2-((S)-2-tert-butoxy-1-carboxy-ethyl)-1,1-dioxo-1λ6-[1,2]thiazetidine-4-carboxylic acid methyl ester [ No CAS ]
  • 40
  • [ 56146-83-9 ]
  • [ 3218-36-8 ]
  • Fmoc-NH-<CH(hexyl)>COO-resin [ No CAS ]
  • (3R,4S)-3-Biphenyl-4-yl-2-(1-carboxy-heptyl)-1,1-dioxo-1λ6-[1,2]thiazetidine-4-carboxylic acid methyl ester [ No CAS ]
  • 41
  • [ 10383-90-1 ]
  • [ 56146-83-9 ]
  • Fmoc-NH-<(S)-CH(CH2CH2CO2Bu-t)>COO-resin [ No CAS ]
  • [3-13C]-trans-2-[(S)-2-(tert-butoxycarbonyl)-1-carboxypropyl]-4-(methoxycarbonyl)-3-phenyl-1,2-thiazetidine 1,1-dioxide [ No CAS ]
  • 42
  • [ 56146-83-9 ]
  • [ 3218-36-8 ]
  • Fmoc-NH-<(S)-CH(CH2C6H11)>COO-resin [ No CAS ]
  • (3R,4S)-3-Biphenyl-4-yl-2-((S)-1-carboxy-2-cyclohexyl-ethyl)-1,1-dioxo-1λ6-[1,2]thiazetidine-4-carboxylic acid methyl ester [ No CAS ]
  • 43
  • [ 56146-83-9 ]
  • [ 79124-76-8 ]
  • Fmoc-NH-<(R)-CH(CH2Pr-i)>COO-resin [ No CAS ]
  • (3R,4S)-2-((R)-1-Carboxy-3-methyl-butyl)-3-[3-(3,4-dichloro-phenoxy)-phenyl]-1,1-dioxo-1λ6-[1,2]thiazetidine-4-carboxylic acid methyl ester [ No CAS ]
  • 44
  • [ 56146-83-9 ]
  • [ 3218-36-8 ]
  • Fmoc-NH-<(S)-CH(CH2CO2Bu-t)>COO-resin [ No CAS ]
  • (S)-2-((3R,4S)-3-Biphenyl-4-yl-4-methoxycarbonyl-1,1-dioxo-1λ6-[1,2]thiazetidin-2-yl)-succinic acid 4-tert-butyl ester [ No CAS ]
  • 45
  • [ 56146-83-9 ]
  • [ 3218-36-8 ]
  • Fmoc-NH-<(S)-CH(CH2C6H4-4-OBu-t)>COO-resin [ No CAS ]
  • (3R,4S)-3-Biphenyl-4-yl-2-[(S)-2-(4-tert-butoxy-phenyl)-1-carboxy-ethyl]-1,1-dioxo-1λ6-[1,2]thiazetidine-4-carboxylic acid methyl ester [ No CAS ]
  • 46
  • [ 56146-83-9 ]
  • [ 79124-76-8 ]
  • Fmoc-NH-<CH(hexyl)>COO-resin [ No CAS ]
  • (3R,4S)-2-(1-Carboxy-heptyl)-3-[3-(3,4-dichloro-phenoxy)-phenyl]-1,1-dioxo-1λ6-[1,2]thiazetidine-4-carboxylic acid methyl ester [ No CAS ]
  • 47
  • [ 56146-83-9 ]
  • [ 79124-76-8 ]
  • Fmoc-NH-<CH(CH2C6H11)>COO-resin [ No CAS ]
  • (3R,4S)-2-((S)-1-Carboxy-2-cyclohexyl-ethyl)-3-[3-(3,4-dichloro-phenoxy)-phenyl]-1,1-dioxo-1λ6-[1,2]thiazetidine-4-carboxylic acid methyl ester [ No CAS ]
  • 48
  • [ 94-45-1 ]
  • [ 56146-83-9 ]
  • (6-ethoxy-benzothiazol-2-ylsulfamoyl)-acetic acid methyl ester [ No CAS ]
  • 49
  • [ 56146-83-9 ]
  • [ 6264-67-1 ]
  • [ 740834-97-3 ]
  • 50
  • [ 56146-83-9 ]
  • [ 1687-53-2 ]
  • [ 740834-96-2 ]
  • 51
  • [ 56146-83-9 ]
  • [ 104-94-9 ]
  • [ 364614-32-4 ]
YieldReaction ConditionsOperation in experiment
80% General procedure: To a solution of amines 12a-f in dichloromethane (20 mL) at 0 C was added triethylamine dropwise and the solution was stirred for 10 min. Methyl 2-(chlorosulfonyl)acetate in dichloromethane (10 mL) was added slowly at the same temperature. The reaction mixture was allowed to warm to room temperature and stirred for overnight after the addition completed. Water was added once the completion of reaction, and the mixture was stirred for 15 min. The organic layer was separated and dried over anhydrous sodium sulphate. Dried residue was evaporated under reduced pressure and was purified by flash column chromatography (silica gel, petroleum ether ramping to ethyl acetate:petroleum ether = 1:1) to give 13a-f.
With pyridine; In acetonitrile; at 20℃;Cooling with ice; 4-methoxyaniline (1.8 g, 14.6 mmol) and pyridine (1.4 g, 17.4 mmol) were dissolved in acetonitrile (35 mL). The solution was cooled in an ice bath and <strong>[56146-83-9]methyl 2-(chlorosulfonyl)acetate</strong> (compound 1, 2.5 g, 14.5 mmol) was slowly added dropwise. The reaction was stirred at room temperature overnight. The solvent was removed from the reaction mixture on a rotary vacuum evaporator, and the residue was dissolved in dichloromethane (100 mL), washed with 1N hydrochloric acid (40 mL) and saturated brine (40 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated to obtain a crude compound 2 (3.46 g, yield: 92%) as a purple oil.
  • 52
  • [ 56146-83-9 ]
  • [ 106-40-1 ]
  • [ 740834-98-4 ]
  • 53
  • [ 110-91-8 ]
  • [ 56146-83-9 ]
  • [ 952423-92-6 ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; at 20℃; for 2h; To <strong>[56146-83-9]chlorosulfonyl-acetic acid methyl ester</strong> (3.39 g, 19.6 mmol) in dichloromethane (50 mL) is added morpholine (8.6 mL, 98 mmol). The resulting mixture is stirred at rt during 2h and the solvent is evaporated to yield the title compound. MS: 223 [M-H]+
  • 54
  • [ 908256-94-0 ]
  • [ 56146-83-9 ]
  • C23H20F3N3O7S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; at 0℃; for 0.5h; The 7-((S)-5-aminomethyl-2-oxooxazolidin-3-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one (20 mg, 0.05 mmol) prepared in step B of Example 2-31 was dissolved in methylene chloride (0.2 ml). Thereafter, the methyl chlorosulfonyl acetate (10.5 mul, 0.05 mmol) obtained in step A was added to the solution under cooling on ice, and the obtained mixture was stirred at 0C for 30 minutes. Thereafter, water was added to the reaction solution, and the mixture was then extracted with methylene chloride. The extract was washed with water and a saline solution, and was then dried over anhydrous magnesium sulfate. Thereafter, the solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel column chromatography (methylene chloride : methanol = 20: 1), so as to obtain a colorless solid (10 mg).
  • 55
  • [ 56146-83-9 ]
  • [ 100-61-8 ]
  • [ 117765-67-0 ]
YieldReaction ConditionsOperation in experiment
A portion of the intermediate methyl (chlorosulfonyl)acetate (100 g, 579 mmol) was added dropwise as a solution in CH2Cl2 (290 ml) to a stirring -15 C. solution of N-methylaniline (124 g, 1159 mmol) dissolved in CH2Cl2 (290 ml). The rate of addition was adjusted to maintain the internal temperature below 5 C. After the addition was complete, the reaction mixture was allowed to warm to room temperature over the course of 2h and 1 M HCl (1000 mL) was added and the aqueous phase was extracted with dichloromethane (2*500 mL). The combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting oil was seed crystallized to afford a brown solid. Recrystallization from hot ethanol (320 mL) provided the title compound as an off-white solid. 1H NMR (600 MHz, DMSO-D6) delta 7.40 (m, 4H); 7.31 (m, 1H); 4.30 (s, 2H); 3.65 (s, 3H); 3.26 (s, 3H). LRMS (APCI) calculated for C25H21N4O3S [M+H]+, 244.1; found 244.0.
4.47 g In dichloromethane; at 0 - 20℃; for 18h; Intermediate 34 /V-methylaniline (4.1 g, 34.28mmol) was dissolved in dichloromethane (50ml_). To this, a solution of <strong>[56146-83-9]methyl 2-(chlorosulfonyl)acetate</strong> (3.3g, 19.12mmol) in dichloromethane (20ml_) was added drop wise at 0C. The mixture was allowed to warm to room temperature and stirred for 18 hours. The mixture was diluted with dichloromethane. The organic layer was washed with water, 1 N hydrochloric acid solution and brine. The organic layer was dried with Na2S04, filtered and concentrated in vacuo to dryness. The residue was purified by chromatography on silica eluting with 0-40% ethyl acetate/cyclohexane. The fractions containing the desired product were combined and the solvents removed by evaporation in vacuo to give Intermediate 34 (4.47g). 1 H NMR (CDCIs) delta: 7.52-7.28 (5H, m), 3.96 (2H, s), 3.79 (3H, s), 3.41 (3H, s)
Example 281 Synthesis of methyl 2-(N-methyl-N-phenylsulfamoyl)acetate. To a solution of N-methylaniline (1.07 g, 10 mmol) in DCM (30 mL) was added <strong>[56146-83-9]methyl 2-(chlorosulfonyl)acetate</strong> (860 mg, 5 mmol) at 0 C. dropwise. The resulting mixture was stirred at RT for 18 h, then quenched with saturated aqueous NH4Cl solution (50 mL) and extracted with EtOAc (100 mL*3). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo to give the crude product which was purified by silica gel column (PE/EtOAc=2/1) to give the <strong>[56146-83-9]methyl 2-(chlorosulfonyl)acetate</strong> as a white solid (850 mg, 70%). ESI-MS [M+H]+: 244.1
  • 56
  • [ 56146-83-9 ]
  • [ 147267-64-9 ]
  • 2-(3-Methoxycarbonylmethylsulfonylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-(3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In tetrahydrofuran; dichloromethane; EXAMPLE 7 2-(3-Methoxycarbonylmethylsulfonylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)- N -(3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide. To a solution of 2-(3-amino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)- N -(3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (0.50 g) in tetrahydrofuran (6 ML), cooled to 0 C, was added, dropwise, methyl chlorosulfonylacetate (0.29 g). Immediately, triethylamine (0.38 g) was added dropwise to the reaction mixture, generating a color change from light orange to green. After 10 min stirring, the reaction mixture was diluted with 25 ML ethyl acetate and acidified with 1 N aqueous hydrochloric acid. The organic phase was washed (water, brine), dried (magnesium sulfate) and evaporated to yield 0.60 g of an orange foam. Chromatography, using acidic silica gel and eluant of methylene chloride:tetrahydrofuran (20:1), followed by overnight vacuum-drying (40 C, 27 Pa), yielded a light-yellow foam (0.35 g); mp 165-168 C; TLC: Rf0.33, dichloromethane:tetrahydrofuran (9:1, trace acetic acid); NMR: 0.90 (2d,6), 2.20 (m,1), 3.70 (s,3), 4.4-4.6 (s and m, 4), 4.65 (t,1), 6.20 (d,1), 7.45 (m,6), 8.75 (d,1), 9.35 (s,1); MS: m/z=532(M+1). The intermediate 2-(3-amino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)- N -(3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide may be prepared as dexcribed in European Patent Application, Publication Number 509769 at Example 49 (and the subparts thereunder); see also Example 22.a.-22.b. and Example 167 of that application.
With triethylamine; In tetrahydrofuran; dichloromethane; EXAMPLE 197 2-(3-Methoxycarbonylmethylsulfonylamino-2-oxo-6-phenyl-1,2-dihydro -1-pyridyl)-N-(3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide. To a solution of 2-(3-amino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-(3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (0.50 g) in tetrahydrofuran (6 mL), cooled to 0 C., was added, dropwise, methyl chlorosulfonylacetate (0.29 g). Immediately, triethylamine (0.38 g) was added dropwise to the reaction mixture, generating a color change from light orange to green. After 10 min stirring, the reaction mixture was diluted with 25 mL ethyl acetate and acidified with 1N aqueous hydrochloric acid. The organic phase was washed (water, brine), dried (magnesium sulfate) and evaporated to yield 0.60 g of an orange foam. Chromatography, using acidic silica gel and eluant of methylene chloride:tetrahydrofuran (20:1), followed by overnight vacuum-drying (40 C., 27 Pa), yielded a light-yellow foam (0.35 g); mp 165-168 C.; TLC: Rf =0.33, dichloromethane:tetrahydrofuran (9:1, trace acetic acid); NMR: 0.90 (2d,6), 2.20 (m,1), 3.70 (s,3), 4.4-4.6 (s and m, 4), 4.65 (t,1), 6.20 (d,1), 7.45 (m,6), 8.75 (d,1), 9.35 (s,1); MS: m/z=532(M+1). Analysis for C22 H24 F3 N3 O7 S: Calculated: C, 49.72; H, 4.55; N, 7.91 Found: C, 50.55; H, 4.79; N, 7.55
  • 57
  • N-((3R,4R)-4-[(5-Chloroindol-2-yl)carbonyl]amino}pyrrolidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide hydrochloride [ No CAS ]
  • [ 56146-83-9 ]
  • methyl 2-[((3R,4R)-3-[(5-chloroindol-2-yl)carbonyl]-amino]-4-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]-pyridin-2-yl)carbonyl]amino}pyrrolidin-1-yl)-sulfonyl]acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 0 - 20℃; [Example 100] methyl 2-[((3R,4R)-3-[(5-chloroindol-2-yl)carbonyl]-amino]-4-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]-pyridin-2-yl)carbonyl]amino}pyrrolidin-1-yl)-sulfonyl]acetate: The compound (230 mg) obtained in Example 95 and triethylamine (0.10 ml) were dissolved in methylene chloride (6.9 ml), and the mixture was cooled with ice.. methoxycarbonylmethanesulfonyl chloride (Synthesis, p. 321, 1975) (105 mg) was added, and the resultant mixture was warmed to room temperature and stirred overnight.. The reaction mixture was diluted with chloroform, washed with water and saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.. The resultant residue was purified by preparative thin-layer chromatography on silica gel (chloroform:methanol = 20:1) and powdered with methanol-water to obtain the title compound (150 mg).1H-NMR (CDCl3) delta: 2.48(3H,s), 2.76-2.86(4H,m), 3.49-3.73(4H,m), 3.87(3H,s), 3.94-3.98(1H,m), 4.08-4.11(1H,m), 4.13(2H,s), 4.69-4.72(1H,m), 4.88-4.91(1H,m), 6.89(1H,s), 7.12-7.15(1H,m), 7.27-7.28(1H,m), 7.50(1H,s), 7.81-7.86(2H,m), 9.92(1H,s). MS (FAB) m/z: 595(M+H+).
  • 58
  • [ 693823-80-2 ]
  • [ 56146-83-9 ]
  • sulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 7H-cyclopenta[b]pyridine; In dichloromethane; at 20℃; for 0.333333h; Example 23 26 Synthesized in two steps: A mixture of amine 13 (0.100 g, 0.23 mmol), CLS02CH2CO2ME (0.039 g, 0.3 mmol), pyrindine (0.49 mL, 0.6 mmol) and DCM (2 mL) was stirred at r. t. for 20 min. The mixture was poured into saturated NAHCO3 and extracted with EtOAc. The organic layer was separated, washed with brine, dried with anhydrous NA2S04, concentrated by rotary evaporation and purified by prep. HPLC to yield the corresponding sulfonamide. The above sulfonamide (0.020 g, 0.038 mmol) was reacted with LAH (0.20 mL, 1 M in THF, 0.2 mmol) in THF (1 mL) at r. t. for 15 min. The reaction mixture was poured into dilute ammonium hydroxide and extracted with EtOAc. The organic layer was separated, washed with brine, dried with anhydrous NA2S04, concentrated by rotary evaporation. Flash chromatography on silica gel with a gradient elution of 15-20% MeOH/DCM mixed with 1-3% NH40H afforded compound 26 as a white solid (0.004 g). MS (ES): 544 [M+H].
  • 59
  • [ 56146-83-9 ]
  • [ 63029-20-9 ]
  • [ 200927-29-3 ]
YieldReaction ConditionsOperation in experiment
With triethylamine;dmap; In dichloromethane; at 20℃; for 26h; Stir a solution containing 8-amino-6-(3-methyl-2-pyridinyl)-1,7-naphthyridine (630 mg, 2.67 mmol), triethylamine (0.45 ML, 3.20 mmol), 4-N,N-dimethylaminopyridine (13 mg) and 90% methyl (chlorosulfonyl acetate (0.61 ML, 3.20 mmol) in dry dichloromethane (50 ML) at room temperature for 26 hours.. Remove volatiles under reduced pressure, triturate the residual oil with diethyl ether and filter the resultant mixture.. Dissolve the filter cake in dichloromethane, wash with water (3x), and evaporate the solvent under reduced pressure.. Flash chromatograph the residue on silica gel, eluding with dichloromethane-methanol-ammonium hydroxide (98:2:0.1), and crystallize the elude from ethanol to obtain the title compound, C17H16N4O4S, mp 147-148.5 C. FABMS: MH+ 373 (100%).
  • 60
  • [ 200928-42-3 ]
  • [ 56146-83-9 ]
  • methyl [[2-[6-(3-methyl-2-pyridinyl)-1,7-naphthyridin-8-yl]hydrazino]sulfonyl]acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; triethylamine; In dichloromethane; water; Example 42 Methyl [[2-[6-(3-methyl-2-pyridinyl)-1,7-naphthyridin-8-yl]hydrazino]sulfonyl]acetate STR58 To a stirred solution of 8-hydrazino-6-(3-methyl-2-pyridinyl)-1,7-naphthyridine (1.09 g, 4.34 mmol), triethylamine (0.67 mL, 4.81 mmol) and 4-dimethylaminopyridine (18 mg) in dichloromethane (75 mL), add a solution of methyl 2-chlorosulfonyl acetate (0.83 g, 4.81 mmol) in dichloromethane (25 mL), and stir the resultant mixture at room temperature for 23 hours. Concentrate the reaction mixture under vacuum, triturate the residue with water (50 mL), filter and flash chromatograph the solids on silica gel, eluding with dichloromethane-methanol-ammonium hydroxide (95:5:0.1) to obtain the title compound, C17 H17 N5 O4 S, mp 139.5-140.5 C. (dec). FABMS: MH+ 388 (100%).
With dmap; triethylamine; In dichloromethane; at 20℃; for 23h; To a stirred solution of 8-hydrazino-6-(3-methyl-2-pyridinyl)-1,7-naphthyridine (1.09 g, 4.34 mmol), triethylamine (0.67 ML, 4.81 mmol) and 4-dimethylaminopyridine (18 mg) in dichloromethane (75 ML), add a solution of methyl 2-chlorosulfonyl acetate (0.83 g, 4.81 mmol) in dichloromethane (25 ML), and stir the resultant mixture at room temperature for 23 hours. Concentrate the reaction mixture under vacuum, triturate the residue with water (50 ML), filter and flash chromatograph the solids on silica gel, eluding with dichloromethane-methanol-ammonium hydroxide (95:5:0.1) to obtain the title compound, C17H17N5O4S, mp 139.5-140.5 C (dec). FABMS: MH+ 388 (100%).
  • 61
  • 3-(7-amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1,1-dipropylnaphthalen-2(1H)-one Trifluoroacetate [ No CAS ]
  • [ 56146-83-9 ]
  • methyl ([3-(1-hydroxy-3-oxo-4,4-dipropyl-3,4-dihydronaphthalen-2-yl)-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]amino}sulfonyl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
34% EXAMPLE 83 Methyl([3-(1-hydroxy-3-oxo-4,4-dipropyl-3,4-dihydronaphthalen-2-yl)-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]amino}sulfonyl)acetate Example 71 (50 mg, 0.11 mmol) was dissolved in 2.2 mL of acetone, treated with pyridine (71 muL, 0.88 mmol) and chlorosulfonyl acetic acid methyl ester (63 muL, 0.55 mmol), stirred for 16 h, partitioned between ethyl acetate and 1% aqueous citric acid. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography with a gradient of methanol in dichloromethane (0-2%) to afford the desired product (22 mg, 34% yield). 1H NMR (300 MHz, DMSO-d6) delta ppm 0.57 (m, 2H) 0.68 (m, 6H) 0.90 (m, 2H) 2.00 (m, 2H) 2.18 (m, 2H) 3.64 (s, 3H) 4.37 (s, 2H) 7.57 (m, 3H) 7.75 (m, 3H) 8.16 (d, J=7.72 Hz, 1H) 10.68 (s, 1H) 13.76 (s, 1H); MS (ESI+) m/z 576 (M+H)+, (ESI+) m/z 593 (M+NH4)+ (ESI+) m/z 1173 (2M+Na)+ (ESI-) m/z 574 (M-H)-.
34% With pyridine; In acetone; for 16h; Example 71 (50 mg, 0.11 mmol) was dissolved in 2.2 mL of acetone, treated with pyridine (71 L, 0. 88 mmol) and CHLOROSULFONYL acetic acid methyl ester (63 ZL, 0.55 mmol), stirred for 16h, partitioned between ethyl acetate and 1% aqueous citric acid. The organic phase was washed with brine, dried over NA2S0¢, FILTERED and concentrated in vacuo. The crude material was purified by silica gel chromatography with a gradient of methanol in dichloromethane (0-2%) to afford the desired product (22 mg, 34% yield).'H NMR (300 MHz, DMSO-D6) 8 PPM 0. 57 (M, 2 H) 0.68 (M, 6 H) 0. 90 (M, 2 H) 2.00 (M, 2 H) 2.18 (M, 2 H) 3.64 (s, 3 H) 4.37 (s, 2 H) 7.57 (M, 3 H) 7.75 (M, 3 H) 8.16 (d, J=7.72 Hz, 1 H) 10. 68 (s, 1 H) 13.76 (s, 1 H); MS (ESI+) m/z 576 (M+H) +, (ESI+) M/Z 593 (M+NH4) + (ESI+) M/Z 1173 (2M+NA) + (ESI-) m/z 574 (M-H)-.
  • 62
  • [ 847441-49-0 ]
  • [ 56146-83-9 ]
  • [ 847441-76-3 ]
YieldReaction ConditionsOperation in experiment
68% EXAMPLE 114 Methyl [({3-[1-hydroxy-4-methyl-4-(3-methylbutyl)-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}amino)sulfonyl]acetate Example 87 (100 mg, 0.21 mmol) was dissolved in 5 mL of acetone and treated with <strong>[56146-83-9]chlorosulfonyl-acetic acid methyl ester</strong> (150 uL, 0.87 mmol) and pyridine (150 uL, 1.90 mmol). The mixture was stirred at room temp over night, diluted with ethyl acetate, washed with water and 10% citric acid and water, and concentrated in vacuo. The crude material was chromatographed on silica gel with a gradient methanol in dichloromethane (0-5%) to afford the title compound (83 mg, 68%). 1H NMR (300 MHz, DMSO-d6) delta ppm 0.41 (m, J=7.72 Hz, 1H) 0.69 (d, J=6.62 Hz, 3H) 0.72 (d, J=6.62 Hz, 3H) 0.82 (m, 1H) 1.31 (m, J=13.05, 6.80 Hz, 1H) 1.57 (s, 3H) 2.05 (m, 1H) 2.22 (m, 1H) 3.64 (s, 3H) 4.38 (s, 2H) 7.57 (m, 3H) 7.74 (m, 3H) 8.16 (d, J=8.09 Hz, 1H) 10.68 (s, 1H) 13.82 (s, 1H); MS (APCI) m/z 574 (M-H)-.
  • 63
  • [ 56146-83-9 ]
  • [ 74-89-5 ]
  • [ 291306-38-2 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; at 5℃; for 1h; (ii) Methyl 2-[(methylamino)sulphonyl]acetate To a solution of the product of step (i) (75g) in tetrahydrofuran (150ml) at 5C was added a solution of methylamine in tetrahydrofuran (2M solution, 435ml) over one hour. The yellow slurry was allowed to warm to room temperature and after one hour water (750ml) added. Ethyl acetate (750ml) was added and the aqueous phase extracted with ethyl acetate (500ml). The organics were combined and the solvent removed under reduced pressure to give the subtitle compound (40.2g) which was used without further purification. 1H NMR (CDCl3): 2.90 (3H, m), 3.75 (3H, s), 4.05 (2H, s), 4.77 (1H, br)
  • 64
  • [ 56146-83-9 ]
  • [ 121561-15-7 ]
  • [ 856695-83-5 ]
YieldReaction ConditionsOperation in experiment
With pyridine;dmap; In dichloromethane; at 20℃; for 48h; Methyl 4- ( ( [2- (methyloxy)-2-oxoethyl] sulfonyl) amino)-lH-indole-6-carboxylate (D14) A solution of methyl 4-amino-1 H-indole-6-carboxylate (D3) (9 g, 47 mmol) in dichloromethane (180 mi) was treated with pyridine (5.8 ml) and DMAP (0.577 g) and then methyl (chlorosulfonyl) acetate [56146-83-9] (8.63 g, 50 mmol) was added dropwise. The resulting black mixture was stirred at room temperature overnight. An additional quantity of methyl (chlorosulfonyl) acetate (1.2 g) was added and the mixture stirred for a further 48 hours at room temperature. The mixture was diluted with ethyl acetate and washed sequentially with saturated aqueous sodium hydrogen carbonate and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting solid was triturated with ether to give the crude title compound (D14) as a brown solid (9.37 g). [M- H]- = 325. 2, RT=2. 14min
  • 65
  • [ 31252-42-3 ]
  • [ 56146-83-9 ]
  • [ 227304-79-2 ]
YieldReaction ConditionsOperation in experiment
In methanol; PREPARATION 13 Methyl 2-(4-benzylpiperidin-1-ylsulphonyl)acetate Obtained as an amorphous solid (24%) from 4-benzylpiperidine and methyl chlorosulphonylacetate, using the procedure of Preparation 8, but with an elution gradient of dichloromethane:methanol (100:0 to 95:5) for the chromatographic purification step. delta(CDCl3): 1.30 (m,2H), 1.62 (m,1H), 1.70 (m,2H), 2.54 (d,2H), 2.78 (t,2H), 3.73 (s,3H), 3.76 (m,2H), 3.88 (s,2H), 7.08 (d,2H), 7.17 (t,1H), 7.24 (m,2H). LRMS (APCI): 312 (M+H)+.
  • 66
  • [ 239074-42-1 ]
  • [ 56146-83-9 ]
  • [ 239073-58-6 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In dichloromethane; 1) To a solution of 1-[4-(1-imidazolyl)benzyl]piperazin-2-one (586 mg) and diisopropylethylamine (388 mg) in dichloromethane (10 ml) was added dropwise, under ice-cooling, a solution of methyl chlorosulfonylacetate (380 mg) in dichloromethane (10 ml), and the mixture was stirred at room temperature overnight. The reaction solution was washed with 0.5N hydrochloric acid and saturated brine, dried and concentrated, and the residue was purified with silica gel column chromatography (eluent:methanol/dichloromethane=1/10) to give colorless oil of 1-[4-(1-imidazolyl)benzyl]-4-methoxycarbonylmethylsulfonyl-2-oxopiperazine (0.170 g). 1H-NMR (CDCl3) delta: 3.38-3.43 (2H, m), 3.61-3.66 (2H, m), 3.80 (2H, s), 4.08 (2H, s), 4.14 (2H, s), 7.20 (1H, s), 7.30 (1H, s), 7.40 (4H, s), 7.87 (1H, s). IR (KBr): 3119, 2928, 1746, 1651, 1615, 1522, 1489, 1435 cm-1.
  • 67
  • [ 10338-69-9 ]
  • [ 56146-83-9 ]
  • [ 227304-77-0 ]
YieldReaction ConditionsOperation in experiment
PREPARATION 11 Methyl 2-(4-phenyl-1,2,3,6-tetrahydropyridin-1-ylsulphonyl)acetate Obtained as a colourless solid (20%), m.p. 93-94 C., from 4-phenyl-1,2,3,6-tetrahydropyridine and methyl chlorosulphonylacetate, using the procedure of Preparation 8. Found: C, 56.86; H, 5.79; N, 4.76, C14H17NO4S requires C, 56.93; H, 5.80; N, 4.74%. delta(CDCl3): 2.62 (m,2H), 3.60 (t,2H), 3.78 (s,3H), 3.99 (s,2H), 4.05 (m,2H), 6.00 (brs,1H), 7.22-7.35 (m,5H).
  • 68
  • [ 771-99-3 ]
  • [ 56146-83-9 ]
  • [ 227304-78-1 ]
YieldReaction ConditionsOperation in experiment
PREPARATION 12 Methyl 2-(4-phenylpiperidin-1-ylsulphonyl)acetate Obtained as a colourless solid (35%), m.p. 98-100 C., from 4-phenylpiperidine and methyl chlorosulphonylacetate, using the procedure of Preparation 8. Found: C, 56.43; H, 6.41; N, 4.64. C14H19NO4S requires C, 56.55; H, 6.44; N, 4.71%. delta(CDCl3): 1.80 (m,2H), 1.90 (m,2H), 2.60 (m,1H), 2.97 (m,2H), 3.80 (s,3H), 3.92 (s,2H), 3.93 (m,2H), 7.15-7.33 (m,5H).
  • 69
  • [ 202650-20-2 ]
  • [ 56146-83-9 ]
  • 5-[2-(2-Hydroxy-3-phenoxy-propylamino)-propyl]-1-(4-methoxycarbonyl-methanesulfonylamino-benzyl)-1H-indole-2-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; 2g. 5-[2-(2-Hydroxy-3-phenoxy-propylamino)-propyl]-1-(4-methoxycarbonyl-methanesulfonylamino-benzyl)-1H-indole-2-carboxylic Acid To an about -78 C. solution of 1-(4-amino-benzyl)-5-{2-[tert-butoxycarbonyl-(2-hydroxy-3-phenoxy-propyl)-amino]-propyl}-1H-indole-2-carboxylic acid (110 mg, 0.19 mmol) in methylene chloride (12 ml) was added triethylamine (59 ml, 0.43 mmol) and <strong>[56146-83-9]chlorosulfonyl-acetic acid methyl ester</strong> (39.9 mg, 0.232 mmol). After stirring for about 15 mins and then allowing to warm to ambient temperature over about 1 hr the solution was partitioned between water and methylene chloride and then the organic layer was washed once with brine, dried over sodium sulfate, filtered, and then concentrated in vacuo to afford a foam (121 mg). This foam was redissolved in methylene chloride (7.5 ml) and cooled to about 0 C. before adding 2.5 ml of TFA (to generate a 25% TFA solution).
With triethylamine; In dichloromethane; 2g. 5-[2-(2-Hydroxy-3-phenoxy-propylamino)-propyl]-1-(4-methoxy-carbonyl-methanesulfonylamino-benzyl)-1H-indole-2-carboxylic acid To an about -78C solution of 1-(4-amino-benzyl)-5-{2-[tert-butoxy-carbonyl-(2-hydroxy-3-phenoxy-propyl)-amino]-propyl}-1H-indole-2-carboxylic acid (110 mg, 0.19 mmol) in methylene chloride (12 ml) was added triethylamine (59 ml, 0.43 mmol) and <strong>[56146-83-9]chlorosulfonyl-acetic acid methyl ester</strong> (39.9 mg, 0.232 mmol). After stirring for about 15 mins and then allowing to warm to ambient temperature over about 1 hr the solution was partitioned between water and methylene chloride and then the organic layer was washed once with brine, dried over sodium sulfate, filtered, and then concentrated in vacuoto afford a foam (121 mg). This foam was redissolved in methylene chloride (7.5 ml) and cooled to about 0C before adding 2.5 ml of TFA (to generate a 25% TFA solution).
  • 70
  • [ 56146-83-9 ]
  • [ 2357-47-3 ]
  • 2-[N-(4-fluoro-3-trifluoromethylphenyl)sulfamoyl]-acetic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
84.35% In pyridine; 1,1-dichloroethane; (a) 2-[N-(4-fluoro-3-trifluoromethylphenyl)sulfamoyl]-acetic acid methyl ester Analogously to the instructions for example 7, 5 g (27.64 mmol) of 4-fluoro-3-(trifluoromethyl)-aniline in 25 ml of dry pyridine is reacted with 4.82 g (27.4 mmol) of chlorosulfonyl acetic acid methyl ester in 100 ml of dry dichloroethane. After crystallization from ether/hexane, 7.35 g=84.35% of the theoretical yield is obtained. Melting point 111-112 C.
With pyridine; In dichloromethane; 2-[N-(4-Fluoro-3-trifluoromethylphenyl)sulfamoyl]acetic Acid Methyl Ester 13.02 g (72.70 mmol) of 4-fluoro-3-trifluoromethylaniline and 6.79 ml (84.12 mmol) of pyridine are dissolved in 350 ml of dichloromethane. The mixture is cooled to 0 C. and then, under agitation and exclusion of moisture, 13.2 g (72.70 mmol) of 2-chlorosulfonylacetic acid methyl ester (95.3%), dissolved in 50 ml of dichloromethane, is added dropwise thereto. After agitation overnight, the mixture is washed with 2N hydrochloric acid and water. The dichloromethane solution is dried over sodium sulfate, concentrated to dryness under vacuum, and the residue is crystallized from diethyl ether/hexane. The title compound melts at 111-113 C. Yield: 19.86 g (86.7% of theory)
  • 71
  • 2-(4,6-dimethoxypyrimidin-2-yloxy)-6-fluoroaniline [ No CAS ]
  • [ 56146-83-9 ]
  • methyl [2-(4,6-dimethoxypyrimidin-2-yloxy)-6-fluorophenylsulfamoyl]acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; In dichloromethane; (a) Methyl [2-(4,6-dimethoxypyrimidin-2-yloxy)-6-fluorophenylsulfamoyl]acetate Methyl (chlorosulfonyl)acetate (13.0 g) in dichloromethane (20 ml) was added dropwise with stirring and cooling to 2-(4,6-dimethoxypyrimidin-2-yloxy)-6-fluoroaniline (20 g) and pyridine (6.3 g) in dichloromethane (120 ml). After stirring for 2 hours, the mixture was allowed to stand at room temperature overnight. Washing with dilute hydrochloric acid and water, drying over magnesium sulfate, and running down, gave an oil which was triturated with ether. The resulting off-white solid was separated by filtration to give 20.4 g of the desired product, mp 111-114 C.
  • 72
  • [ 4377-41-7 ]
  • [ 56146-83-9 ]
  • [ 105326-65-6 ]
  • [[[3-(2-Quinolinyl)phenyl]amino]sulfonyl]acetic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; EXAMPLE 7 [[[3-(2-Quinolinyl)phenyl]amino]sulfonyl]acetic acid methyl ester A solution of 11 g (0.044 mol) of 3-[(2-quinolinyl)methoxy]benzenamine, prepared from 2-(chloromethyl)quinoline using the procedure of Example 5, steps A and B, and 4.5 g (0.044 mol) of triethylamine in 250 ml of methylene chloride is cooled to 0 C. A solution of 7.6 g (0.044 mol) of chlorosulfonylacetic acid methyl ester in 100 ml of methylene chloride is added from a dropping funnel and the mixture is allowed to warm to room temperature. The methylene chloride solution is twice washed with water, dried over anhydrous magnesium sulfate and concentrated to obtain 17 g of an oil, which is subjected to high pressure liquid chromatography (ethyl acetate/hexane as eluent). Fractions 3-9 are combined and concentrated to obtain a residue, which upon trituration with ether gives 11.5 g of crystals. Recrystallization from ethanol gives 6.5 g (37%) of crystals, m.p. 120-122 C. Analysis for: C19 H18 N2 O5 S: Calculated: C, 59.05; H, 4.69; N, 7.25; S, 8.30. Found: C, 59.03; H, 4.69; N, 7.16; S, 8.25.
  • 73
  • [ 56146-83-9 ]
  • [ 363-81-5 ]
  • [ 130046-15-0 ]
YieldReaction ConditionsOperation in experiment
55.79% With pyridine; hydrogenchloride; In 1,1-dichloroethane; Example 4 2-[N-(2,4,6 Trifluorophenyl)sulfamoyl]-acetic acid methyl ester 0.76 g (5 mmol) of 2,4,6-trifluoroaniline is dissolved in 40 ml of dichloroethane with exclusion of moisture, 0.4 ml (5 mmol) of pyridine is added, 0.86 g (5 mmol) of chlorosulfonyl acetic acid methyl ester, dissolved in 10 ml of dichloroethane, is instilled at 0 C. and then it is stirred for 1 hour at 0 C. and 12 hours at room temperature. The reaction solution is then shaken out twice with 10 ml of 2N hydrochloric acid each, the phases are separated, the organic phase is dried on magnesium sulfate, filtered and evaporated to dryness. The residue is crystallized from diethyl ether/pentane 1:1. 790 mg (2.79 mmol)=55.79% of the theoretical yield is obtained as a crystallizate. Melting point 99-100 C.
  • 74
  • [ 56146-83-9 ]
  • [ 393-39-5 ]
  • [ 130046-18-3 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In pyridine; dichloromethane; Example 7 2-[N-(4-Fluoro-2-trifluoromethylphenyl)sulfamoyl]-acetic acid methyl ester 5 g (27.64 mmol) of 4-fluoro-2-(trifluoromethyl)-aniline is dissolved in 25 ml of dry pyridine and the solution is cooled to 0 C. A solution of 4.82 g (27.4 mmol) of chlorosulfonyl acetic acid methyl ester in 20 ml of dichloromethane is instilled in the cooled solution in the course of about 10 minutes with the temperature being maintained. Then it is stirred for 6 hours at room temperature. The reaction solution is then diluted with 100 ml of dichloromethane, the pyridine is shaken out with 2N hydrochloric acid, the organic phase is dried on magnesium sulfate, filtered and evaporated to dryness. The residue is crystallized from diethyl ether/hexane yield is obtained as a crystallizate. Melting point 84-86 C.
  • 75
  • [ 56146-83-9 ]
  • [ 103-67-3 ]
  • methyl (N-benzyl-N-methylsulfamoyl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% In hexane; dichloromethane; water; (a) Methyl (N-benzyl-N-methylsulfamoyl)acetate To a stirred solution of N-methyl benzylamine (7 ml, 54.2 mmol) in dichloromethane (10 ml) at 0-5 C. under an atmosphere of nitrogen was added dropwise a solution of methyl chlorosulfonylacetate (prepared by the method of M. J. Szymonifka and J. V. Heck, Tetrahedron Lett., 1989, 30, 22, 2869) (4.26 g, 24.7 mmol) in dichloromethane (5 ml), maintaining the temperature below 5 C. The yellow solution was then warmed to ambient temperature over a 2 hr period before water (30 ml) was added. The organic phase was partitioned and evaporated in vacuo to give a yellow oil. This was purified by flash column chromatography (diethyl ether:hexane 1:1 as eluant) to give the subtitle compound (3.9 g, 61%) as a colourless oil. 1H NMR (300 MHz, CDCl3) delta=2.83 (3H, s), 3.83 (3H, s), 4.02 (2H, s), 4.38 (2H, s), 7.27-7.42 (5H, m). Found: C, 51.31; H, 5.92; N, 5.42. C11H15NO4S requires C, 51.35; H, 5.88; N, 5.44%.
  • 76
  • [ 56146-83-9 ]
  • [ 14683-47-7 ]
  • methyl (N-diphenylmethyl-N-methylsulfamoyl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% (a) Methyl (N-diphenylmethyl-N-methylsulfamoyl)acetate The subtitle compound (3.05 g, 37%) was prepared as a clear brown oil from N-methyl benzhydrylamine (prepared according to the method of Z. Horii, T Sakai and Inoi, Pharm Bull., 1955, 3, 159) (10.7 g, 50.7 mmol) and methyl chlorosulfonylacetate (4.27 g, 24.7 mmol), using the method of Example 1(a). 1H NMR (300 MHz, CDCl3) delta=2.84 (3H, s), 3.72 (3H, s), 3.82 (2H, s), 6.43 (1H, s) 7.10-7.47(10H, m). Found: C, 61.29; H 5.74; N, 4.21. C17H19O4NS requires C, 61.24; H 5.74; N, 4.20%.
  • 77
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  • [ 233283-91-5 ]
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  • [ 143867-44-1 ]
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  • [ 227304-76-9 ]
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  • [ 227304-96-3 ]
  • [ 56146-83-9 ]
  • [ 227304-97-4 ]
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  • [ 202716-30-1 ]
  • [ 56146-83-9 ]
  • [ 227305-11-5 ]
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  • [ 1000989-19-4 ]
  • [ 56146-83-9 ]
  • [ 1000989-26-3 ]
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  • [ 227304-75-8 ]
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  • [ 1000989-27-4 ]
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  • [ 227306-22-1 ]
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