There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
Inaccessible (Haz class 6.1), International | USD 150+ |
Accessible (Haz class 3, 4, 5 or 8), Domestic | USD 100+ |
Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 42899-76-3 | MDL No. : | MFCD04035552 |
Formula : | C5H5Cl2NO2S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | VIVPWOMJFLICOZ-UHFFFAOYSA-N |
M.W : | 214.07 | Pubchem ID : | 12571517 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 44.29 |
TPSA : | 55.41 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.35 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 1.77 |
Log Po/w (WLOGP) : | 2.89 |
Log Po/w (MLOGP) : | 0.24 |
Log Po/w (SILICOS-IT) : | 0.91 |
Consensus Log Po/w : | 1.16 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.62 |
Solubility : | 0.514 mg/ml ; 0.0024 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.55 |
Solubility : | 0.601 mg/ml ; 0.00281 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.56 |
Solubility : | 0.584 mg/ml ; 0.00273 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.85 |
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P260-P280-P303+P361+P353-P301+P330+P331-P304+P340+P310-P305+P351+P338+P310 | UN#: | 3261 |
Hazard Statements: | H314 | Packing Group: | Ⅲ |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.9% | at 85℃; | 21.4 g (0.100 mol) of pyridine-3-sulfonyl chloride hydrochloride and 42.8 g of monochlorobenzene were placed in a 200 mL four-necked flask, and the slurry Liquid). The internal pressure was adjusted to 23 kPa using a vacuum pump and heated to 85 ± 5 ° C. for 5 hours (dehydrochlorination). After 5 hours, the contents of the flavor became almost transparent liquid. Thereafter, monochlorobenzene was distilled off under reduced pressure (100 ° C., 27 kPa). Subsequently, distillation under reduced pressure (110 ° C., 1 kPa) gave 16.5 g (0.0929 mol, yield 92.9percent) of pyridine-3-sulfonyl chloride. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With ammonia In methanol; dichloromethane at 20℃; for 0.833333 h; | Example 79; N-(6-(2-(pyridine-5-sulfonamido)pyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide; Step 1. Pyridine-3 -sulfonamide; Pyridine-3-sulfonyl chloride HCl (647.2 mg, 3.023 mmol) was suspended in DCM (9.0 mL) and NH3 (5 mL, 7N in MeOH, 35 mmol) was added. The reaction was stirred at RT under nitrogen for 50 minutes and then filtered, and the solid was washed with DCM. The filtrate was concentrated and dried under high vacuum to provide pyridine-3 -sulfonamide (477 mg , 91percent yield). MS (ESI pos. ion) m/z: 159(MH+). Calculated exact mass for C5H6N2O2S: 158. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Stage #1: at 120℃; for 15 h; Stage #2: With hydrogenchloride In chloroform |
Intermediate 23; Pyridine-3-sulfonyl chloride hydrochloride; Pyridine-3 -sulfonic acid (3.00 g, 18.8 mmol) and PCl5 (4.79 g, 23.0 mmol) were mixed in POCI3 (6 mL). The reaction was stirred and refiuxed at 120 °C over night (15 h). Cooled to rt., diluted with CHCl3 (20 mL) and saturated with HCl (g). This gave a white precipitation, which was filtered off, washed with CHCl3 and dried under reduced pressure to give the title compound (3.36 g, 83percent) as a white powder. |
81% | Stage #1: at 120℃; for 8 h; Stage #2: With hydrogenchloride In chloroform at 20℃; |
Reference Example 29 pyridin-3-ylsulfonyl chloride hydrochloride; A mixture of 3-pyridinesulfonic acid (50.0 g), phosphorus pentachloride (80.0 g) and phosphorus oxychloride (100 mL) was stirred at 120° C. for 8 hr. Under a nitrogen atmosphere, the mixture was cooled to room temperature, and chloroform (dehydrated, 330 mL) was added. Hydrogen chloride was blown in, and the precipitated crystals were collected by filtration and washed with chloroform (dehydrated) to give the title compound as a white solid (yield 54.7 g, 81percent). 1H-NMR (DMSO-d6) δ: 8.03-8.07 (1H, m), 8.68 (1H, d, J=8.1 Hz), 8.87 (1H, d, J=5.7 Hz), 9.01 (1H, s). |
81% | With phosphorus pentachloride; trichlorophosphate In chloroform at 120℃; for 8 h; | Reference Example 132 Pyridin-3-ylsulfonyl chloride hydrochloride A mixture of 3-pyridinesulfonic acid (50.0 g), phosphorus pentachloride (80.0 g) and phosphorus oxychloride (100 mL) was stirred at 120°C for 8 hr. Under a nitrogen atmosphere, the mixture was cooled to room temperature, and chloroform (dehydrated, 330 mL) was added. Hydrogen chloride was blown in, and the precipitated crystals were collected by filtration and washed with chloroform (dehydrated) to give the title compound as a white solid (yield 54.7 g, 81percent). 1H-NMR (DMSO-d6)δ: 8.03-8.07 (1H, m), 8.68 (1H, d, J=8.1 Hz), 8.87 (1H, d, J=5.7 Hz), 9.01 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 10 - 35℃; for 0.5 h; Stage #2: With 15-crown-5 In tetrahydrofuran; mineral oil for 0.5 h; Stage #3: for 3 h; |
Reference Example 245 5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde To a solution (96 mL) of 5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde (475 mg) in tetrahydrofuran was added sodium hydride (60percent in oil, 503 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (2.77 g) was added dropwise and the mixture was stirred for 30 min, pyridine-3-sulfonyl chloride hydrochloride (1.35 g) was added, and the mixture was further stirred for 3 hr. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:3→2:3), and crystallized from diisopropyl ether-ethyl acetate (4:1) to give the title compound as colorless crystals (yield 680 mg, 82percent). 1H-NMR (CDCl3)δ: 6.68 (1H, d, J=1.8 Hz), 6.99-7.05 (1H, m), 7.16-7.19 (2H, m), 7.35-7.39 (1H, m), 7.45-7.51 (1H, m), 7.69-7.73 (1H, m), 8.14 (1H, d, J=1.8 Hz), 8.58-8.59 (1H, m), 8.81-8.83 (1H, m), 9.91 (1H, s). |
78% | Stage #1: With dmap; N-ethyl-N,N-diisopropylamine In acetonitrile at 45℃; for 5 h; Stage #2: With hydrogenchloride In water; acetonitrile at 10 - 20℃; for 1.5 h; |
A total of 0.5g, 4-dimethylaminopyridine 90mg, 5ml acetonitrile, take N, N-diisopropylethylamine1.5g with a small amount of acetonitrile dissolved in the above reaction bottle, take pyridine-3-sulfonyl chloride hydrochloride 1.1g, with 5mlAcetonitrile dissolved into the reaction flask, heated to 45 ° C stirring reaction 5h after cooling to room temperature, adding 5ml of water,The pH was adjusted to 5 with 0.5 N hydrochloric acid solution, and 20 ml of water was slowly added dropwise (at this time, a large amount of white solid precipitated)Stirring at room temperature for 0.5h, cooling to below 10 , stirring 1h, filtration, filter cake with a small amount of acetonitrile and water mixtureWashing, 50 ° C drying was V total of 0.69g, yield 78percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: With sodium hydride In tetrahydrofuran at 20℃; for 0.5 h; Stage #2: With 15-crown-5 In tetrahydrofuran at 20℃; for 0.5 h; Stage #3: for 3 h; |
Reference Example 63 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; To a solution (96 mL) of 5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde (475 mg) in tetrahydrofuran was added sodium hydride (60percent in oil, 503 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (2.77 g) was added dropwise and the mixture was stirred for 30 min. Pyridine-3-sulfonyl chloride hydrochloride (1.35 g) was added, and the mixture was further stirred for 3 hr. The reaction mixture was diluted with saturated brine, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:3-->2:3) and crystallized from diisopropyl ether-ethyl acetate (4:1) to give the title compound as colorless crystals (yield 680 mg, 82percent). 1H-NMR (CDCl3) δ: 6.68 (1H, d, J=1.8 Hz), 6.99-7.05 (1H, m), 7.16-7.19 (2H, m), 7.35-7.39 (1H, m), 7.45-7.51 (1H, m), 7.69-7.73 (1H, m), 8.14 (1H, d, J=1.8 Hz), 8.58-8.59 (1H, m), 8.81-8.83 (1H, m), 9.91 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Intermediate 23; Pyridine-3-sulfonyl chloride hydrochloride; Pyridine-3 -sulfonic acid (3.00 g, 18.8 mmol) and PCl5 (4.79 g, 23.0 mmol) were mixed in POCI3 (6 mL). The reaction was stirred and refiuxed at 120 °C over night (15 h). Cooled to rt., diluted with CHCl3 (20 mL) and saturated with HCl (g). This gave a white precipitation, which was filtered off, washed with CHCl3 and dried under reduced pressure to give the title compound (3.36 g, 83percent) as a white powder. | |
81% | Reference Example 29 pyridin-3-ylsulfonyl chloride hydrochloride; A mixture of <strong>[636-73-7]3-pyridinesulfonic acid</strong> (50.0 g), phosphorus pentachloride (80.0 g) and phosphorus oxychloride (100 mL) was stirred at 120° C. for 8 hr. Under a nitrogen atmosphere, the mixture was cooled to room temperature, and chloroform (dehydrated, 330 mL) was added. Hydrogen chloride was blown in, and the precipitated crystals were collected by filtration and washed with chloroform (dehydrated) to give the title compound as a white solid (yield 54.7 g, 81percent). 1H-NMR (DMSO-d6) delta: 8.03-8.07 (1H, m), 8.68 (1H, d, J=8.1 Hz), 8.87 (1H, d, J=5.7 Hz), 9.01 (1H, s). | |
81% | With phosphorus pentachloride; trichlorophosphate; In chloroform; at 120℃; for 8h; | Reference Example 132 Pyridin-3-ylsulfonyl chloride hydrochloride A mixture of <strong>[636-73-7]3-pyridinesulfonic acid</strong> (50.0 g), phosphorus pentachloride (80.0 g) and phosphorus oxychloride (100 mL) was stirred at 120°C for 8 hr. Under a nitrogen atmosphere, the mixture was cooled to room temperature, and chloroform (dehydrated, 330 mL) was added. Hydrogen chloride was blown in, and the precipitated crystals were collected by filtration and washed with chloroform (dehydrated) to give the title compound as a white solid (yield 54.7 g, 81percent). 1H-NMR (DMSO-d6)delta: 8.03-8.07 (1H, m), 8.68 (1H, d, J=8.1 Hz), 8.87 (1H, d, J=5.7 Hz), 9.01 (1H, s). |
With phosphorus pentachloride; | EXAMPLE XIII Pyridine-3-sulphonic Acid Chloride Hydrochloride 1 g (6.3 mmol) of <strong>[636-73-7]pyridine-3-sulphonic acid</strong> and 1.4 g (6.7 mmol) of phosphorus pentachloride are stirred for 2 hours at 150° C. After cooling, excess phosphorus pentachloride is eliminated in vacuo. The crude product is further reacted immediately. Yield: 1.2 g (91percent of theory). | |
With phosphorus pentachloride; In chloroform; | EXAMPLE 9 N-[6-[4-(3-pyridinylsulfonylamino)phenyl]-1,2-dihydro-2-oxonicotinoyl]ampicillin A mixture of 34.0 g (0.21 mol) of <strong>[636-73-7]3-pyridinesulfonic acid</strong> and 47 g (0.24 mol) of phosphorus pentachloride is heated on the steam bath for 2 hrs and the phosphorus oxychloride is removed at reduced pressure to give an oil which crystallize upon addition of chloroform. The solid is filtered, washed with chloroform, and dried under high vacuum to give 38.2 g of 3-pyridinesulfonyl chloride hydrochloride. | |
With phosphorus pentachloride; trichlorophosphate; In chloroform; | Reference Example 132 Pyridin-3-ylsulfonyl chloride hydrochloride A mixture of <strong>[636-73-7]3-pyridinesulfonic acid</strong> (50.0 g), phosphorus pentachloride (80.0 g) and phosphorus oxychloride (100 mL) was stirred at 120°C for 8 hr. Under a nitrogen atmosphere, the mixture was cooled to room temperature, and chloroform (dehydrated, 330 mL) was added. Hydrogen chloride was blown in, and the precipitated crystals were collected by filtration and washed with chloroform (dehydrated) to give the title compound as a white solid (yield 54.7 g, 81percent). 1H-NMR (DMSO-d6)delta: 8.03-8.07 (1H, m), 8.68 (1H, d, J=8.1 Hz), 8.87 (1H, d, J=5.7 Hz), 9.01 (1H, s). | |
With phosphorus pentachloride; trichlorophosphate; at 130℃; for 3.5h; | Preparation 27; A mixture of <strong>[636-73-7]3-pyridinesulfonic acid</strong> (10.0 g), phosphorous pentachloride (13.1 g) and phosphoryl chloride (10.0 ml) was stirred at 1300C for 3.5 hours. The solution was evaporated and diluted with acetone. The solution was evaporated and poured into water (200 ml) and EPO <DP n="71"/>isopropyl ether (400 ml). The organic layer was separated, washed with brine twice, saturated sodium bicarbonate aqueous solution and brine and dried over magnesium sulfate. The solution was evaporated, covered with hexane (20 ml) and added hydrogen chloride in ethyl acetate (4N, 20 ml) dropwise with stirring. The resulting solid was collected by filtration and dried to give 3- pyridinesulfonyl chloride hydrochloride (9.49 g) .NMR (200 MHz, DMSO-d6, delta) : 8.12 (IH, dd, J=5, 8Hz), 8.72 (IH, dd, J=I.8, 3Hz), 8.95 (IH, d, J=5.5Hz),8.99 (IH, d, J=IHz), 14.25 (IH, br s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bromine; at 130℃; for 8h; | PREPARATION 14 5-amino-A/-methyl-3-pyridinesulfonamideStep 1 . 5-bromo-3-pyridinesulfonyl chlorideA mixture of 3-pyridinesulfonyl chloride hydrochloride (8.9 g, 44 mmol) and bromine (14 g, 88 mmol) was heated to 130 °C for 8 h. The mixture was cooled and used directly in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With 4-methyl-morpholine; In dichloromethane; at 80℃; for 0.416667h;Microwaves; | EXAMPLE 6 Compound 62: 1-[(Pyridin-3-yl)sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone 1-[(Pyridin-3-yl)sulfonylamino]-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone: 1-Amino-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone toluenesulfonic acid (0.3 g, 0.58 mmol) is stirred in dichloromethane (6 mL) and 3-pyridylsulfonylchloride HCl (135 mg, 0.63 mmol) is added followed by 4-methylmorpholine (0.2 mL). The mixture is heated in a microwave oven at 80° C. for 25 minutes. The mixture is evaporated and purified over silica (hexane/ethylacetate) to give the afford 0.12 g (41percent yield) of the desired product as a white solid. 1H NMR (DMSO-d6) delta 10.3 (s, 1H), 9.0 (s, 1H), 8.9 (d, J=6 Hz, 1H), 8.2 (d, J=7.8 Hz, 1H), 7.65 (m, 1H), 7.2 (d, J=7.8 Hz, 2H), 7.05, (d, J=7.8 Hz, 2H), 6.95 (d, J=7.8 Hz, 2H), 6.8 (d, J=7.8 Hz, 2H), 4.5 (t, J=7 Hz, 1H), 3.8 (s, 3H), 3.75 (s, 3H), 3.3 (m, 1H), 3.2 (m, 1H), 2.75 (m, 2H), 2.4 (m, 2H). Anal. calcd. for C24H26N4O5S: C, 59.74; H, 5.43; N, 11.61; found C, 59.60; H, 5.47; N, 11.37. FAB-HRMS calcd. 483.1702; found 483.1720 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate; In water; for 0.75h; | Intermediate 24; 4-Bromo-l-(pyridine-3-ylsulfonyl)-lH-indole; Aq. 2M NaOH (1 mL) was added to a stirred mixture of <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (240 mg, 1.12 mmol; Intermediate 23), 4-bromoindole (200 mg, 1.02 mmol) <n="84"/>and tetrabutylammonium hydrogen sulfate (35 mg, 0.10 mmol). The reaction was stirred 45 min. and the layers were allowed to separate. The organic layer was washed twice with diluted aq. NaOH, dried and concentrated to get the title compound (325 mg, 95%) as an off white solid. MS (ESI+) for CnH9BrN2O2S m/z 337 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4% | With sodium hydroxide; In dichloromethane; water; at 20℃; | Example 178; l-[5-Methoxy-l-(pyridin-3-ylsulfonyl)-lH-indol-4-yl]-lambda/,lambda/-dimethylmethanamine; To a solution of l-(5-methoxy-lH-indol-4-yl)-lambda/,lambda/-dimethylmethanamine (30 mg, 0.15 mmol; Intermediate 97) and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (43 mg, 0.20 mmol) in DCM (1 mL) 5 M NaOH (2 mL) was added. The reaction mixture was stirred at rt over night. The organic phase was collected and the solvent was removed under reduced pressure. Purification by preparative HPLC/UV (System B) afforded the title product (2 mg, 4percent) as a white solid. MS (ESI+) for Ci7Hi9N3O3S m/z 346 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; | 7-((4-Butyl-benzyl)-(Pyridine-3-sulfonyl)-amino)-heptanoic acid methyl ester. A solution of 7-(4-butyl-benzylamino)-heptanoic acid methyl ester prepared of Example 1, Step A (0.10 g, 0.33 mmol), N,N-diisopropylethylamine (0.85 g 0.66 mmol) and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong>, prepared of Preparation 2, (0.070 g, 0.33 mmol) in 3 mL CH2Cl2 was stirred at room temperature overnight. The mixture was diluted with CH2Cl2 and the organic solution was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The product was purified by flash chromatography on silica gel (10percent EtOAc/hexanes to 30percent EtOAc/hexanes) to afford the title compound of Step B. 1H NMR (400 MHz, CDCl3) delta 9.01 (s, 1H), 8.75 (d, 1H), 8.04 (d, 1H), 7.41 (dd, 1H), 7.23 (m, 4H), 4.30 (s, 2H), 3.62 (s, 3H), 3.08 (t, 2H), 2.55 (t, 2H), 2.19 (t, 2H), 1.10-1.58 (m, 12H), 0.87 (t, 3H); MS 447 (M+1). | |
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; | Step B: Amide Formation 7-((4-Butyl-benzyl)-(pyridine-3-sulfonyl)-amino)-heptanoic acid methyl ester. A solution of 7-(4-butyl-benzylamino)-heptanoic acid methyl ester prepared of Example 1, Step A (0.10 g, 0.33 mmol); N,N-diisopropylethylamine (0.85 g 0.66 mmol) and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong>, prepared of Preparation 2, (0.070 g, 0.33 mmol) in 3 mL CH2Cl2 was stirred at room temperature overnight. The mixture was diluted with CH2Cl2 and the organic solution was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The product was purified by flash chromatography on silica gel (10percent EtOAc/hexanes to 30percent EtOAc/hexanes) to afford the title compound of Step B. 1H NMR (400 MHz, CDCl3) delta 9.01 (s, 1H), 8.75 (d, 1H), 8.04 (d, 1H), 7.41 (dd, 1H), 7.23 (m, 4H), 4.30 (s, 2H), 3.62 (s, 3H), 3.08 (t, 2H), 2.55 (t, 2H), 2.19 (t, 2H), 1.10-1.58 (m, 12H), 0.87 (t, 3H); MS 447 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 0℃; for 2h; | {3-[(4-Tert-Butyl-benzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenoxy acetic acid tert-butyl ester. To a solution of {3-[(4-tert-butyl-benzylamino)-methyl]-phenoxy}acetic acid tert-butyl ester (10.0 g, 26.1 mmol), prepared in Step A, in CH2Cl2 (75 mL) at 0° C. was added triethylamine (8.0 mL, 57.4 mmol), and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (6.10 g, 28.7 mmol), of Preparation 2. The mixture was stirred for 0.5 h, the ice bath was removed, and the mixture was stirred for an additional 1.5 h. A 1:1 solution of water:aqueous saturated sodium bicarbonate was added to the solution, and the product was extracted into CH2Cl2 (3.x.). The combined organic solutions were dried over MgSO4 and concentrated in vacuo and the product was purified via silica gel chromatography (2:1 Hex:EtOAc) to give the title compound of Step B (11.0 g) as a clear oil. 1H NMR (400 MHz, CDCl3) delta 9.01 (s, 1H), 8.75 (d, 1H), 7.97 (d, 1H), 7.38 (m, 1H), 7.11-7.23 (m, 3H), 6.97 (d, 2H), 6.71 (d, 1H), 6.65 (d, 1H), 6.60 (s, 1H), 4.40 (s, 2H), 4.32 (s, 4H), 1.48 (s, 9H), 1.26 (s, 9H); MS 525 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 0 - 20℃; | Step A: Sulfonamide Formation 5-(3-((3-(3-Chloro-phenyl)-propyl)-(pyridine-3-sulfonyl)-amino)-propyl)-thiophene-2-carboxylic acid methyl ester. A solution of 5-(3-(3-(3-chloro-phenyl)-propylamino)-propyl)-thiophene-2-carboxylic acid methyl ester (from Preparation 8, 0.0855 g, 0.243 mmol), triethylamine (0.0541 g 0.534 mmol), and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (from Preparation 2, 0.0572 g, 0.267 mmol) in 10 mL CH2Cl2 combined at 0° C. was stirred at room temperature overnight. The organic solution was washed with water, saturated NaHCO3 and brine, dried over MgSO4, filtered and concentrated in vacuo to afford the title compound of Step A as an oil. MS 494 (M+1). | |
With triethylamine; In dichloromethane; | 5-(3-((3-(3-Chloro-phenyl)-propyl)-(pyridine-3-sulfonyl)-amino)-propyl)-thiophene-2-carboxylic acid methyl ester A solution of 5-(3-(3-(3-chloro-phenyl)-propylamino)-propyl)-thiophene-2-carboxylic acid methyl ester (from Preparation 8, 0.0855 g, 0.243 mmol), triethylamine (0.0541 g 0.534 mmol), and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (from Preparation 2, 0.0572 g, 0.267 mmol) in 10 mL CH2Cl2 combined at 0° C. was stirred at room temperature overnight. The organic solution was washed with water, saturated NaHCO3 and brine, dried over MgSO4, filtered and concentrated in vacuo to afford the title compound of Step A as an oil. MS 494 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; water; | Step D {3-[(Pyridine-3-sulfonylamino)-methyl]-phenoxy}-acetic acid tert-butyl ester. To a solution of (3-aminomethyl-phenoxy)-acetic acid tert-butyl ester (296 mg, 1.25 mmol) in CH2Cl2 at 0° C. was added <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (279 mg, 1.31 mmol) followed by Et3N (0.36 mL, 2.6 mmol). The reaction was stirred at room temperature for 24 h and was quenched with a 1:1 solution of water and saturated aqueous NaHCO3. The aqueous solution was washed with CH2Cl2 (3*). The combined organic solutions were dried (MgSO4), filtered, and concentrated. Medium pressure chromatography (1:1 hexanes:EtOAc) provided the title compound as a white solid (369.5 mg). 1H NMR (400 MHz, CDCl3) delta 9.04 (s, 1H), 8.75 (m, 1H), 8.09 (d, 1H), 7.44 (m, 1H), 7.15 (m, 1H), 6.76 (m, 3H), 5.23 (bs, 1H), 4.44 (s, 2H), 4.16 (d, 2H), 1.47 (s, 9H); MS 379 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7-[(4-Pyrazin-2-yl-benzyl)-(pyridine-3-sulfonyl)-amino]-heptanoic acid methyl ester The title compound of Step A was prepared from 7-(4-pyrazin-2-yl-benzylamino)-heptanoic acid methyl ester, of Step A, and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong>, of Preparation 2, following the method of Exmaple 1, Step B. 1H NMR (400 MHz, CDCl3) delta 9.04 (d, 1H), 8.99 (d, 1H), 8.78 (m, 1H), 8.60 (dd, 1H), 8.49 (d, 1H), 8.08 (m, 1H), 7.95 (m, 2H), 7.46-7.39 (m, 3H), 4.40 (s, 2H), 3.60 (s, 3H), 3.14 (t, 2H), 2.18 (t, 2H), 1.45 (m, 2H), 1.36 (m, 2H), 1.12 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | In dichloromethane; sodium hydrogencarbonate; | a 5-Methyl-3-(3-pyridinylsulfonyloxy)phenol A mixture of <strong>[6153-39-5]orcinol monohydrate</strong> (1.42 g, 0.01 mol) and 3-pyridylsulfonyl chloride hydrochloride (2.13 g, 0.01 mol), as prepared in J. Am. Chem. Soc., 114:4889 (1992), in saturated aqueous sodium bicarbonate (17.5 mL) and dichloromethane (50 mL) was stirred rapidly at ambient temperature for 2 days. The dichloromethane was separated and the aqueous layer was extracted with ethyl acetate (3*25 mL). The ethyl acetate and dichloromethane extracts were combined and washed with brine, dried over anhydrous sodium sulfate, and evaporated to dryness. The residue was recrystallized from ether and hexane, collected by filtration, and dried under high vacuum to give 1.54 g of a white solid (58percent yield). 1 H-NMR (300 MHz, CDCl3) delta 9.03 (d, 1H), 8.88 (dd, 1H), 8.16 (dt, 1H), 7.5 (m, 1H), 6.57 (d, 1H), 6.42 (s, 1H), 6.32 (t, 1H), 2.24 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trichlorophosphate; | PREPARATION 1 Pyridine-3-sulfonyl chloride hydrochloride A mixture of <strong>[636-73-7]pyridine-3-sulfonic acid</strong> (15.0 g), phosphorous pentachloride (24.0 g) and phosphorous oxychloride (30 mL) was heated to 120° C. for 16 h. The reaction was cooled to room temperature, and the resulting suspension was saturated with HCl (g). A white precipitate was collected, washed with CHCl3, and dried in vacuo to afford the title compound (15.6 g). 1 H NMR (400 MHz, DMSO) delta 8.98 (s, 1H), 8.85 (d, 1H), 8.66 (d, 1H), 8.02 (t, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
662 mg (83.5%) | With pyridine; In water; toluene; | REFERENCE EXAMPLE 1 N-(2-Methoxyphenyl)-3-pyridinesulfonamide o-Anisidine (377 mg, 3.0 mmol) was dissolved in toluene (10 ml) to which were subsequently added pyridine (0.48 ml, 6.0 mmol) and <strong>[42899-76-3]3-pyridinesulfonylchloride hydrochloride</strong> (642 mg, 3.0 mmol) at room temperature. After 1.5 hours of stirring at 100° C., the resulting reaction solution was mixed with water (20 ml), adjusted to pH 7 to 8 with anhydrous sodium carbonate, extracted with ethyl acetate and then washed with water and saturated brine. After drying on anhydrous sodium carbonate and removing the solvent by evaporation, the resulting orange solid was purified by a silica gel column chromatography (ether:hexane=3:1) to obtain a light orange solid which was subsequently washed with an ether-hexane (1:3) mixture solution to obtain 662 mg (83.5percent) of the title compound in the form of colorless prism crystals. Melting point: 101.5°-103° C. IR (KBr): 3008, 2712, 1586, 1498, 1420, 1336, 1320, 1280, 1256, 1194, 1110, 1020, 762, 744, 600, 578, 544 cm-1 NMR (CDCl3) delta: 3.58 (3H, s), 6.71 (1H, dd, J=7.5 Hz, 2 Hz), 6.80-7.14 (3H, m) 7.31 (1H, dd, J=8 Hz, 5 Hz), 7.54 (1H, dd, J=7.5 Hz, 2 Hz), 7.96 (1H, dd, J=8 Hz, 2 Hz), 8.70 (1H, dd, J=5 Hz, 2 Hz), 8.93 (1H, d, J=2 Hz) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With sodium hydrogencarbonate; In dichloromethane; water; at 20℃; for 48h; | a) 5-Methyl-3-(3-pyridinylsulfoxy)phenol A mixture of orcinol monohydrate (1.42 g, 0.01 mol) and 3-pyridylsulfonyl chloride hydrochloride (2.13 g, 0.01 mol), as prepared in J. Am. Chem. Soc., 114:4889 (1992), in saturated aqueous sodium bicarbonate (17.5 mL) and dichloromethane (50 mL) was stirred rapidly at ambient temperature for 2 days. The dichloromethane was separated and the aqueous layer was extracted with ethyl acetate (3 x 25 mL). The ethyl acetate and dichloromethane extracts were combined and washed with brine, dried over anhydrous sodium sulfate, and evaporated to dryness. The residue was recrystallized from ether and hexane, collected by filtration, and dried under high vacuum to give 1.54 g of a white solid (58percent yield). 1H-NMR (300 MHz, CDCl3) delta 9.03 (d, 1 H), 8.88 (dd, 1 H), 8.16 (dt, 1 H), 7.5 (m, 1 H), 6.57 (d, 1 H), 6.42 (s, 1 H), 6.32 (t, 1 H), 2.24 (s, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | Reference Example 44 ethyl 5-bromo-2-methyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carboxylate; Ethyl 5-bromo-2-methyl-1H-pyrrole-3-carboxylate (2.26 g) was dissolved in tetrahydrofuran (100 mL), sodium hydride (60percent in oil, 1.16 g) was added and the mixture was stirred at room temperature for 15 min. 15-Crown-5 (5.90 mL) was added and the mixture was further stirred at the same temperature for 15 min. 3-Pyridinesulfonyl chloride hydrochloride (3.13 g) was added and the reaction mixture was stirred at room temperature for 1 hr. Saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1-->7:3) to give the title compound as a yellow oil (yield 2.31 g, 64percent). 1H-NMR (CDCl3) delta: 1.24-1.34 (3H, m), 2.94 (3H, s), 4.23-4.30 (2H, m), 6.69 (1H, s), 7.51-7.55 (1H, m), 8.17-8.21 (1H, m), 8.88-8.91 (1H, m), 9.14 (1H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Reference Example 55 5-phenyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; Under an argon atmosphere, 5-phenyl-1H-pyrrole-3-20 carbaldehyde (342 mg) was dissolved in absolute tetrahydrofuran (20 mL) and sodium hydride (60percent in oil, 240 mg) was added while stirring at room temperature. After stirring at the same temperature for 15 min, 15-crown-5 (1.21 mL) was added, and the mixture was further stirred at the same temperature for 15 min. Pyridin-3-ylsulfonyl chloride hydrochloride (642 mg) was added, and the mixture was further stirred at the same temperature for 30 min. The reaction mixture was diluted with ethyl acetate, washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1-->1:1) to give the title compound as a brown solid (yield 470 mg, 75percent). 1H-NMR (CDCl3) delta: 6.60 (1H, d, J=1.8 Hz), 7.15-7.19 (2H, m), 7.25-7.37 (3H, m), 7.42-7.48 (1H, m), 7.53-7.57 (1H, m), 8.13 (1H, d, J=1.8 Hz), 8.49-8.50 (1H, m), 8.74-8.76 (1H, m), 9.90 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Reference Example 63 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; To a solution (96 mL) of 5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde (475 mg) in tetrahydrofuran was added sodium hydride (60percent in oil, 503 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (2.77 g) was added dropwise and the mixture was stirred for 30 min. Pyridine-3-sulfonyl chloride hydrochloride (1.35 g) was added, and the mixture was further stirred for 3 hr. The reaction mixture was diluted with saturated brine, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:3-->2:3) and crystallized from diisopropyl ether-ethyl acetate (4:1) to give the title compound as colorless crystals (yield 680 mg, 82percent). 1H-NMR (CDCl3) delta: 6.68 (1H, d, J=1.8 Hz), 6.99-7.05 (1H, m), 7.16-7.19 (2H, m), 7.35-7.39 (1H, m), 7.45-7.51 (1H, m), 7.69-7.73 (1H, m), 8.14 (1H, d, J=1.8 Hz), 8.58-8.59 (1H, m), 8.81-8.83 (1H, m), 9.91 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
~ 100% | Reference Example 64 1-(pyridin-3-ylsulfonyl)-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carbaldehyde; To a solution (36 mL) of 5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carbaldehyde (240 mg) in tetrahydrofuran was added sodium hydride (60percent in oil, 201 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (1.11 g) was added dropwise and the mixture was stirred for 30 min. Pyridine-3-sulfonyl chloride hydrochloride (537 mg) was added, and the mixture was further stirred for 3 hr. The reaction mixture was diluted with saturated brine, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=4:1-->2:3) and crystallized from diisopropyl ether to give the title compound as colorless crystals (yield 380 mg, about 100percent). 1H-NMR (CDCl3) delta: 6.69 (1H, d, J=11.8 Hz), 7.34-7.38 (1H, m), 7.44-7.48 (1H, m), 7.61-7.69 (4H, m), 8.16 (1H, d, J=1.8 Hz), 8.45 (1H, d, J=2.4 Hz), 8.81 (1H, m), 9.91 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Reference Example 65 4-methyl-5-phenyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; 4-Methyl-5-phenyl-1H-pyrrole-3-carbaldehyde (185 mg) was dissolved in tetrahydrofuran (10 mL), sodium hydride (60percent in oil, 60 mg) was added and the mixture was stirred at room temperature for 15 min. 15-Crown-5 (0.30 mL) was added and the mixture was further stirred at the same temperature for 15 min. 3-Pyridinesulfonyl chloride hydrochloride (231 mg) was added and the reaction mixture was stirred at room temperature for 1 hr. Water was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1-->1:1) to give the title compound as a colorless solid (yield 172 mg, 53percent). 1H-NMR (CDCl3) delta: 2.03 (3H, s), 7.01-7.04 (2H, m), 7.26-7.55 (5H, m), 8.07 (1H, s), 8.47 (1H, m), 8.75-8.78 (1H, m), 9.97 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With ammonia; In methanol; dichloromethane; at 20℃; for 0.833333h; | Example 79; N-(6-(2-(pyridine-5-sulfonamido)pyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide; Step 1. Pyridine-3 -sulfonamide; Pyridine-3-sulfonyl chloride HCl (647.2 mg, 3.023 mmol) was suspended in DCM (9.0 mL) and NH3 (5 mL, 7N in MeOH, 35 mmol) was added. The reaction was stirred at RT under nitrogen for 50 minutes and then filtered, and the solid was washed with DCM. The filtrate was concentrated and dried under high vacuum to provide pyridine-3 -sulfonamide (477 mg , 91percent yield). MS (ESI pos. ion) m/z: 159(MH+). Calculated exact mass for C5H6N2O2S: 158. |
With ammonia; In acetone; at 0 - 20℃; for 3h; | Preparation 28; To a suspension of <strong>[42899-76-3]3-pyridinesulfonyl chloride hydrochloride</strong> (5.00 g) in acetone (8.5 ml) was added ammonia aqueous solution (28percent, 8.5 ml) at 00C dropwise and stirred at room temperature for 3 hours. The solution was evaporated and poured into water (ca. 10 ml), ethyl acetate (100 ml) and tetrahydrofuran (100 ml). The organic layer was washed with brine twice and the aqueous layer was extracted with ethyl acetate (90 ml) and methanol (10 ml). The combined organic layer was dried over magnesium sulfate, evaporated and crystallized in hexane and ethyl acetate to give 3-pyridinesulfonamide (3.45 g) .(+)ESI-MS (m/z): 159 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With chloro-trimethyl-silane; triethylamine; In methanol; dichloromethane; water; | A suspension of 11.5 g (50 mmol) of 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid, 21 ml (150 mmol) of triethylamine, and 500 ml of dichloromethane is stirred at 0°-5° and 20.2 ml (158 mmol) of chlorotrimethylsilane is added. The ice bath is removed and the mixture is stirred at room temperature for 1 hr. The solution is cooled with an ice bath and 11.8 g (55 mmol) of <strong>[42899-76-3]3-pyridinesulfonyl chloride hydrochloride</strong> is added followed by 7 ml (50 mmol) of triethylamine 15 min later. The reaction is stirred at room temperature for 70 hrs, cooled with an ice bath and 3.5 ml (25 mmol) of triethylamine is added. The reaction is stirred at room temperature for 4.5 hrs, cooled with an ice bath, and 11.8 g (55 mmol) of <strong>[42899-76-3]3-pyridinesulfonyl chloride hydrochloride</strong> is added. The mixture is stirred at room temperature for 16 hrs and the dichloromethane is evaporated. Water is added to the residue and the precipitated solid is filtered, washed with water, ether, methanol, and ether, and dried to give 18.8 g of product. This material is combined with 3.2 g from another run and is heated with stirring at reflux for 1.5 hr with 450 ml of methanol. The solid is filtered, washed with methanol and ether and dried to give 19.8 g of 6-[4-(3-pyridinylsulfonylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid; mp>260°. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; potassium carbonate; In water; | EXAMPLE 10 N-[6-[3-(3-pyridinylsulfonylamino)phenyl]-1,2-dihydro-2-oxonicotinoyl]ampicillin A suspension of 11.5 g (50 mmol) of 6-(3-aminophenyl)-1,2-dihydro-2-oxonicotinic acid and 300 ml of water is stirred at room temperature and 21 g (0.15 mol) of potassium carbonate is added. The solution is cooled to 25° and 13.0 g (61 mmol) of <strong>[42899-76-3]3-pyridinesulfonyl chloride hydrochloride</strong> is slowly added. The solution is clarified by filtration and the pH of the filtrate adjusted to 5.3 with hydrochloric acid. The precipitated solid is filtered, washed with water and dissolved in 300 ml of water containing 10 g (72 mmol) of potassium carbonate. The solution is stirred at room temperature and 10 g (47 mmol) of <strong>[42899-76-3]3-pyridinesulfonyl chloride hydrochloride</strong> is gradually added along with portions of potassium carbonate to maintain a pH of 8. Altogether 10 g (72 mmol) of potassium carbonate is added. The reaction is stirred for 30 min at room temperature and filtered. The pH of the filtrate is adjusted to 6 with hydrochloric acid and the solids filtered and washed with water. A second crop is obtained by lowering the pH of the filtrate to 4.0 and the solid is filtered. The two crops are combined with 200 ml of 1 N sodium hydroxide and heated on the steam bath for 1 hour and filtered. The filtrate is acidified to pH 5.7 with 1 N hydrochloric acid and the solid is filtered, washed with water, methanol, and ether and dried under high vacuum to give 15.2 g of 6-[3-(3-pyridinylsulfonylamino)phenyl]-1,2-dihydro-2-oxonicotinic acid; mp 305° dec. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.18g (0.02 mol) of pyridine-3-sulphonic acid (C5H5NSO3) was mixed with 8.34g (0.04 mol) of PCl5in a dry flask. The flask was protected from moisture and heated at 130-140°C under reflux with stirring for 2 hours. The reaction mixture was then cooled. The cold solidified reaction mixture was then triturated with CHCl3to remove PCl5and POCl3. The supernatant liquid was discarded. The triturating process was repeated using fresh CHCl3and the product was finally triturated with CHCl3saturated with hydrogen chloride. The hydrogen chloride was prepared by the slow addition of concentrated sulphuric acid (H2SO4) from a dropping funnel to sodium chloride in a round bottom flask. The round bottom flask was connected to the trituration reaction vessel by rubber tubing. A white powder formed, which was filtered, washed with CHCl3and finally dried in a vacuum. This process gave 3-pyridinesulphonylchloride-HCl (yield 3.05g, 85 percent) C5H4NSO2Cl, (Melting point: 141-143°C). This procedure is described by Reinhart F. E., J. Franklin. Ind. 236, 316-320 (1943). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37.0% | In pyridine; acetone; | Example 10 (I13) A solution of <strong>[42899-76-3]pyridine-3-sulphonyl chloride hydrochloride</strong> (83.0 g; 0.31 mol) in pyridine (40 ml) was added dropwise to a solution of anthranilic acid (21.0 g; 0.153 mol) in pyridine (45 ml) at 45-55°C over a 1.5 hour period. The resulting reaction mixture was stirred at 50-60°C for a further 2 hours, and then for 18 hours at 15-20°C. Acetone (45 ml) was added and the precipitate was isolated by filtration. The solid was washed well with acetone (2 x 50 ml), 2M hydrochloric acid (50 ml), water (to pH 7) and finally acetone again (2 x 50 ml). Drying in vacuo gave the product as a pale-yellow solid (11.8 g). The material was crystallized from an ethyl acetate/dichloromethane mixture to give 2-[2-(3-pyridylsulphonylamino)phenyl]-4H-3,1-benzoxazin-4-one (10.8 g; 37.0percent yield; HPLC analysis 99.4percent w/w) as a pale-yellow powder. m.p. 221-222°C. I.R. (KBr disc): numax= 1760, 1600, 1245, 1155 and 760 cmmin1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | Reference Example 130 5-(2,6-difluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; To a solution of 5-(2,6-difluorophenyl)-1H-pyrrole-3-carbaldehyde (420 mg) in tetrahydrofuran (42 mL) was added sodium hydride (60percent in oil, 244 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (1.34 g) was added dropwise and the mixture was stirred for 30 min. 3-Pyridylsulfonyl chloride hydrochloride (565 mg) was added, and the mixture was further stirred for 1 hr. The reaction mixture was diluted with saturated brine, and the mixture was extracted with ethyl acetate. The obtained extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:3-->1:1), and crystallized from diisopropyl ether to give the title compound as colorless crystals (yield 590 mg, 84percent). 1H-NMR (CDCl3) delta: 6.76 (1H, d, J=1.9 Hz), 6.90-6.95 (2H, m), 7.40-7.52 (2H, m), 7.77-7.81 (1H, m), 8.18 (1H, d, J=1.9 Hz), 8.65-8.66 (1H, m), 8.85-8.87 (1H, m), 9.91 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Reference Example 131 5-(4-cyclohexylphenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; Sodium hydride (60percent in oil, 68 mg) was added to a solution of 5-(4-cyclohexylphenyl)-1H-pyrrole-3-carbaldehyde (0.17 g) in tetrahydrofuran (12 mL) at room temperature. The mixture was stirred for 20 min, 3-pyridinesulfonyl chloride (0.19 g) was added, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was poured into ice water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=3:2-->42:1) to give the title compound as crystals (yield 0.26 g, 97percent). 1H-NMR (CDCl3) delta: 1.21-1.53 (5H, m), 1.73-1.98 (5H, m), 2.50-2.60 (1H, m), 6.57 (1H, d, J=1.9 Hz), 7.03-7.09 (2H, m), 7.13-7.29 (3H, m), 7.48 (1H, ddd, J=8.3, 2.0, 1.9 Hz), 8.11 (1H, d, J=1.9 Hz), 8.49 (1H, d, J=2.3 Hz), 8.73 (1H, dd, J=4.8, 1.6 Hz), 9.89 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Reference Example 136 5-(2-methylphenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; To a solution of 5-(2-methylphenyl)-1H-pyrrole-3-carbaldehyde (371 mg) in tetrahydrofuran (10 mL) were added sodium hydride (60percent in oil, 288 mg) and 15-crown-5 (1.32 g) at room temperature. After stirring for 5 min, a suspension of <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (642 mg) in N,N-dimethylformamide (5 mL) was added at the same temperature. After stirring for 15 min, ice water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=6:1-->3:1) to give the title compound as a red oil (yield 521 mg, 80percent). 1H-NMR (CDCl3) delta: 1.82 (3H, s), 6.56 (1H, d, J=1.5 Hz), 6.87-6.90 (1H, m), 7.11-7.19 (2H, m), 7.30-7.39 (2H, m), 7.56-7.60 (1H, m), 8.15 (1H, d, J=1.5 Hz), 8.52-8.53 (1H, m), 8.80-8.82 (1H, m), 9.92 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | Reference Example 138 4-fluoro-5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; Sodium hydride (60percent in oil, 0.25 g) was washed twice with hexane and suspended in tetrahydrofuran (10 mL). A solution (5 mL) of 4-fluoro-5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde (0.43 g) in tetrahydrofuran was added at 0° C., and the mixture was stirred at the same temperature for 30 min. 15-Crown-5 (1.3 mL) and <strong>[42899-76-3]3-pyridinesulfonyl chloride hydrochloride</strong> (0.68 g) were added at 0° C., and the mixture was stirred at the same temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=1:1) to give the title compound as pale-yellow crystals (yield 0.55 g, 76percent). 1H-NMR (CDCl3) delta: 7.02-7.08 (1H, m), 7.20-7.31 (2H, m), 7.36-7.41 (1H, m), 7.48-7.55 (1H, m), 7.67-7.71 (1H, m), 8.00 (1H, d, J=5.1 Hz), 8.55-8.56 (1H, m), 8.83-8.85 (1H, m), 9.93 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | Reference Example 139 4-fluoro-5-(2-methylphenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; Sodium hydride (60percent in oil, 0.11 g) was washed twice with hexane and suspended in tetrahydrofuran (10 mL). A solution (5 mL) of 4-fluoro-5-(2-methylphenyl)-1H-pyrrole-3-carbaldehyde (0.45 g) in tetrahydrofuran was added at 0° C., and the mixture was stirred at the same temperature for 15 min. A solution (2 mL) of 15-crown-5 (0.56 mL) and 3-pyridinesulfonyl chloride (0.44 g) in tetrahydrofuran was added at 0° C., and the mixture was stirred at the same temperature for 30 min. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=1:1) to give the title compound as pale-yellow crystals (yield 0.59 g, 77percent). 1H-NMR (CDCl3) delta: 1.77 (3H, s), 7.02-7.04 (1H, m), 7.17-7.23 (2H, m), 7.29-7.34 (1H, m), 7.37-7.42 (1H, m), 7.54-7.58 (1H, m), 8.00 (1H, d, J=4.5 Hz), 8.49-8.50 (1H, m), 8.81-8.83 (1H, m), 9.92 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | Reference Example 153 5-mesityl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; To a solution of 5-mesityl-1H-pyrrole-3-carbaldehyde (0.36 g) in tetrahydrofuran (20 mL) was added sodium hydride (60percent in oil, 0.14 g) under ice-cooling, and the mixture was stirred at room temperature for 0.5 hr. A solution of 15-crown-5 (0.75 g) in tetrahydrofuran (3 mL) was added and, after stirring for 5 min, pyridin-3-ylsulfonyl chloride (0.45 g) was added under ice-cooling. The reaction mixture was stirred at room temperature for 0.5 hr, a saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=10:1-->2:1) to give the title compound as a pale-brown amorphous form (yield 0.38 g, 62percent). 1H-NMR (CDCl3) delta: 1.63 (6H, s), 2.35 (3H, s), 6.48 (1H, d, J=1.5 Hz), 6.83 (2H, s), 7.26-7.35 (1H, m), 7.60-7.64 (1H, m), 8.17 (1H, dd, J=1.5, 0.9 Hz), 8.56 (1H, d, J=2.1 Hz), 8.83 (1H, dd, J=4.5, 1.5 Hz), 9.90 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Reference Example 158 5-(2-fluorophenyl)-4-iodo-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; To a solution (42 mL) of 5-(2-fluorophenyl)-4-iodo-1H-pyrrole-3-carbaldehyde (400 mg) in tetrahydrofuran was added sodium hydride (60percent in oil, 102 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (560 mg) was added dropwise and the mixture was stirred for 30 min. Pyridin-3-ylsulfonyl chloride (340 mg) was added, and the mixture was further stirred for 1 hr. The reaction mixture was diluted with saturated brine and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=3:2-->1:1) and crystallized from diisopropyl ether to give the title compound as colorless crystals (yield 540 mg, 93percent). 1H-NMR (CDCl3) delta: 7.01-7.07 (1H, m), 7.12-7.17 (1H, m), 7.23-7.28 (1H, m), 7.37-7.41 (1H, m), 7.50-7.58 (1H, m), 7.69-7.73 (1H, m), 8.21 (1H, s), 8.54-8.54 (1H, m), 8.85 (1H, dd, J=4.9, 1.5 Hz), 9.85 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | Reference Example 159 5-(2,6-dimethylphenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; A mixture of 5-bromo-1H-pyrrole-3-carbaldehyde (0.87 g), 2,6-dimethylphenylboronic acid (4.50 g), cesium carbonate (13.0 g), tri-tert-butylphosphine (0.10 g), tris(dibenzylideneacetone)dipalladium (0) (0.23 g) and mesitylene (200 mL) was stirred with heating under reflux for 5 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=3:1) to give a brown oil (0.48 g). To a solution of the oil in tetrahydrofuran (20 mL) was added sodium hydride (60percent in oil, 0.19 g) under ice-cooling, and the mixture was stirred at room temperature for 0.5 hr. A solution of 15-crown-5 (1.06 g) in tetrahydrofuran (3 mL) was added, and the mixture was stirred for 5 min. Pyridin-3-ylsulfonyl chloride (0.64 g) was added under ice-cooling. The reaction mixture was stirred at room temperature for 0.5 hr, a saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=2:1) to give the title compound as a pale-brown oil (yield 0.42 g, 25percent). 1H-NMR (CDCl3) delta: 1.66 (6H, s), 6.52 (1H, d, J=2.1 Hz), 6.70 (2H, d, J=7.5 Hz), 7.25-7.34 (2H, m), 7.56-7.60 (1H, m), 8.19 (1H, d, J=1.5 Hz), 8.53 (1H, d, J=1.8 Hz), 8.81-8.83 (1H, m), 9.91 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Reference Example 192 4-chloro-5-(2-fluoropyridin-3-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; To a solution (20 mL) of 4-chloro-5-(2-fluoropyridin-3-yl)-1H-pyrrole-3-carbaldehyde (270 mg) in tetrahydrofuran was added sodium hydride (60percent in oil, 100 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (530 mg) was added dropwise and the mixture was stirred for 30 min. 3-Pyridylsulfonyl chloride (321 mg) was added, and the mixture was further stirred for 1 hr. The reaction mixture was diluted with saturated brine, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=1:11-->1:4), and crystallized from diethyl ether to give the title compound as colorless crystals (yield 358 mg, 81percent). 1H-NMR (CDCl3) delta: 7.35-7.39 (1H, m), 7.42-7.46 (1H, m), 7.69-7.73 (1H, m), 7.76-7.82 (1H, m), 8.14 (1H, s), 8.39-8.41 (1H, m), 8.64 (1H, dd, J=2.5 Hz, 0.6 Hz), 8.89 (1H, dd, J=4.8 Hz, 1.6 Hz), 9.97 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With 15-crown-5; sodium hydride; In N,N-dimethyl-formamide; at 0℃; for 2h; | Reference Example 74 tert-butyl[5-bromo-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate; To a suspension (10 mL) of sodium hydride (60percent in oil, 204 mg) in tetrahydrofuran was added a solution (3 mL) of tert-butyl[(5-bromo-1H-pyrrol-3-yl)methyl]methylcarbamate (410 mg) in N,N-dimethylformamide at 0° C., and 15-crown-5 (938 mg) and <strong>[42899-76-3]pyridin-3-ylsulfonyl chloride hydrochloride</strong> (456 mg) were added at the same temperature. After stirring at room temperature for 2 hr, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=8:1-->3:1) to give the title compound as a pale-yellow powder (yield 522 mg, 85percent). 1H-NMR (CDCl3) delta: 1.47 (9H, s), 2.80 (3H, brs), 4.18 (2H, brs), 6.28 (1H, brs), 7.35 (1H, brs), 7.48-7.52 (1H, m), 8.18-8.22 (1H, m), 8.85-8.88 (1H, m), 9.12-9.13 (1H, m). |
85% | With 15-crown-5; sodium hydride; In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil; at 0 - 35℃; for 2h; | Reference Example 293 tert-Butyl [5-bromo-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate A solution (3 mL) of tert-butyl [(5-bromo-1H-pyrrol-3-yl)methyl]methylcarbamate (410 mg) in N,N-dimethylformamide was added to a suspension (10 mL) of sodium hydride (60percent in oil, 204 mg) in tetrahydrofuran at 0°C, 15-crown-5 (938 mg) and <strong>[42899-76-3]pyridin-3-ylsulfonyl chloride hydrochloride</strong> (456 mg) were added at the same temperature. After stirring at room temperature for 2 hr, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=8:1?3:1) to give the title compound as a pale-yellow powder (yield 522 mg, 85percent). 1H-NMR (CDCl3)delta: 1.47 (9H, s), 2.80 (3H, brs), 4.18 (2H, brs), 6.28 (1H, brs), 7.35 (1H, brs), 7.48-7.52 (1H, m), 8.18-8.22 (1H, m), 8.85-8.88 (1H, m), 9.12-9.13 (1H, m). |
In tetrahydrofuran; water; N,N-dimethyl-formamide; | Reference Example 293 tert-Butyl [5-bromo-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate A solution (3 mL) of tert-butyl [(5-bromo-1H-pyrrol-3-yl)methyl]methylcarbamate (410 mg) in N,N-dimethylformamide was added to a suspension (10 mL) of sodium hydride (60percent in oil, 204 mg) in tetrahydrofuran at 0°C, 15-crown-5 (938 mg) and <strong>[42899-76-3]pyridin-3-ylsulfonyl chloride hydrochloride</strong> (456 mg) were added at the same temperature. After stirring at room temperature for 2 hr, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=8:1-->3:1) to give the title compound as a pale-yellow powder (yield 522 mg, 85percent). 1H-NMR (CDCl3)delta: 1.47 (9H, s), 2.80 (3H, brs), 4.18 (2H, brs), 6.28 (1H, brs), 7.35 (1H, brs), 7.48-7.52 (1H, m), 8.18-8.22 (1H, m), 8.85-8.88 (1H, m), 9.12-9.13 (1H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With 15-crown-5; sodium hydride; In tetrahydrofuran; at 0 - 10℃; for 0.25h; | Reference Example 136 5-(2-methylphenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; To a solution of 5-(2-methylphenyl)-1H-pyrrole-3-carbaldehyde (371 mg) in tetrahydrofuran (10 mL) were added sodium hydride (60percent in oil, 288 mg) and 15-crown-5 (1.32 g) at room temperature. After stirring for 5 min, a suspension of <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (642 mg) in N,N-dimethylformamide (5 mL) was added at the same temperature. After stirring for 15 min, ice water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=6:1-->3:1) to give the title compound as a red oil (yield 521 mg, 80percent). 1H-NMR (CDCl3) delta: 1.82 (3H, s), 6.56 (1H, d, J=1.5 Hz), 6.87-6.90 (1H, m), 7.11-7.19 (2H, m), 7.30-7.39 (2H, m), 7.56-7.60 (1H, m), 8.15 (1H, d, J=1.5 Hz), 8.52-8.53 (1H, m), 8.80-8.82 (1H, m), 9.92 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With 15-crown-5; sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 2h; | Reference Example 154 5-[2-(methylthio)phenyl]-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde; To a suspension of sodium hydride (60percent in oil, 40 mg) in tetrahydrofuran (3 mL) were added a solution of 5-[2-(methylthio)phenyl]-1H-pyrrole-3-carbaldehyde (150 mg) in tetrahydrofuran (5 mL), 15-crown-5 (182 mg) and pyridin-3-ylsulfonyl chloride (135 mg) under ice-cooling. After stirring at room temperature for 2 hr, water was added and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=4:1-->2:1) to give the title compound as colorless crystals (yield 170 mg, 69percent). 1H-NMR (CDCl3) delta: 2.05 (3H, s), 6.68 (1H, d, J=2.1 Hz), 6.97-6.99 (1H, m), 7.17-7.31 (3H, m), 7.40-7.45 (1H, m), 7.65-7.70 (1H, m), 8.16 (1H, d, J=2.1 Hz), 8.45-8.46 (1H, m), 8.75-8.77 (1H, m), 9.90 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; | Reference Example 148 Ethyl 5-bromo-2-methyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carboxylate Ethyl 5-bromo-2-methyl-1H-pyrrole-3-carboxylate (2.26 g) was dissolved in tetrahydrofuran (100 mL), sodium hydride (60percent in oil, 1.16 g) was added and the mixture was stirred at room temperature for 15 min. 15-Crown-5 (5.90 mL) was added and the mixture was further stirred at the same temperature for 15 min, and <strong>[42899-76-3]3-pyridinesulfonyl chloride hydrochloride</strong> (3.13 g) was added. The reaction mixture was stirred at room temperature for 1 hr, saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1-->7:3) to give the title compound as a yellow oil (yield 2.31 g, 64percent). 1H-NMR (CDCl3)delta: 1.24-1.34 (3H, m), 2.94 (3H, s), 4.23-4.30 (2H, m), 6.69 (1H, s), 7.51-7.55 (1H,-m), 8.17-8.21 (1H, m), 8.88-8.91 (1H, m), 9.14 (1H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Reference Example 234 5-Phenyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde Under an argon atmosphere, 5-phenyl-1H-pyrrole-3-carbaldehyde (342 mg) was dissolved in absolute tetrahydrofuran (20 mL) and sodium hydride (60percent in oil, 240 mg) was added while stirring at room temperature. After stirring at the same temperature for 15 min, 15-crown-5 (1.21 mL) was added, and the mixture was further stirred at the same temperature for 15 min. Pyridin-3-ylsulfonyl chloride hydrochloride (642 mg) was added, and the mixture was further stirred at the same temperature for 30 min. The reaction mixture was diluted with ethyl acetate, washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1?1:1) to give the title compound as a brown solid (yield 470 mg, 75percent). 1H-NMR (CDCl3)delta: 6.60 (1H, d, J=1.8 Hz), 7.15-7.19 (2H, m), 7.25-7.37 (3H, m), 7.42-7.48 (1H, m), 7.53-7.57 (1H, m), 8.13 (1H, d, J=1.8 Hz), 8.49-8.50 (1H, m), 8.74-8.76 (1H, m), 9.90 (1H, s). | |
In tetrahydrofuran; | Reference Example 234 5-Phenyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde Under an argon atmosphere, 5-phenyl-1H-pyrrole-3-carbaldehyde (342 mg) was dissolved in absolute tetrahydrofuran (20 mL) and sodium hydride (60percent in oil, 240 mg) was added while stirring at room temperature. After stirring at the same temperature for 15 min, 15-crown-5 (1.21 mL) was added, and the mixture was further stirred at the same temperature for 15 min. Pyridin-3-ylsulfonyl chloride hydrochloride (642 mg) was added, and the mixture was further stirred at the same temperature for 30 min. The reaction mixture was diluted with ethyl acetate, washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1-->1:1) to give the title compound as a brown solid (yield 470 mg, 75percent). 1H-NMR (CDCl3)delta: 6.60 (1H, d, J=1.8 Hz), 7.15-7.19 (2H, m), 7.25-7.37 (3H, m), 7.42-7.48 (1H, m), 7.53-7.57 (1H, m), 8.13 (1H, d, J=1.8 Hz), 8.49-8.50 (1H, m), 8.74-8.76 (1H, m), 9.90 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Reference Example 256 4-Methyl-5-phenyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde 4-Methyl-5-phenyl-1H-pyrrole-3-carbaldehyde (185 mg) was dissolved in tetrahydrofuran (10 mL), sodium hydride (60percent in oil, 60 mg) was added and the mixture was stirred at room temperature for 15 min. 15-Crown-5 (0.30 mL) was added and the mixture was further stirred at the same temperature for 15 min. 3-Pyridinesulfonyl chloride hydrochloride (231 mg) was added and the reaction mixture was stirred at room temperature for 1 hr. Water was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1?1:1) to give the title compound as a colorless solid (yield 172 mg, 53percent). 1H-NMR (CDCl3)delta: 2.03 (3H, s), 7.01-7.04 (2H, m), 7.26-7.55 (5H, m), 8.07 (1H, s), 8.47 (1H, m), 8.75-8.78 (1H, m), 9.97 (1H, s). | |
In tetrahydrofuran; water; | Reference Example 256 4-Methyl-5-phenyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde 4-Methyl-5-phenyl-1H-pyrrole-3-carbaldehyde (185 mg) was dissolved in tetrahydrofuran (10 mL), sodium hydride (60percent in oil, 60 mg) was added and the mixture was stirred at room temperature for 15 min. 15-Crown-5 (0.30 mL) was added and the mixture was further stirred at the same temperature for 15 min. 3-Pyridinesulfonyl chloride hydrochloride (231 mg) was added and the reaction mixture was stirred at room temperature for 1 hr. Water was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1-->1:1) to give the title compound as a colorless solid (yield 172 mg, 53percent). 1H-NMR (CDCl3)delta: 2.03 (3H, s), 7.01-7.04 (2H, m), 7.26-7.55 (5H, m), 8.07 (1H, s), 8.47 (1H, m), 8.75-8.78 (1H, m), 9.97 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Reference Example 146 Methyl 5-bromo-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carboxylate Sodium hydride (60percent in oil, 1.60 g) was washed twice with hexane and suspended in tetrahydrofuran (20 mL). Under ice-cooling, a solution (10 mL) of methyl 5-bromo-1H-pyrrole-3-carboxylate (2.67 g) in tetrahydrofuran was added dropwise, and the mixture was stirred at the same temperature for 10 min. 15-Crown-5 (8.83 g) and <strong>[42899-76-3]pyridin-3-ylsulfonyl chloride hydrochloride</strong> (4.21 g) were added to the reaction mixture, and the mixture was further stirred at room temperature for 12 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-hexane to give the title compound as white crystals (yield 4.21 g, 93percent). 1H-NMR (CDCl3)delta: 3.84 (3H, s), 6.72 (1H, d, J=1.8 Hz), 7.51-7.56 (1H, m), 8.08 (1H, d, J=1.8 Hz), 8.22-8.26 (1H, m), 8.90-8.92 (1H, m), 9.20-9.21 (1H, m). | |
In tetrahydrofuran; water; | Reference Example 146 Methyl 5-bromo-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carboxylate Sodium hydride (60percent in oil, 1.60 g) was washed twice with hexane and suspended in tetrahydrofuran (20 mL). Under ice-cooling, a solution (10 mL) of methyl 5-bromo-1H-pyrrole-3-carboxylate (2.67 g) in tetrahydrofuran was added dropwise, and the mixture was stirred at the same temperature for 10 min. 15-Crown-5 (8.83 g) and <strong>[42899-76-3]pyridin-3-ylsulfonyl chloride hydrochloride</strong> (4.21 g) were added to the reaction mixture, and the mixture was further stirred at room temperature for 12 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-hexane to give the title compound as white crystals (yield 4.21 g, 93percent). 1H-NMR (CDCl3)delta: 3.84 (3H, s), 6.72 (1H, d, J=1.8 Hz), 7.51-7.56 (1H, m), 8.08 (1H, d, J=1.8 Hz), 8.22-8.26 (1H, m), 8.90-8.92 (1H, m), 9.20-9.21 (1H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Reference Example 245 5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde To a solution (96 mL) of <strong>[881674-56-2]5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde</strong> (475 mg) in tetrahydrofuran was added sodium hydride (60percent in oil, 503 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (2.77 g) was added dropwise and the mixture was stirred for 30 min, pyridine-3-sulfonyl chloride hydrochloride (1.35 g) was added, and the mixture was further stirred for 3 hr. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:3?2:3), and crystallized from diisopropyl ether-ethyl acetate (4:1) to give the title compound as colorless crystals (yield 680 mg, 82percent). 1H-NMR (CDCl3)delta: 6.68 (1H, d, J=1.8 Hz), 6.99-7.05 (1H, m), 7.16-7.19 (2H, m), 7.35-7.39 (1H, m), 7.45-7.51 (1H, m), 7.69-7.73 (1H, m), 8.14 (1H, d, J=1.8 Hz), 8.58-8.59 (1H, m), 8.81-8.83 (1H, m), 9.91 (1H, s). | |
78% | A total of 0.5g, 4-dimethylaminopyridine 90mg, 5ml acetonitrile, take N, N-diisopropylethylamine1.5g with a small amount of acetonitrile dissolved in the above reaction bottle, take pyridine-3-sulfonyl chloride hydrochloride 1.1g, with 5mlAcetonitrile dissolved into the reaction flask, heated to 45 ° C stirring reaction 5h after cooling to room temperature, adding 5ml of water,The pH was adjusted to 5 with 0.5 N hydrochloric acid solution, and 20 ml of water was slowly added dropwise (at this time, a large amount of white solid precipitated)Stirring at room temperature for 0.5h, cooling to below 10 , stirring 1h, filtration, filter cake with a small amount of acetonitrile and water mixtureWashing, 50 ° C drying was V total of 0.69g, yield 78percent. | |
In tetrahydrofuran; | Reference Example 245 5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde To a solution (96 mL) of <strong>[881674-56-2]5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde</strong> (475 mg) in tetrahydrofuran was added sodium hydride (60percent in oil, 503 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (2.77 g) was added dropwise and the mixture was stirred for 30 min, pyridine-3-sulfonyl chloride hydrochloride (1.35 g) was added, and the mixture was further stirred for 3 hr. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=7:3-->2:3), and crystallized from diisopropyl ether-ethyl acetate (4:1) to give the title compound as colorless crystals (yield 680 mg, 82percent). 1H-NMR (CDCl3)delta: 6.68 (1H, d, J=1.8 Hz), 6.99-7.05 (1H, m), 7.16-7.19 (2H, m), 7.35-7.39 (1H, m), 7.45-7.51 (1H, m), 7.69-7.73 (1H, m), 8.14 (1H, d, J=1.8 Hz), 8.58-8.59 (1H, m), 8.81-8.83 (1H, m), 9.91 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Ca. 100% | Reference Example 247 1-(Pyridin-3-ylsulfonyl)-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carbaldehyde To a solution (36 mL) of 5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carbaldehyde (240 mg) in tetrahydrofuran was added sodium hydride (60percent in oil, 201 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (1.11 g) was added dropwise and the mixture was stirred for 30 min. Pyridine-3-sulfonyl chloride hydrochloride (537 mg) was added, and the mixture was further stirred for 3 hr. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=4:1?2:3) and crystallized from diisopropyl ether to give the title compound as colorless crystals (yield 380 mg, about 100percent). 1H-NMR (CDCl3)delta: 6.69 (1H, d, J=1.8 Hz), 7.34-7.38 (1H, m), 7.44-7.48 (1H, m), 7.61-7.69 (4H, m), 8.16 (1H, d, J=1.8 Hz), 8.45 (1H, d, J=2.4 Hz), 8.81 (1H, m), 9.91 (1H, s). | |
In tetrahydrofuran; | Reference Example 247 1-(Pyridin-3-ylsulfonyl)-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carbaldehyde To a solution (36 mL) of 5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carbaldehyde (240 mg) in tetrahydrofuran was added sodium hydride (60percent in oil, 201 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (1.11 g) was added dropwise and the mixture was stirred for 30 min. Pyridine-3-sulfonyl chloride hydrochloride (537 mg) was added, and the mixture was further stirred for 3 hr. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=4:1-->2:3) and crystallized from diisopropyl ether to give the title compound as colorless crystals (yield 380 mg, about 100percent). 1H-NMR (CDCl3)delta: 6.69 (1H, d, J=1.8 Hz), 7.34-7.38 (1H, m), 7.44-7.48 (1H, m), 7.61-7.69 (4H, m), 8.16 (1H, d, J=1.8 Hz), 8.45 (1H, d, J=2.4 Hz), 8.81 (1H, m), 9.91 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Reference Example 311 tert-Butyl [5-(2,4-difluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate By a similar operation as in Reference Example 146 and using tert-butyl [5-(2,4-difluorophenyl)-1H-pyrrol-3-yl]methyl}methylcarbamate (113 mg), sodium hydride (60percent in oil, 51 mg), 15-crown-5 (0.21 mL) and <strong>[42899-76-3]pyridin-3-ylsulfonyl chloride hydrochloride</strong> (113 mg), the title compound was obtained as a pale-yellow oil (yield 110 mg, 68percent). 1H-NMR (CDCl3)delta: 1.46 (9H, s), 2.82 (3H, brs), 4.24 (2H, brs), 6.19 (1H, br), 6.77-6.92 (2H, m), 7.11-7.19 (1H, m), 7.33-7.37 (2H, m), 7.68-7.72 (1H, m), 8.62 (1H, d, J=2.4 Hz), 8.77-8.79 (1H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Reference Example 312 tert-Butyl [5-(2,5-difluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate By a similar operation as in Reference Example 146 and using tert-butyl [5-(2,5-difluorophenyl)-1H-pyrrol-3-yl]methyl}methylcarbamate (135 mg), sodium hydride (60percent in oil, 60 mg), 15-crown-5 (0.25 mL) and <strong>[42899-76-3]pyridin-3-ylsulfonyl chloride hydrochloride</strong> (135 mg), the title compound was obtained as a colorless oil (yield 105 mg, 54percent). 1H-NMR (CDCl3)delta: 1.50 (9H, s), 2.82 (3H, s), 4.23 (2H, brs), 6.24 (1H, br), 6.89-7.13 (4H, m), 7.33-7.39 (2H, m), 7.71-7.75 (1H, m), 8.67 (1H, d, J=2.4 Hz), 8.78-8.80 (1H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Reference Example 313 tert-Butyl [5-(4-chloro-2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate By a similar operation as in Reference Example 146 and using tert-butyl [5-(4-chloro-2-fluorophenyl)-1H-pyrrol-3-yl]methyl}methylcarbamate (127 mg), sodium hydride (60percent in oil, 54 mg), 15-crown-5 (0.22 mL) and <strong>[42899-76-3]pyridin-3-ylsulfonyl chloride hydrochloride</strong> (120 mg), the title compound was obtained as a colorless oil (yield 103 mg, 57percent). 1H-NMR (CDCl3)delta: 1.46 (9H, s), 2.81 (3H, s), 4.23 (2H, brs), 6.21 (1H, brs), 7.08-7.15 (4H, m), 7.32-7.38 (2H, m), 7.69-7.73 (1H, m), 8.64 (1H, d, J=2.4 Hz), 8.77-8.79 (1H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With dmap; triethylamine; In dichloromethane; N,N-dimethyl-formamide; | Combine 4-(6-nitro-lNo.-indol-3-yl)-benzonitrile, 9, (290 mg, 1.1 mmol), 4- dimethylaminopyridine (14mg, 0.11 mmol), triethyl amine (740 muL, 5.3 mmol), methylene chloride (7.0 mL) and dimethylformamide (2.5 mL) in a 25 mL flask. Add 3-pyridine sulfonyl chloride hydrochloride (283 mg, 1.32 mmol). Let the solution stir overnight. Isolate the precipitate by filtration and wash the precipitate 3x with methylene chloride to yield 251 mg, 0.62 mmol, 56percent of the title compound. LRMS (API ES+) = 405.0 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With triethylamine; In water; acetonitrile; | Example 236 6-(Pyridine-3-sulfonylamino)hexanoic acid methyl ester (93c) Pyridine-3-sulfonyl chloride hydrochloride (92c) (1.8 g, 5.0 mmol) was added to a solution of methyl 6-aminohexanoate hydrochloride (91) (1.82 g, 10 mmol) and triethylamine (3.03 g, 30 mmol) in acetonitrile (30 ml). The mixture was stirred for 1 hour at ambient temperature, filtered and solvents were removed under reduced pressure. The oily product was dissolved in water (15 ml) and extracted with ethyl ether (50 ml). The extract was dried (Na2SO4) and the solvents were removed under reduced pressure. The title compound (1.09 g, 76percent) was obtained as oil and was used for the next step without an additional purification. 1H NMR deltaH (90 MHz, DMSO-d6) delta: 0.80-1.51 (6H, m, CH2); 1.83 (2H, t, J=6.5 Hz, CH2); 2.76 (2H, t, J=6.5 Hz, CH2N); 3.58 (3H, s, CH3); 7.54 (1H, dd, J=5.0 Hz, J=8.2 Hz, C5HN 8.12 (1H, dt, J=2.0 Hz, J=8.2 Hz, C5HN); 8.61 (1H, dd, J=2.0 Hz, J=5.0 Hz, C5HN); 8.81 (1H, d, J=2.0 Hz, C5HN). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.9% | In chlorobenzene; at 85℃; under 172.517 Torr; | 21.4 g (0.100 mol) of <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> and 42.8 g of monochlorobenzene were placed in a 200 mL four-necked flask, and the slurry Liquid). The internal pressure was adjusted to 23 kPa using a vacuum pump and heated to 85 ± 5 ° C. for 5 hours (dehydrochlorination). After 5 hours, the contents of the flavor became almost transparent liquid. Thereafter, monochlorobenzene was distilled off under reduced pressure (100 ° C., 27 kPa). Subsequently, distillation under reduced pressure (110 ° C., 1 kPa) gave 16.5 g (0.0929 mol, yield 92.9percent) of pyridine-3-sulfonyl chloride. |
With sodium hydrogencarbonate; In dichloromethane; water; | Preparation of the free base: Pyridine-3-sulfonyl chloride hydrochloride (20 mg, 0.093 mmol) was dissolved in a mixture of dichloromethane and aqueous saturated NaHCO3 and the organic layer was dried (MgSO4) and evaporated to give pyridine-3-sulfonyl chloride. tert-Buty\\ 10-chloro-l,3,4,8-tetrahydro-2H-[l,4]oxazepino[6,7-e]indole-2- carboxylate (Intermediate 20, 10 mg, 0.031 mmol) was dissolved in DMF (1 mL) and sodium hydride (60percent in mineral oil, 2.5 mg, 0.062 mmol) was added. The mixture was stirred for 10 minutes before pyridine-3-sulfonyl chloride (0.093 mmol) in DMF (1 mL) was added. The reaction mixture was stirred at room temperature for 10 minutes before TFA (2 mL) was added and the mixture was heated at 50 0C overnight. The reaction mixture was evaporated and the crude material was purified by preparative HPLC (ACE C8, 0.1percent TFA - CH3CN) to give the title compound as a white solid (2.6 mg) in the form of the trifluoroacetate salt. MS m/z 364 [M + H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate; In dichloromethane; water; at 20℃; for 5h; | To a solution of toer/-butyl l-methyl-l,3,4,8-tetrahydro-2H-[l,4]oxazepino[6,7-e]indole- 2-carboxylate (Intermediate 42, 0.030 g (0,098 mmol) in DCM (2 mL), tetrabutyl ammonium hydrogensulphate, (6.4 mg, 0.020 mmol), 2 M NaOH (0.2 mL, 0.4 mmol) and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (35 mg, 0.20 mmol) were added. The EPO <DP n="109"/>reaction mixture was stirred vigoruosly at room temperature for one hour. More 2 M NaOH (1 mL, 2 mmol) was added to the mixture, followed by the sulfonyl chloride (17 mg, 0.10 mmol) every hour for four hours (a total of 103 mg). Water (10 mL) was added and the aqueous phase was washed with CHCl3 (2x) and the combined organics were evaporated under reduced pressure. To the resulting oil was added TFA/DCM 50/50 (1 mL) and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure and the material was purified by preparative HPLC (ACE C8, 0.1percent TFA - CH3CN) to give the title compound (7.4 mg) in the form of the bis(trifluoroacetate) salt. MS m/z 344 [M + H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With triethylamine; In dichloromethane; at 20℃; for 17h; | Example 11; To a suspension of <strong>[42899-76-3]pyridine-3-sulfonylchloride hydrochloride</strong> (94 mg, 0.44 mmol) and N-[(lS)-l-(3-aminophenyl)ethyl]-6-chloropyrazin-2 -amine (100 mg, 0.4 mmol) in dichloromethane (5 mL) was added triethylamine (0.17 mL, 1.2 mmol) dropwise at room temperature and the mixture was stirred for 17 hours. After this time the mixture was diluted with ethyl acetate (20 mL), washed successively with saturated aqueous sodium hydrogen carbonate (2 x 20 mL) and brine (20 mL), dried (Na2SO4) and concentrated under reduced pressure to give a yellow oil which was purified by flash chromatography <n="97"/>(silica, ethyl acetate/hexanes) to giveN-(3-{(lS)-l-[(6-chloropyrazin-2-yl)amino]ethyl}phenyl)pyridine-3-sulfonamide (44 mg, 28percent) as a pale yellow foam. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 74; l-(Pyridin-3-ylsulfonyl)-3,4,5,6-tetrahydro-lH-azepino[5,4,3-alpha/] indole bis(trifluoroacetate)To a solution of tert-butyl l,3,4,6-tetrahydro-5H-azepino[5,4,3-cT]indole-5-carboxylate, Intermediate 12 (25 mg, 0.092 mmol) in DCM (2 mL) were added tetrabutylammonium hydrogensulfate (6.4 mg, 0.02 mmol), 2M NaOH (0.2 mL) and pyridine-3-sulfonyl chloride * HCl (33 mg, 0.18 mmol). The reaction mixture was vigoruosly stirred at room temperature for one hour. More 2M NaOH (1 mL) was added to the mixture, followed by half an equivalent of the sulphonyl chloride every hour for four hours. Water (10 mL) was added and the aqueous phase was washed twice with CetaCI3 and the combined organic phases were evaporated at reduced pressure. To the resulting oil was added TFA/DCM 50/50 (1 mL) and the mixture was stirred at room temperature over night. The solvent was removed at reduced pressure and the crude was purified with preparative HPLC (ACE C8 5 mm, water containing 0.1percent TFA - CH3CN) to give 4.6 mg of the title compound. MS (ESI) m/z 314 [M + H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In 1,2-dichloro-ethane; at 20℃; | Example 6; To a solution of Example 5 (16 mg, 0.042 mmol) in 1 ,2- dichloroethane (2 mL) was added diisopropylethyl amine (6.4 mg, 0.050 mmol) and 3-pyridine sulfonyl chloride hydrochloride (Combi-Blocks, San Diego, CA) (11 mg, 0.050 mmol). The resultant solution was stirred at RT overnight. The solution was diluted with CH2CI2, washed with water, dried over Na2SO4, filtered and concentrated. The crude material was purified via preparative thin layer chromatography (SiO2: 1 :1 hexanes: EtOAc ) to afford Example 6 (9mg) as a clear oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | Reference Example 12 2-phenyl-1-(pyridin-3-ylsulfonyl)-1H-imidazole-4-carbaldehyde To a solution of 2-phenyl-1H-imidazole-4-carbaldehyde (1.00 g) in tetrahydrofuran (50 mL) was added sodium hydride (60percent in oil, 697 mg) at room temperature, and the mixture was stirred for 30 min. 15-Crown-5 (3.84 g) was added dropwise, and the mixture was further stirred for 10 min. 3-Pyridylsulfonyl chloride hydrochloride (1.62 g) was added to the reaction mixture, and the mixture was stirred for 2 hr. Saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=3:2-->2:3), and the obtained oil was crystallized from diisopropyl ether to give the title compound as colorless crystals (yield 754 mg, 41percent). 1H-NMR (CDCl3) delta: 7.29-7.33 (1H, m), 7.37-7.45 (4H, m), 7.53-7.64 (2H, m), 8.33 (1H, s), 8.56 (1H, d, J=2.4 Hz), 8.79 (1H, dd, J=4.9, 1.5 Hz), 9.95 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 20.8h; | Compound Il (48.00 g, 101 mmol, 1.0 equiv) was free-based by partitioning between dichloromethane (360 mL) and 1 M aqueous sodium bicarbonate (240 mL). The layers were separated and the organic layer washed once with water (240 mL). The layers were separated and N,N-diisopropylethylamine (53.4 mL, 304 mmol, 3.0 equiv) was added to the organic layer. Pyridine-3-sulfonyl chloride hydrochloride (III) (26.4 g, 123 mmol, 1.2 equiv) and dichloromethane (240 mL) were charged to a separate reaction vessel and cooled to O0C under nitrogen atmosphere. The free base/N,N- diisopropylethylamine solution was added over 1.8 hours. The reaction mixture was warmed to room temperature and held for 19 hours, at which point formation of intermediate of formula IV ((3-[(4-tert-Butyl-benzyl)-(pyridine-3-sulfonyl)-amino]- <n="15"/>methyl}-phenoxy)-acetic acid ethyl ester) was complete. The reaction mixture was washed with 1 N hydrochloric acid (336 ml_), then with 1 M aqueous sodium bicarbonate (336 ml_). 2B ethanol (384 mL) was added to the organic layer, and the mixture was atmospherically distilled until the pot volume was about 400 mL. 6N sodium hydroxide (19.9 mL, 119 mmol, 1.2 equiv) was added and the mixture was held at room temperature for 19 hours. Concentrated hydrochloric acid (11.0 mL, 134 mmol, 1.3 equiv) was added followed by water (192 mL). The slurry granulated 5 hours at room temperature and was filtered. The solids were washed with 50:50 2B ethanohwater (144 mL), water (144 mL), 2B ethanol (144 mL), then dried to afford compound V (34.78 g, 73percent yield), mp = 159-16O0C. Anal Calcd for C25H28N2O5S: C 64.08; H 6.02; N 5.98. Found C 64.13; H 6.11; N 5.99. 1H NMR (400 MHz, DMSO- dbeta): delta 1.21 (s, 9H), 4.31 (s, 2H), 4.33 (s, 2H), 4.54 (s, 2H), 6.65-6.69 (m, 1H), 6.71- 6.74 (m, 1H), 6.75-6.76 (m, 1H), 7.01 (d, 2H, J=8.1 Hz), 7.13 (t, 1H, J=7.9Hz), 7.21 (d, 2H, J=8.3Hz), 7.56-7.59 (m, 1H), 8.16-8.19 (m, 1 H), 8.80-8.82 (m, 1H), 8.97-8.98 (m, 1H), 13.04 (br s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With triethylamine; In dichloromethane; at 20℃; for 0.333333h;Product distribution / selectivity; | Add triethylamine (0.426 mL, 3.058 mmol) to a stirring solution of [2-(3'-chloro- 2,3,5,6-tetrahydro-[l,2']bipyrazinyl-4-yl)-ethyl]-methyl-amine (0.200 g, 0.612 mmol) in dichloromethane (5 mL). Add <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> salt (0.157 g, 0.734 mmol) at room temperature. Stir at room temperature for 20 min. Dilute with dichloromethane and saturated aqueous sodium bicarbonate. Separate and extract the aqueous fraction with dichloromethane. Combine the organic fractions, dry over sodium sulfate, filter, and concentrate. Purify the resulting material by silica gel chromatography eluting with hexanes: acetone 4: 1 to afford the title preparation (0.220 g, 91percent yield). MS ES: m/z = 397 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | Example 30 [3'-[(pyridine-3-ylsulfonyl)(methyl)amino]methyl}-5-(trifluoromethyl)biphenyl-2-yl]oxy} acetic acid (34)To a solution of amine 17 (0.033 g; 0.08 mmol) in anhydrous DCM (1 mL) was added DIEA (100 ?L; 0.57 mmol; 7 eq) and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (30 ?L, 0.12 mmol, 1.5 eq). The reaction was stirred at RT for 16h, the solvent was evaporated, and the residue was purified by silica gel chromatography (linear gradient of 0percent EtOAC/hexanes to 100percent EtOAC). The purified ester was treated directly with 30percent TFA/DCM for 2h. The solvent was evaporated and the residue was purified by reverse phase preparative HPLC to give 21 mg (55percent) of 34. 1HNMR (CDCl3, 300 MHz): ? 9.05 (bs, IH), 8.82 (bs, IH), 8.19 (d, J= 8.1Hz, IH), 7.56 (m, 4H), 7.40 (m, 2H), 7.28 (d, J = 7.2 Hz, IH), 6.96(d, J = 9.3 Hz, IH), 4.70 (s, 2H), 4.28 (s, 2H), 2.73 (s, 3H) MS (ESI): MH+ = 481.0 HPLC (ZQ) tR = 8.18 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; | Pyridine-3-sulfonic acid {6-[7-(2,2-dimethyl-propionyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-1H-indol-4-yl}-amide. Substituting pyridine-3-sulfonic acid (6-bromo-1H-indol-4-yl)-amide (prepared by treatment of <strong>[350800-81-6]6-bromo-1H-indol-4-ylamine</strong> with 3-pyridinesulfonyl chloride, HCl salt in pyridine) for 6-bromo-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one. MP=305-307 C, (M+H)+=475. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With dmap; In tetrahydrofuran; at 20℃; for 72h; | A solution of 2-({1-[1-(4-chlorophenyl)cyclopropyl]-3,4-dihydroisoquinolin-7- yl}oxy)ethanamine (free base, 63 mg, 0.18 mmol), 4-N,N-Dimethylaminopyridin (47 mg, 0.39 mmol), 3-(chlorosulfonyl)pyridiniumchloride in tetrahydrofuran (THF, 10 ml) was stirred at room temperature for 3 days. The solvent was removed, the residue dissolved in ethyl acetate and extracted with water. The ethyl acetate was evaporated and the oily residue purified by chromatography. Yield: 46 mg (0.09 mmol, 52percent). ESI-MS [M+H+] = 482 CaIc. for C25H24CIN3O3S = 481 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11% | With sodium carbonate; In water; at 20℃; | Example 1:5:; Pyridine-3-sulfonyl chloride hydrochloride (1.71 g, 8 mmol) was added in small portions to a mixture of compound VII (0.544 g, 2 mmol) and sodium carbonate (aq, sat, 20 mL) and stirred at rt until nearly no monosulfonylation product was detected by LC-MS. The precipitate was collected and washed with water and MeOH and dried . After recrystallization from DMAc and MeOH, the title compound was obtained. Yield 130 mg (11percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With pyridine; at 80℃; for 12h; | Example 4. Synthesis of N-(4-oxo-2-(2-(trifluoromethyl)phenyl)-4H-chromen-8- yl)pyridine-3-sulfonamide (Compound 326):Pyridine- 3 -sulfonyl chloride hydrochloride 12 (280 mg, 1.3 mmol) was added to a solution of 8-amino-2-(2-(trifluoromethyl)phenyl)-4H-chromen-4-one 11 (100 mg, 0.328 mmol) in pyridine (5 mL). The reaction mixture was heated at 8O0C for 12 h. The pyridine was removed en vacuo. The residue was taken up in CH2Cl2, washed with sat. aq NaHCO3, dried (MgSO4) and concentrated. The crude residue was purified by MPLC eluting with CH2Cl2MeOH (0-10percent) followed by recrystallization from CH3CN to give Compound 326 (46 mg, 31 percent yield). MS (ESI) calcd for C2IHi3F3N2O4S: 446.1; found: 447 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | Reference Example 148 Ethyl 5-bromo-2-methyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carboxylate Ethyl 5-bromo-2-methyl-1H-pyrrole-3-carboxylate (2.26 g) was dissolved in tetrahydrofuran (100 mL), sodium hydride (60percent in oil, 1.16 g) was added and the mixture was stirred at room temperature for 15 min. 15-Crown-5 (5.90 mL) was added and the mixture was further stirred at the same temperature for 15 min, and <strong>[42899-76-3]3-pyridinesulfonyl chloride hydrochloride</strong> (3.13 g) was added. The reaction mixture was stirred at room temperature for 1 hr, saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1?7:3) to give the title compound as a yellow oil (yield 2.31 g, 64percent). 1H-NMR (CDCl3)delta: 1.24-1.34 (3H, m), 2.94 (3H, s), 4.23-4.30 (2H, m), 6.69 (1H, s), 7.51-7.55 (1H, m), 8.17-8.21 (1H, m), 8.88-8.91 (1H, m), 9.14 (1H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; for 16h; | Compound 50[00339] Pyridine-3-sulfonyl chloride hydrochloride (26.37mg, 0.12mmol, leq.) was added to a solution of Intermediate 32 (50mg, 0.12mmol, leq.) in pyridine (ImI) and the reaction stirred for 16h. The solvent was removed in vacuo and the residue purified by preparative HPLC to afford the title compound 50 (40mg, 59percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | With triethylamine; In dichloromethane; at 20℃; | EXAMPLE 62-(6-chloropyridin-3-yl)-4-(propan-2-yloxy)-6-(pyridin-3-ylsulfonyl)-5,6,7,8-tetrahydropyrido- [4,3-d]pyrimidine (L-I)TEA (0.022 mL, 0.159 mmol) was added to a suspension of J-3 (15 mg, 0.04 mmol) and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (10.2 mg, 0.048 mmol) in CH2Cl2 (0.5 ml) and stirred at room temperature over the weekend. The reaction mixture was partitioned between EtOAc (5 mL) and H2O (5 mL), and extracted with EtOAc (2x 5 mL). The organic phase was dried over Na2SO4, filtered and concentrated in vacuo. The resulting residue was purified by preperative TLC isocratic elution (100percent EtOAc) to afford the title compound (2.4 mg, 13percent) as a white solid. Data for L-I: 1H NMR (500 MHz, CDCl3) delta 9.32 (d, J= 2.4 Hz, IH), 9.13 (s, IH), 8.86 (m, IH), 8.57 (dd, J= 8.6, 2.4 Hz, IH), 8.18 (m, IH), 7.54 (dd, J= 7.8, 4.6 Hz, IH), 7.40 (d, J= 8.3, IH), 5.55 (hept, J= 6.2 Hz, IH), 4.22 (s, 2H), 3.54 (t, J= 5.5, 2H), 3.04 (t, J=5.5 Hz, 2H), 1.44 (d, J= 6.2 Hz, 6H); HRMS m/z (M+H) 446.1045 found, 446.1048 required. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50.4% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 7h;Inert atmosphere; | To a mixture of rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (30.2 mg, 0.071 mmol) in CH2Cl2 (3 mL) was added DIPEA (29.7 mg, 0.230 mmol) and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (22.8 mg, 0.106 mmol, Acme Bioscience). It was stirred at rt for 3 hrs under argon. More DIPEA (29.7 mg, 0.230 mmol) and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (Acme Bioscience, 25.2 mg, 0.118 mmol) were added. After 4 hrs the reaction mixture was extracted with EtOAc, washed with water, saturated sodium bicarbonate, water, and saturated NaCl. The organic phase was separated, and dried over Na2SO4. The reaction mixture was then purified by flash column to give rac (2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-1-(pyridine-3-sulfonyl)-pyrrolidine-3-carbonitrile (20.3 mg, 50.4percent). HRMS (ES+) m/z Calcd for C27H25Cl2F2N3O2S+H [(M+H)+]: 564.1086; Found: 564.1087. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water; at 0 - 20℃; | Step 2. 5-bromo-A/-methyl-3-pyridinesulfonamideTo CH3NH2 (50 mL of a 23-30 weight percent in H20) at 0 °C, was added 5-bromo- 3-pyridinesulfonyl chloride (44 mmol). The mixture was then warmed to rt and stirred for 3 h. The mixture was then extracted with EtOAc and concentrated in vacuo. The crude material was combined with that from an additional experiment (10 mmol scale) run under identical conditions and washed with 10:1 hot petroleum ether/EtOAc to afford 5-bromo-/V- methyl-3-pyridinesulfonamide (2.4 g, 18percent combined yield over two steps). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 77 (S)-N-(4-(3-fluoro-4-(trifluoromethoxy)phenyl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-yl)pyridine-3-sulfonamide 2,2,2-trifluoroacetate To a solution of (S)-4-(3-fluoro-4-(trifluoromethoxy)phenyl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-amine hydrochloride (0.030 g, 0.082 mmol) in DCM (0.5 mL) were added 3-pyridinesulfonylchloride HCl (0.015 mL, 0.099 mmol) and TEA (0.034 mL, 0.247 mmol). The resulting mixture was stirred at room temperature for 18 h. The mixture was filtered and the filtrate was purified by preparative HPLC (0-100percent MeCN 0.1percent TFA/H2O 0.1percent TFA) to give the title compound as a yellow solid. MS (ESI, positive ion) m/z: 470 (MH+). 1H NMR (400 MHz, d4-MeOH) delta: 8.70 (d, J=1.8 Hz, 1H), 8.62 (dd, J=5.0, 1.5 Hz, 1H), 7.97-8.07 (m, 2H), 7.44 (dd, J=8.0, 4.9 Hz, 1H), 7.30-7.38 (m, 2H), 7.16-7.29 (m, 3H), 4.34-4.46 (m, 1H), 3.97-4.13 (m, 1H), 2.73-3.01 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; at 20℃; for 1h; | To a solution of 5-chloro-3-methoxypyridin-2-amine (100 mg, 0.631 mmol) in pyridine (1 mL) <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (135 mg, 0.631 mmol) was added and the solution was stirred at room temperature for lhr. The pyridine was evaporated, DCM was added (5 mL) followed by 1M BBr3 in DCM (0.95 mL, 0.95 mmol) and the solution was stirred overnight. Saturated NaHC03 (5 mL) and more DCM (30 mL) were added. The phases were separated and the organic phase was washed with brine (2 mL), dried ( a2S04), the mixture was filtered and the filtrate evaporated to dryness to afford an orange oil which was chromatographed on silica (eluent: heptane: EtOAc 2: 1 then EtOAc:MeOH 9: 1) to afford the product as a green oil. Further purification was achieved using automated reverse phase HPLC (high pH method) to afford N-(5-chloro-3- hydroxypyridin-2-yl) pyridine-3 -sulfonamide as a brown solid (29 mg, 16percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With pyridine; at 20℃; | General procedure: The amino phenyl derivative (0.4 mmol, 1 equiv) was dissolvedin pyridine absolute (3 mL) and was spiked with sulfonyl chloride/acid chloride (1.5 equiv). The reaction mixture was stirred overnightat rt (refluxed in case of amide coupling). The reaction wasquenched by adding 10 mL of 2 N HCl and extracted with ethylacetate (3 50 mL). The organic layers werewashed with saturatedNaHCO3 (50 mL) and brine (50 mL), dried over magnesium sulfate,filtered and concentrated to dryness. The product was purified byCC. The title compound was prepared by reaction of (5-(3-aminophenyl)thiophene-2-yl)(2,6-difluoro-3-hydroxyphenyl)methanone (30)(100 mg, 0.30 mmol) and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (96 mg, 0.45mmol) according to Method C. The product was purified by CC (dichloromethane/methanol95:5); yield: 35percent (50 mg). 1H NMR (500 MHz, acetone-d6) delta8.28 (dd, J = 2.4, 0.8 Hz, 1H), 8.10 (dd, J= 4.7, 1.6 Hz, 1H), 7.52-7.49 (m, 1H), 6.96-6.94 (m, 1H),6.94-6.91 (m, 1H), 6.88 (d, J= 4.1Hz, 1H), 6.83 (d, J= 7.6 Hz, 1H),6.82-6.80 (m, 1H), 6.71 (t, J= 7.9Hz, 1H), 6.55-6.47 (m, 2H), 6.41 (td, J=9.0, 1.6 Hz, 1H); 13C NMR (125 MHz, acetone-d6) delta 180.8,154.6, 154.4, 148.7, 143.6, 139.3, 138.3, 137.0, 135.9, 135.0, 131.5, 126.5,125.1, 123.8, 122.8, 120.4, 119.4, 112.6, 112.4; MS (ESI): 473.28 (M+H)+)+; HPLC purity ? 95percent (Rt = 10.75 min). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With triethylamine; In N,N-dimethyl-formamide; at 0 - 25℃; for 2h; | A solution of 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-amine hydrochloride (0.100 g, 0.346 mmol) in DMF (1.0 mL) was cooled to 0 C, treated with triethylamine (150 L, 1.07 mmol), and <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (0.0820 g, 0.381 mmol). The mixture was warmed to 25 C, and stirred for 2 h. The mixture was partitioned between saturated aqueous NaCl (20 mL), and CH2Cl2 (20 mL). The organic layer was washed with a H2O (2 20 mL), saturated aqueous NaCl (20 mL), dried (Na2SO4), and concentrated in vacuo. The residue was dissolved in a minimal amount of CH2Cl2 and purified by flash chromatography (SiO2, 0-20percent ethyl acetate-hexanes). The purified fractions were concentrated in vacuo, the residue was suspended in a minimal amount of ethyl ether and then precipitated with the addition of hexanes to afford the title compound as a white solid (0.0939 g, 69percent). 1H NMR (600 MHz, CDCl3) 8.98 (1H, s), 8.74 (1H, d, J = 3.0 Hz), 7.96 (1H, d, J = 7.8 Hz), 7.33 (1H, q, J = 4.8 Hz), 7.12 (2H, t, J = 6.6 Hz), 7.09 (2H, d, J = 7.8 Hz), 6.99 (2H, d, J = 7.8 Hz), 6.94 (2H, d, J = 7.2 Hz), 4.84 (1H, br s), 3.73 (2H, t, J = 5.4 Hz), 3.08 (4H, s), 3.05 (2H, m), 1.76 (2H, quintet, J = 6.0 Hz); 13C NMR (150 MHz, CDCl3) 153.3, 148.2, 147.9, 136.8, 134.8, 134.4, 130.3, 126.8, 123.9, 123.2, 119.8, 47.4, 41.5, 32.2, 27.7; LCMS m/z 394.3 ([M + H+], C22H23N3O2S requires 394.2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With pyridine; at 20℃; for 2h; | To a mixture of 3-(phenylamino)-2-(pyridin-4-yl)-1 .5,6,7-tetrahydro-4H-pyrrolo[2,3- c]pyridin-4-one (14; 30 mg, 0.10 mmol) in pyridine (1 mL) was added <strong>[42899-76-3]pyridine-3-sulfonyl chloride hydrochloride</strong> (42 mg, 0.20 mmol) and stirred for 2 h at RT. Methanol was added and the mixture concentrated and purified by preparative TLC (silica, EtOH:DCM) to give the title compound (20 mg, 44percent). 1H-NMR (400 MHz, DMSO-d6), delta [ppm]= 3.97 (2H), 4.78 (2H), 6.34 (2H), 6.61 (1 H), 7.03 (2H), 7.32 ( 1 H), 7.43 (2H), 7.55 (1 H), 8.1 1 (1 H), 8.44 (2H), 8.78 (1 H), 8.87 (1 H), 12.18 (1 H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | To a solution of 5-(2-fluorophenyl)-lH-pyrrole-3-carboxylic acid ethyl ester (4 g) in tetrahydrofuran (50 mL) was added sodium hydride (60percent in oil, 0.5 g) and the mixture was added Stir for more than 30 minutes. Pyridine-3-sulfonyl chloride hydrochloride (1 g) was added and stirred for 3 more hours. After the reaction was completed, it was quenched with saturated brine, and the mixture was extracted with 50 mL of ethyl acetate. The extract was washed with saturated brine and concentrated. Crystallization with methyl tert-butyl ether and ethyl acetate (1:1) gave colorless crystals (yield 80percent, purity 96percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | The title compound was prepared by the introduction of pyridine-3-sulfonyl chloride, (0356) hydrochloride (23 mg, 0.11 mmol) on the 6-{(2-Ghloro-6 luorophenoxy)methy1}-1 H-indole (20 mg, 0,07 rrsrnol) according to General Procedure A- The crude product was purified by (0357) preparative HPLC (20-100percent CH3C /fv1eOH {1 :1} in H20 (0.01 percent TFA)} which provided after lyophilization 8 mg (21 percent) of the title compound as a colorless solid as the TFA salt; 1H N R (400 MHz, MeOD) delta = 9.06 (s, 1 H), 8.75 (d, J = 4.0 Hz, 1 H), 8,31 - 8,23 (m, 1 H), 8.18 s, 1 H), 7.72 (d, J - 3.8 Hz, 1 H), 7.58 - 7,50 (m, 2 H), 7.35 (dd, J FontWeight="Bold" FontSize="10" 1 .3, 8,1 Hz, 1 H), 7.21 (id, J ~ 1.6, 7.9 Hz, 1 H), 7.15 - 7.02 (m, 2 H), 6.79 (dd, J = 0,8, 3.8 Hz, 1 H), 5.2 (s, 2 H). MS (ESI*) mfe 416,75 [Mu?Eta General Procedure A: Preparation of N-sufonyl. To the soiuiion of N-B-indoie (1 eq.) in DCM (C: 0.5 mmol/mL) were added KOH (2 eq.) and TBAHS (0.15 eq.) at room temperature. The reaction mixture was stirred 20 min before addition of arySsuifonyi chloride (1 .5 eq.}. The reaction was stirred at the same temperature for 6-12h. The completion of the reaction was monitored by HPLC. Upon completion, l-Q was added and the reaction mixture was extracted with DCM. The combined organic layers were washed with brine and dried over NaaSO-*. (0253) Filtration and removal; of the solvent provided the crude product, which was purified by (0254) Combifiash silica gel chromatography or preparative HPLC to afford the corresponding products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12.9% | With dmap; triethylamine; In dichloromethane; at 20℃; for 48h; | To a dichloromethane (5.0 mL) solution of 2-[(4aS,8aR)-octahydroisoquinolin-2(1H)-yl]-5-(trifluoromethyl)aniline (120 mg, 0.402 mmol) synthesized by the method described in the document (PCT Int. Appl. (2009), WO2009119167 A1 20091001.), <strong>[42899-76-3]3-pyridinesulfonyl chloride hydrochloride</strong> (130 mg, 0.607 mmol, commercial product), triethylamine (0.40 mL, 2.89 mmol, commercial product), and N,N-dimethyl-4-aminopyridine (10 mg, 0.082 mmol, commercial product) were added sequentially at room temperature and thereafter this was stirred for 48 hours. Water was added to this reaction mixture to stop the reaction, followed by extraction with ethyl acetate (*3). This was washed with saturated saline and then dried over anhydrous sodium sulfate. After this was filtered, the filtrate was concentrated under reduced pressure. The resultant reaction crude product was purified by silica gel column chromatography (Kanto Chemical Co., Inc., neutral and spherical, 10 g, hexane/ethyl acetate=5/1 to 1/1) and then was purified again by preparative TLC (hexane/ethyl acetate=1/1). Thus, N-(2-((4aS,8aR)-octahydroisoquinolin-2(1H)-yl)-5-(trifluoromethyl)phenyl)-3-pyridine-sulfonamide (22.8 mg, 0.0519 mmol, 12.9%) (Compound 5) was obtained as colorless crystals. TLC Rf 0.21 (hexane/ethyl acetate=2/1); 1H NMR (CDCl3, 400 MHz) delta 0.87-1.13 (m, 3H), 1.22-1.51 (m, 5H), 1.52-1.81 (m, 4H), 2.24 (dd, 1H, J=10.8 10.8 Hz), 2.36-2.42 (m, 1H), 2.51-2.63 (m, 2H), 7.16 (d, 1H, J=8.4 Hz), 7.30 (dd, 1H, J=8.4, 1.6 Hz), 7.41 (ddd, 1H, J=8.0, 4.8, 0.8 Hz), 7.85 (d, 1H, J=1.6 Hz), 8.06-8.13 (m, 2H), 8.76 (dd, 1H, J=4.8, 1.2 Hz), 9.04 (dd, 1H, J=2.4, 0.8 Hz). |
12.9% | With dmap; triethylamine; In dichloromethane; for 48h; | <strong>[42899-76-3]3-pyridinesulfonyl chloride hydrochloride</strong> (130 mg, 0.607 mmol, a commercial product), triethylamine (0.40 mL, 2.89 mmol, a commercial product), and N,N-dimethyl-4-aminopyridine (10 mg, 0.082 mmol, a commercial product) were successively added at room temperature to a dichloromethane solution (5.0 mL) containing 2-[(4aS,8aR)-octahydroisoquinolin-2(1H)-yl]-5-(trifluoromethyl)aniline (120 mg, 0.402 mmol) synthesized using the method cited in the reference (PCT Int. Appl.(2009), WO2009119167 A1 20091001.), and then the resulting mixture was stirred for 48 hours. After water was added to this reaction mixture to stop the reaction, extraction was performed using ethyl acetate (x3), the extracted product was washed with a saturated saline solution, and then dried using anhydrous sodium sulfate. After the resulting mixture was filtered, the filtrate was concentrated under reduced pressure. The obtained reaction crude product was purified through silica gel column chromatography (KANTO CHEMICAL CO., INC., neutral, spherical, 10 g, hexane/ethyl acetate = 5/1 to 1/1) and then purified through preparative TLC again (ethyl acetate/hexane = 1/1), and thus N-(2-((4aS,8aR)-octahydroisoquinolin-2(1H)-yl)-5-(trifluoromethyl)phenyl)-3-pyridine-s ulfonamide (22.8 mg, 0.0519 mmol, 12.9%) (Compound 5) was obtained as colorless crystals. TLC Rf0.21 (hexane/ethyl acetate = 2/1); 1H NMR (CDCl3, 400 MHz) delta 0.87-1.13 (m, 3H), 1.22-1.51 (m, 5H), 1.52-1.81 (m, 4H), 2.24 (dd, 1H, J = 10.8 10.8 Hz), 2.36-2.42 (m, 1H), 2.51-2.63 (m, 2H), 7.16 (d, 1H, J = 8.4 Hz), 7.30 (dd, 1H, J = 8.4, 1.6 Hz), 7.41 (ddd, 1H, J = 8.0, 4.8, 0.8 Hz), 7.85 (d, 1H, J = 1.6 Hz), 8.06-8.13 (m, 2H), 8.76 (dd, 1H, J = 4.8, 1.2 Hz), 9.04 (dd, 1H, J = 2.4, 0.8 Hz). |
Tags: 42899-76-3 synthesis path| 42899-76-3 SDS| 42899-76-3 COA| 42899-76-3 purity| 42899-76-3 application| 42899-76-3 NMR| 42899-76-3 COA| 42899-76-3 structure
[ 489430-50-4 ]
Pyridine-4-sulfonyl chloride hydrochloride
Similarity: 0.84
[ 65001-21-0 ]
5-Bromopyridine-3-sulfonyl chloride
Similarity: 0.84
[ 889944-76-7 ]
6-Chloro-4-methylpyridine-3-sulfonyl chloride
Similarity: 0.78
[ 6684-39-5 ]
2-Chloro-5-pyridinesulfonyl chloride
Similarity: 0.67
[ 489430-50-4 ]
Pyridine-4-sulfonyl chloride hydrochloride
Similarity: 0.84
[ 65001-21-0 ]
5-Bromopyridine-3-sulfonyl chloride
Similarity: 0.84
[ 889944-76-7 ]
6-Chloro-4-methylpyridine-3-sulfonyl chloride
Similarity: 0.78
[ 6684-39-5 ]
2-Chloro-5-pyridinesulfonyl chloride
Similarity: 0.67
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :