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HazMat fee for 500 gram (Estimated)
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USD 0.00
Limited Quantity
USD 15-60
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USD 80+
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Structure of 636-73-7 * Storage: {[proInfo.prStorage]}
* 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.
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1958, vol. 77, p. 963,968, 970
2
[ 110-86-1 ]
[ 7664-93-9 ]
[ 626-64-2 ]
[ 5402-20-0 ]
[ 636-73-7 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1958, vol. 77, p. 963,968, 970
3
[ 636-73-7 ]
[ 16133-25-8 ]
Yield
Reaction Conditions
Operation in experiment
94%
for 3 h; Heating / reflux
A mixture of pyridine-3-sulfonic acid (10.3 g, 64.8 mmol), phosphorus pentachloride (20.82 g, 100 mmol) and phosphorus oxychloride (10 mL, 109 mmol) was heated to reflux for 3 h (according to J. Org. Chem. 1989, 54(2), 389.). Evaporated to dryness to give a yellow solid, dissolved in ice water and methyl-tert-butyl ether, added cautiously sat. NaHCO3-sol. until neutralized, saturated with solid NaCl, separated phases, dried organic layer over Na2SO4. Removal of the solvent in vacuum to give the title compound as an orange liquid (10.85 g, 94percent). MS (ISP) 178.1 [(M+H)+] and 180.0 [(M+2+H)+].
90%
for 8 h; Reflux
A 3-pyridine sulfonyl chloride is synthesized by using 3-pyridine sulfonic acid as a starting material in U.S. Patent Nos. CN200680040789, US2006 / 217387, Merck & apos; s US5416099A1,Method for 3-pyridine sulfonic acid in phosphorus pentachloride and phosphorus oxychloride reflux for 8 hours or more to be completed after the reaction with a greater amount of water quenching reaction,After the extraction, distillation,Distillation method to obtain high purity 3-pyridyl sulfonyl chloride,The yield of this method can reach more than 90percent.
89.6%
at 25 - 80℃; for 12 h; Inert atmosphere
Pyridine-3-sul on l chloride (A4) A3 A4 To a mixture of A3 (9.00 g, 56.6 mmol) in SOCl2 (108.00 mL) was added DMF (5.00 mL) in one portion at 25°C under N2. The mixture heated to 80 °C and stirred for 12 hours, after which LCMS analysis indicated the reaction was complete. The reaction mixture was concentrated under reduced pressure to give A4 (9.00 g, yield: 89.6percent), which was used in the next step without further purification. 1H NMR (400 MHz, CDC13) δ: 8.98(s, 1H), 8.91 (d, / = 5.6 Hz, 1H), 8.72 (d, / = 8.0 Hz, 1H), 8.07-8.10 (m, 1H).
88%
at 20 - 110℃; for 17 h; Heating / reflux
Pyridine-3-sulfonic acid (125 g, 0.78 m) was placed in a 1L, 3-necked flask equipped with mechanical stirrer, reflux condenser, thermometer and nitrogen inlet. Next, the phosphorus pentachloride (250 g, 1.19 m, 1.5 eq) was added, followed immediately by the phosphorus oxychloride (330 ml, 3.8 m, 4.5 eq). The contents of flask were initially stirred at ambient temperature for 30 min, then brought slowly to gentle reflux (internal temp. approx. 110° C.) over the next hour, kept at this temperature for approx. 3.5 hr then allowed over the next 12 hr to cool back to ambient temperature. Gas evolution was observed during this time. The volatiles were stripped under reduced pressure (at 12 mmHg/40° C.) and yellow semi-solid residue was diluted with DCM (1 L). The slurry was poured slowly into the stirred, ice-cold sat. aq. bicarbonate, maintaining pH=7. Gas evolution was observed. The organic layer was separated and aqueous layer was back-extracted with DCM. The combined extracts were washed with cold sat. aq. bicarbonate, brine and dried with magnesium sulfate. The solids were filtered off and filtrate evaporated, leaving pyridine-3-sulfonyl chloride as a pale yellow, oily liquid, 123 g (93percent pure; 88percent theory).
88%
Stage #1: at 20 - 110℃; for 17 h; Heating / reflux Stage #2: With sodium hydrogencarbonate In dichloromethane; water
Pyridine-3 -sulfonic acid (125 g, 0.78 m) was placed in a IL, 3 -necked flask equipped with mechanical stirrer, reflux condenser, thermometer and nitrogen inlet. Next, the phosphorus pentachloride (250 g, 1.19 m, 1.5 eq) was added, followed immediately by the phosphorus oxychloride (330ml, 3.8 m, 4.5 eq) . The contents of flask were initially stirred at ambient temperature for 30 min, then brought slowly to gentle reflux (internal temp, approx. HO0C) over the next hour, kept at this temperature for approx. 3.5 hr then allowed over the next 12 hr to cool back to ambient temperature. Gas evolution was observed during this time. The volatiles were stripped under reduced pressure (at 12 mmHg/40°C) and yellow semi-solid EPO <DP n="77"/>residue was diluted with DCM (IL) . The slurry was poured slowly into the stirred, ice-cold sat. aq. bicarbonate, maintaining pH=7. Gas evolution was observed. The organic layer was separated and aqueous layer was back-extracted with DCM. The combined extracts were washed with cold sat. aq. bicarbonate, brine and dried with magnesium sulfate. The solids were filtered off and filtrate evaporated, leaving pyridine-3- sulfonyl chloride as a pale yellow, oily liquid, 123 g (93percent pure; 88percent theory). 1H-NMR, CDCl3, (δ) : 9.26 (d, IH), 8.98 (dd, IH), 8.34 (m, IH), 7.62 (m, IH) . 13C-NMR, CDCl3, (δ) : 155.3, 147.4, 140.9, 134.6, 124.2. MS (m/z) : 178.0 [M+1] .L-penicillamine (150 g, 1.0 m) was dissolved with stirring in DI water (1500 ml) , cooled in ice-bath to +8°C and treated with formalin (150 ml, 37percent aq.) . The reaction mixture was stirred at +8°C for 2 hr, then cooling bath was removed and stirring continued for 12 hr. The clear solution was concentrated under reduced pressure (14 mmHg/50°) leaving white residue. The solids were re-suspended, then dissolved in hot MeOH (2500 ml) and left standing at ambient temperature for 12 hr. The white, fluffy precipitate was filtered off and rinsed with cold methanol. The filtrate was concentrated and set to crystallize again. The collected precipitate was combined with the first crop and dried in vacuum oven for 24 hr at 55°C at 45 mmHg. The yield of (R) -5 , 5-dimethylthiazolidine-4-carboxylic acid was 138 g (>99percent pure; 86percent theory) . 1H-NMR, DMSO-d6, (δ) : 4.25 (d, IH), 4.05 (d, IH), 3.33 (s, IH), 1.57 (s, 3H), 1.19 (s, 3H). 13C-NMR, DMSO-d6, (6): 170.8, 74.4, 57.6, 51.8, 28.9, 27.9. MS (m/z): 162.3 [M+l] . In a 4L reactor equipped with mechanical stirrer and thermometer, a buffer solution was prepared from potassium monobasic phosphate (43 g, 0.31 m) and potassium dibasic phosphate (188.7 g, 1.08 m) in DI water (2L). The (R) -5,5- EPO <DP n="78"/>dimethylthiazolidine-4-carboxylic acid (107 g, 0.675 m) was added and stirred until complete dissolution. The solution was cooled in an ice-bath to +80C. A separately prepared solution of pyridine-3-sulfonyl chloride (124 g, 0.695 m) in DCM (125 ml) was added dropwise to the reactor with vigorous stirring over the 1 hr. The pH of reaction mixture was monitored and after 4 hr, found to be pH=5 and adjusted to pH=6 by addition of solid bicarbonate. The mixture was allowed to warm up to ambient temperature over 18 hr. The pH was adjusted to 2 with dil . aq. sulfuric acid, stirred for 1 hr and precipitated yellow solids were filtered off, rinsed with water to neutral. The solid cake was transferred into 2L Erlenmayer flask, suspended in DCM (500 ml) with occasional swirling for 5 min and filtered off again. The filter cake was washed with DCM and air-dried. The yield of the title compound, (R) -5, 5 -dimethyl - 3- (pyridin-3-ylsulfonyl) thiazolidine-4-carboxylic acid was 148.9 g (98percent pure; 73percent theory). 1H-NMR, DMSO-d6, (δ) : 9.05 (d, IH), 8.89 (m, IH), 8.32 (m, IH), 7.69 (m, IH), 4.68 (q, 2H), 4.14 (s, IH), 1.35 (s, 3H), 1.29 (s, 3H). 13C-NMR, DMSO-d6, (δ) : 170.0, 154.3, 147.9, 135.8, 134.1, 124.8, 72.6, 54.3, 50.2, 29.4, 25.0. MS (m/z) : 303.2 [M+l] .
87.9%
With phosphorus pentachloride In chlorobenzene at 105℃; for 3 h;
Example 1 (chlorobenzene solvent) 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde (0141) Pyridine-3-sulfonic acid (10.7 g, 68.5 mmol) and phosphorus pentachloride (15.7 g, 75.4 mmol) were suspended in chlorobenzene (15 mL) at room temperature. After heating and stirring at an inside temperature of 105±5°C for about 3 hr, the mixture was cooled to room temperature. Toluene (50 mL) and water (30 mL) were added into another kolben, and the mixture was cooled to an inside temperature of 5±5°C. The reaction solution was added dropwise at not more than an inside temperature of 15°C, and the dropping funnel was washed well with a mixed solution of toluene and water (1:1, 20 mL). After cooling to an inside temperature of 5±5°C, 50percent aqueous potassium carbonate solution (39 mL) was added dropwise at not more than an inside temperature of 20°C, and the mixture was adjusted to pH 7.5±0.5. After partitioning at room temperature, the organic layer was washed with 5percent brine (40 mL), and concentrated to about 20 mL under reduced pressure. Toluene (40 mL) was added and the mixture was concentrated again to about 20 mL. An operation of adding acetonitrile (40 mL) and concentrating the mixture to about 20 mL was repeated three times to give an acetonitrile solution of pyridine-3-sulfonylchloride (quantified yield 10.7 g, 87.9percent, total amount 20.3 g, 52.7 w/wpercent acetonitrile solution). (0142) To the acetonitrile solution (total amount) of pyridine-3-sulfonylchloride obtained above were added acetonitrile (45 mL), 5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde (10.0 g, 52.9 mmol), N,N-dimethylpyridin-4-amine (0.646 g, 5.29 mmol) and triethylamine (10.4 mL, 74.1 mmol), and the mixture was heated to an inside temperature of 45±5°C. After stirring at an inside temperature of 45±5°C for 1.5 hr, the mixture was cooled to room temperature, and water (30 mL) was added dropwise. The mixture was adjusted to pH 4 - 5 with 0.5M hydrochloric acid (about 20 mL). The seed crystal of the title compound was added and, after confirmation of crystal precipitation, water (60 mL) was added dropwise. After stirring at room temperature for 30 min and at 5±5°C for 1 hr, the precipitated crystals were collected by filtration. The crystals were washed twice with a mixed solution of acetonitrile and water (1:2, 30 mL) cooled to 5±5°C in advance, and dried at an outer temperature of 50°C under reduced pressure to give the title compound (15.5 g, isolation yield 88.7percent). 1H NMR (500 MHz, CDCl3) δ 6.68 (d, J = 1.6 Hz, 1H), 7.02 (dd, J = 8.2, 8.2 Hz, 1H), 7.14-7.19 (m, 2H), 7.38 (dd, J = 8.2, 4.9 Hz, 1H), 7.44-7.48 (m, 1H), 7.72 (ddd, J = 8.2, 2.5, 1.6 Hz, 1H), 8.17 (d, J = 1.9 Hz, 1H), 8.59 (d, J = 1.9 Hz, 1H), 8.82 (dd, J = 4.7, 1.6 Hz, 1H), 9.90 (s, 1H).
85%
With phosphorus pentachloride In trichlorophosphate at 120℃;
Reference Example 18: Pyridine-3-sulfonyI chloride. A mixture of pyridine-3-sulfonic acid (3 g, 18.8 mmol), phosphorus pentachloride (6.04 g, 29.0 mmol) and phosphorus oxychloride (15 mL) was heated at12O0C overnight. Excess phosphorus oxychloride was evaporated under reduced pressure, the residue quenched with ice and partitioned between water and diethyl ether.The pH of the aqueous phase was adjusted by addition of-solid sodium bicarbonate to pH 7-8, then the organic layer was separated and washed successively with sat. sodium bicarbonate solution, water and brine. The organice phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a residue which was dried under high vacuum to afford pyridine-3-sulfonyl chloride (2.83 g, 85percent) as a solid.
83.9%
With phosphorus pentachloride In chlorobenzene at 119 - 122℃;
In 100mL four-necked flask, pyridine-3-sulfonic acid 15.9g (0.100 mol) and put the monochlorobenzene 23.9g, was heated with stirring to 120 ° C. While maintaining the internal temperature at 119~122 ° C, it was placed in every 5 minutes for 20 split the phosphorus pentachloride 20.4g (0.098 mol). After the addition completion of the phosphorus pentachloride and stirred for an additional 1 hour. When the reaction liquid was subjected to gas chromatography (GC) analysis of the concentration of the pyridine-3-sulfonyl chloride was 29.5 wtpercent. Moreover, it was calculated from the amount of the reaction liquid (54.3 g), pyridine-3-sulfonyl chloride The yield in the reaction solution is 90.2percent by-produced 5-chloropyridine-3-sulfonyl chloride area by GC analysis ratio (5-chloropyridine-3-sulfonyl chloride / pyridine-3-sulfonyl chloride) was 0.02percent.The reaction solution was concentrated under reduced pressure to 3.6kPa at 90 ° C, followed by distilling off the monochlorobenzene and by-product phosphorus oxychloride. Then, 94 ° C, then vacuum distillation under the conditions of 0.4 kPa, to give a pyridine-3-sulfonyl chloride 14.9 g. Pyridine-3-sulfonyl chloride yield was 83.9percent. The area ratio by GC analysis and pyridine-3-sulfonyl chloride 99.99percent 5-chloro-3-sulfonyl chloride was 0.01percent.
75%
With phosphorus pentachloride In trichlorophosphate for 4 h; Reflux
Step 1: Preparation of pyridin-3-sulfonyl chloride Pyridin-3-sulfonic acid (5.0 g, 31.4 mmol) was added with phosphorous pen- tachloride (9.8 g, 47.1 mmol) and phosphorous oxychloride (10 ml), stirred underreflux for 4 hours, and then the mixture was concentrated to remove phosphorous oxy chloride. The reaction mixture was added with ice water and diethyl ether, stirred, and then extracted into the organic layer. The resulting separated organic layer was washedwith a saturated sodium bicarbonate solution, and the organic layer was dried on anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 4.1 g of a title compound (yield: 75percent).[563] 1H NMR (500 MHz, CDCb): 8.91 (s, lH), 8.84 (d, lH), 8.43 (dd, lH), 7.57 (t, lH) [564]
66%
at 130℃; for 20 h;
3-Pyridine sulfonic acid (4.0 g, 25.1 mmol, 1 eq) and PCl5 (5.75 g, 27.70 mmol, 1.1 eq) were heated at 130 °C for 20 h. After cooling, ice was added and the mixture was extracted with EtOAc (*3). The combined organic layers were washed with saturated aqueous NaHCO3 (*1), brine (*1) and dried over sodium sulphate. After filtration and evaporation of the solvent a yellow oil is obtained. (2.94 g, 66percent). 1H NMR (300 MHz, CDCl3) δ 9.17 (d, J = 2.4 Hz, 1-H) 8.91 (dd, J = 4.9/1.5 Hz, 1-H), 8.26 (ddd, J = 8.3/2.5/1.8 Hz, 1-H), 7.57 (ddd, J = 8.3/4.9/0.6 Hz, 1-H); 13C NMR (75 MHz, CDCl3) δ 155.6, 147.5, 141.0, 139.7, 124.4; IR (KBr) 3045, 1625, 1522, 1375, 1247, 1173 cm-1.
64%
at 135℃; for 2.5 h;
[0310] A mixture of pyridine-3 -sulfonic acid (5.0 g, 31.4 mmol, 1.0 eq) and PC15 (14.2 g, 69.1 mmol, 2.2 eq) was refluxed at 135 °C for 2.5 hrs. The resulting mixture was cooled to r.t., triturated with chloroform, filtered and dried to give 3.6 g of Compound Int-18 (64percent yield) as a white solid.
92%
With phosphorus pentachloride In toluene
STR121 3-Pyridylsulfonyl chloride (23-10) 3-Pyridylsulfonic acid (30 g, 0.188 mole) was added to PCl5 (46.8 g, 0.225 mole), suspended in 150 mL toluene and heated to reflux overnight. The suspension was cooled and concentrated to yield a yellow oil, which was diluted with benzene, filtered through a pad of celite and concentrated to give 30.7 g (92percent) of 23-10 as a yellow oil, which was used in the next step without purification. 1 H NMR (300 MHz, CDCl3) δ 9.27 (1H, s), 8.98 (1H, d, 8.35 (1H, d), 7.62 (1H, dd).
0.70 g
With phosphorus pentachloride In toluene for 16 h; Reflux
Pyridine-3-sulfonyl chloride Phosphorus pentachloride (1.57 g, 7.5 mmol) was added to a stirred solution of pyridine-3-sulfonic acid (1.00 g, 6.3 mmol) in toluene (5 mL). The mixture was heated at reflux for 16 hours and then cooled to room temperature. The mixture was filtered through celite, and the celite was washed with benzene (2*10 mL). The combined filtrates were concentrated under reduced pressure to give crude pyridine-3-sulfonyl chloride (0.70 g, 100percent), which was used directly in the next step without further purification.
Reference：
[1] Journal of the American Chemical Society, 1992, vol. 114, # 12, p. 4889 - 4898
[2] Patent: US2006/217387, 2006, A1, . Location in patent: Page/Page column 25
[3] Journal of Medicinal Chemistry, 1999, vol. 42, # 13, p. 2409 - 2421
[4] Patent: CN106432067, 2017, A, . Location in patent: Paragraph 0090
[5] Patent: WO2016/90317, 2016, A1, . Location in patent: Page/Page column 73
[6] Patent: US2006/13799, 2006, A1, . Location in patent: Page/Page column 55
[7] Patent: WO2006/127584, 2006, A1, . Location in patent: Page/Page column 60; 75-77
[8] Patent: EP2963019, 2016, A1, . Location in patent: Paragraph 01410; 0141; 0145
[9] Patent: WO2008/62182, 2008, A1, . Location in patent: Page/Page column 114
[10] Patent: JP5826964, 2015, B1, . Location in patent: Paragraph 0046; 0047
[11] Patent: WO2015/50412, 2015, A1, . Location in patent: Paragraph 558; 559; 561; 562; 563
[12] Journal of Organic Chemistry, 1989, vol. 54, # 2, p. 389 - 393
[13] European Journal of Medicinal Chemistry, 2012, vol. 55, p. 58 - 66,9
[14] Patent: WO2018/85348, 2018, A1, . Location in patent: Paragraph 0310
[15] Journal of the American Pharmaceutical Association (1912-1977), 1948, vol. 37, p. 99
[16] Monatshefte fuer Chemie, 1939, vol. 72, p. 77,88
[17] J. Franklin Inst., 1943, vol. 236, p. 316,318
[18] Synthesis, 1983, # 10, p. 822 - 824
[19] Journal of Organic Chemistry, 1991, vol. 56, # 11, p. 3470 - 3472
[20] Journal of Heterocyclic Chemistry, 1992, vol. 29, # 1, p. 61 - 64
[21] Bioorganic and medicinal chemistry letters, 2002, vol. 12, # 16, p. 2097 - 2100
[22] Patent: US2003/187001, 2003, A1,
[23] Patent: US5416099, 1995, A,
[24] Patent: US5646000, 1997, A,
[25] Patent: US5686486, 1997, A,
[26] Patent: US4550114, 1985, A,
[27] Chemistry - A European Journal, 2010, vol. 16, # 41, p. 12474 - 12480
[28] Organic Letters, 2011, vol. 13, # 14, p. 3588 - 3591
[29] Patent: US2012/214803, 2012, A1, . Location in patent: Page/Page column 125
[30] Crystal Growth and Design, 2012, vol. 12, # 9, p. 4567 - 4573
[31] Patent: US2013/150407, 2013, A1, . Location in patent: Paragraph 0194; 0195
[32] European Journal of Medicinal Chemistry, 2017, vol. 129, p. 124 - 134
[33] Journal of Medicinal Chemistry, 2017, vol. 60, # 9, p. 3795 - 3803
4
[ 636-73-7 ]
[ 16133-25-8 ]
Yield
Reaction Conditions
Operation in experiment
92%
With phosphorus pentachloride In toluene
5-[2-(Piperidin-4-yl)ethyl]thieno-[2,3-b]thiophene-2-N-[3-2(S)-(2-ethoxyethanesulfonylamino)propionic acid]carboxamide (2-14) 3-4 was treated with 2-13 and this intermediate was deprotected as described for 1-10 to give pure 2-14. 1 H NMR (300 MHz, D2 O) δ1.03 (3H, t), 1.20-1.53 (5H, m), 1.75 (2H, bd), 2.60 (2H, bs), 2.73 (2H, bt), 3.34 (6H, m), 3.50 (1H, m), 3.75 (4H, m), 4.27 (1H, m), 6.80 (1H, s), 7.62 (1H, s). STR38 3-Pyridylsulfonyl chloride (2-15) 3-pyridylsulfonic acid (30 g, 0.188 mole) was added to PCl5 (46.8 g, 0.225 mole), suspended in 150 mL toluene and heated to reflux overnight. The suspension was cooled and concentrated to yield a yellow oil, which was diluted with benzene, filtered through a pad of celite and concentrated to give 30.7 g (92percent) of 2-15 as a yellow oil, which was used in the next step without purification. 1 H NMR (300 MHz, CDCl3) δ9.27 (1H, s), 8.98 (1H, d, 8.35 (1H, d), 7.62 (1H, dd).
Reference：
[1] Patent: US5397791, 1995, A,
5
[ 110-91-8 ]
[ 636-73-7 ]
[ 16133-25-8 ]
Reference：
[1] Patent: US2003/187254, 2003, A1,
6
[ 636-73-7 ]
[ 10026-13-8 ]
[ 16133-25-8 ]
Reference：
[1] Patent: US6479519, 2002, B1,
7
[ 1851-22-5 ]
[ 636-73-7 ]
Reference：
[1] Patent: US5082944, 1992, A,
[2] Patent: US5082944, 1992, A,
8
[ 110-86-1 ]
[ 636-73-7 ]
Reference：
[1] Chemische Berichte, 1882, vol. 15, p. 63
[2] Monatshefte fuer Chemie, 1914, vol. 35, p. 769
[3] Patent: US2409806, 1941, ,
[4] Journal of the American Chemical Society, 1933, vol. 55, p. 2854
[5] Recueil des Travaux Chimiques des Pays-Bas, 1934, vol. 53, p. 1031,1033
[6] Roczniki Chemii, 1952, vol. 26, p. 158,161[7] Chem.Abstr., 1956, p. 338
[8] Patent: US2406972, 1943, ,
[9] Journal of the American Chemical Society, 1943, vol. 65, p. 2233,2235
[10] Monatshefte fuer Chemie, 1939, vol. 72, p. 77,88
[11] J. Franklin Inst., 1943, vol. 236, p. 316,317
[12] Recueil des Travaux Chimiques des Pays-Bas, 1958, vol. 77, p. 963,968, 970
[13] Chemische Berichte, 1942, vol. 75, p. 1108,1117
[14] Zhurnal Obshchei Khimii, 1955, vol. 25, p. 1162,1169; engl. Ausg. S. 1115, 1118
[15] Journal of the American Pharmaceutical Association (1912-1977), 1948, vol. 37, p. 99
[16] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 17, p. 2443
[17] Chemische Berichte, 1884, vol. 17, p. 764
[18] Monatshefte fuer Chemie, 1895, vol. 16, p. 753
[19] Chemische Berichte, 1882, vol. 15, p. 63
[20] Monatshefte fuer Chemie, 1914, vol. 35, p. 766
[21] Roczniki Chemii, 1952, vol. 26, p. 158,161[22] Chem.Abstr., 1956, p. 338
[23] Patent: US2406972, 1943, ,
9
[ 109-00-2 ]
[ 636-73-7 ]
Reference：
[1] Chemische Berichte, 1884, vol. 17, p. 764
10
[ 110-86-1 ]
[ 7664-93-9 ]
[ 636-73-7 ]
Reference：
[1] Chemische Berichte, 1931, vol. 64, p. 1584 Anm.
[2] Chemische Berichte, 1927, vol. 60, p. 1175 Anm. 3
[3] Chemische Berichte, 1926, vol. 59, p. 1166,1977
[4] Chemische Berichte, 1884, vol. 17, p. 764
[5] Monatshefte fuer Chemie, 1895, vol. 16, p. 753
[6] Chemische Berichte, 1882, vol. 15, p. 63
11
[ 110-86-1 ]
[ 7664-93-9 ]
[ 7446-11-9 ]
[ 636-73-7 ]
Reference：
[1] Chemische Berichte, 1931, vol. 64, p. 1584 Anm.
[2] Chemische Berichte, 1927, vol. 60, p. 1175 Anm. 3
[3] Chemische Berichte, 1926, vol. 59, p. 1166,1977
[4] Chemische Berichte, 1884, vol. 17, p. 764
[5] Monatshefte fuer Chemie, 1895, vol. 16, p. 753
[6] Chemische Berichte, 1882, vol. 15, p. 63
12
[ 110-86-1 ]
[ 7664-93-9 ]
[ 636-73-7 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1958, vol. 77, p. 963,968, 970
13
[ 110-86-1 ]
[ 7664-93-9 ]
[ 626-64-2 ]
[ 5402-20-0 ]
[ 636-73-7 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1958, vol. 77, p. 963,968, 970
14
[ 29452-57-1 ]
[ 636-73-7 ]
Reference：
[1] Chemische Berichte, 1924, vol. 57, p. 2081
15
[ 636-73-7 ]
[ 60-29-7 ]
[ 75-09-2 ]
[ 2922-45-4 ]
Yield
Reaction Conditions
Operation in experiment
68.9%
With pyridine; dmap In water
EXAMPLE 4 STR109 Combine 100 mg (0.626 mmol) of 3-pyridinesulfonic acid and 3 mL of anhydrous pyridine at 0° C. and add 100 mg (0.406 mmol) pf 4-nitrobenzenesulfonyl chloride. Add 5 mg of DMAP and stir the mixture at 0° C. for 7 hours. Add 80 mg (0.258 mmol) of the Z-amine (P-3A) from Preparation 3 and stir the mixture for 1 hour at 0° C., then overnight at 20° C. Add 50 mL of CH2 Cl2 and 20 mL of water, separate the layers, and wash the organic phase with water. Dry over MgSO4, filter and concentrate in vacuo to a residue. Chromatograph the residue (silica gel, 5percent MeOH/EtOAc+1percent concentrated NH4 OH (aqueous)), crystallize from 10 mL of Et2 O and dry the resulting solid at 60° C. in vacuo to give 180 mg (68.9percent yield) of the Z-3-pyridylsulfonamide product (E-4).
Reference：
[1] Patent: US5684013, 1997, A,
16
[ 636-73-7 ]
[ 2922-45-4 ]
Reference：
[1] Journal of the American Chemical Society, 1992, vol. 114, # 12, p. 4889 - 4898
[2] Journal of Organic Chemistry, 1991, vol. 56, # 11, p. 3470 - 3472
[3] Monatshefte fuer Chemie, 1939, vol. 72, p. 77,88
[4] European Journal of Medicinal Chemistry, 2012, vol. 55, p. 58 - 66,9
17
[ 636-73-7 ]
[ 84539-34-4 ]
Reference：
[1] Chemische Berichte, 1883, vol. 16, p. 1183
18
[ 636-73-7 ]
[ 7732-18-5 ]
[ 7726-95-6 ]
[ 84539-34-4 ]
Reference：
[1] Recueil des Travaux Chimiques des Pays-Bas, 1932, vol. 51, p. 940,949
[2] Justus Liebigs Annalen der Chemie, 1932, vol. 494, p. 301
[3] Chemische Berichte, 1883, vol. 16, p. 1183
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).
Reference：
[1] Advanced Synthesis and Catalysis, 2004, vol. 346, # 8, p. 925 - 928
[2] Patent: WO2008/3703, 2008, A1, . Location in patent: Page/Page column 82
[3] Patent: US2007/60623, 2007, A1, . Location in patent: Page/Page column 24
[4] Patent: WO2006/36024, 2006, A1, . Location in patent: Page/Page column 160
[5] Patent: EP2336107, 2015, B1, . Location in patent: Paragraph 0306
[6] Phosphorus and Sulfur and the Related Elements, 1980, vol. 8, p. 189 - 196
[7] Journal of Medicinal Chemistry, 1989, vol. 32, # 11, p. 2436 - 2442
[8] Patent: US2003/69299, 2003, A1,
[9] Patent: US4315014, 1982, A,
[10] Patent: EP1803709, 2007, A1,
[11] Patent: WO2006/33446, 2006, A1, . Location in patent: Page/Page column 68-69
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)
4-{5-[2-methoxycarbonyl-2-(pyridine-3-sulfonylamino)-ethylcarbamoyl]-thieno[2,3-<i>b</i>]thiophen-2-ylmethyl}-piperidine-1-carboxylic acid <i>tert</i>-butyl ester[ No CAS ]
methyl 2-(S)-<N-(3-pyridylsulfonyl)amino>-3-<<2-carbonyl-5-<2-<N-<(tert-butyloxy)carbonyl>piperidin-4-yl>ethyl>thieno<2,3-b>thiopheneyl>amino>propionate[ No CAS ]
4-(2-{5-[2-methoxycarbonyl-2-(pyridine-3-sulfonylamino)-ethylcarbamoyl]-thieno[3,2-<i>b</i>]thiophen-2-yl}-ethyl)-piperidine-1-carboxylic acid <i>tert</i>-butyl ester[ No CAS ]
4-(3-{5-[2-methoxycarbonyl-2-(pyridine-3-sulfonylamino)-ethylcarbamoyl]-thieno[2,3-<i>b</i>]thiophen-2-yl}-propyl)-piperidine-1-carboxylic acid <i>tert</i>-butyl ester[ No CAS ]
General procedure: To a solution of CCA(0.1548 g, 0.6 mmol) in tetrahydrofuran (3-5 mL), PPh3 (0.5246 g, 2 mmol)was added at 0-5C with stirring. A white suspension was formed to which p-toluenesulfonic acid (0.1720 g, 1 mmol) was added and stirring continued for 15 min. NaN3 (0.065 g, 1 mmol) was added and the temperature was raised up to room temperature. Stirring was continued for 1 min at room temperature. After completion of the reaction (TLC), the reaction mixture was concentrated, washed with EtOAc (4-6 mL), and cold distilled water (5 mL). The organic layer was dried with anhydrous Na2SO4, passed through a short silica-gel column using n-hexane/ethylacetate (10/1) as eluent. p-Toluenesulfonyl azide was obtained with 98% yield after removing the solvent under reduced pressure.
With sulfuric acid; mercury(II) sulfate; In pyridine; at 210℃; for 10h;
To prepare 3-hydroxypyridine 2 as a raw material, add fuming sulfuric acid to a dry reaction pot, add pyridine dropwise while stirring, add mercury sulfate, heat to 210 C, hold for 10 hours, cool to 18 C, add to ethanol, and continue Cool to below 5 C, precipitate crystals, and filter to obtain pyridine-3-sulfonic acid, melting point 345 C, yield 62%. Sodium hydroxide and pyridine-3-sulfonic acid are added to the reaction pot, melted at 160 C, and heated up Incubate at 210 C for 3h, cool to 100 C, add water to dissolve, adjust the pH to 5.2 with 30% hydrochloric acid, concentrate under reduced pressure, remove sodium chloride by filtration, adjust the filtrate to pH 7.4 with saturated sodium carbonate, cool and filter, and dry. Crude 3-hydroxypyridine was obtained with a yield of 64%. Refining with toluene yielded a refined product with a melting point of 120 C, a content of 98%, and a refined yield of 80%.
With phosphorus pentachloride; triethylamine; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; toluene;
EXAMPLE 147 Anthracen-9-yl-[3-(morpholine-4-sulfonyl)-[1,4']bipiperidinyl-1'-yl]-methanone Pyridine-3-sulfonyl chloride was prepared from phosphorus pentachloride (17.82 g, 0.112 mol) and <strong>[636-73-7]pyridine-3-sulfonic acid</strong> (12.36 g, 77.7 mmol) according to the procedure described by P. Breant et al. Synthesis, 1983, 822. Anhydrous toluene (20 mL) was added to the product and this solution added slowly to a mixture of toluene (100 mL), triethylamine (4 eq, 43 mL) and morpholine (1.5 eq, 10.3 mL) with cooling in ice water. A thick precipitate was formed. The mixture was stirred for 16 hr and then shaken with a saturated K2CO3 solution, dried over anhydrous sodium sulfate and evaporated to give a yellowish brown solid.
With hydrogenchloride; trichlorophosphate; In chloroform;
Reference Example 14 Pyridine-3-sulphonyl chloride A mixture of <strong>[636-73-7]pyridine-3-sulphonic acid</strong> (5.0 g), phosphorous pentachloride (8.0 g), phosphorous oxychloride (30 ml) and chloroform (30 ml) was stirred at 120 C. for 18 hours. The reaction mixture was cooled to room temperature then diluted with chloroform (30 ml) and then filtered. Hydrogen chloride gas was bubbled through the filtrate for 15 minutes and the resultant precipitate collected. This material was dried in vacuo to give the title compound as a white solid.
3-(1-BOC-2-(S)-pyrrolidinylmethylthioxy)pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran;
106a. 3-(1-BOC-2-(S)-pyrrolidinylmethylthioxy)pyridine To a solution of triphenylphosphine (1.8 mmol, 0.472 g) in THF (8 mL) was added DEAD (1.8 mmol, 0.283 mL) and the mixture was stirred at) C. for 20 minutes. To this mixture was added 166.5 mg (1.5 mmol) sample of 3-thiopyridine (prepared from <strong>[636-73-7]3-pyridinesulfonic acid</strong> according to the procedure of A. Albert and G. B. Barlin, J. Chem. Soc., 1959, 2384) and 361.8 mg (1.8 mmol) of (S)-1-BOC-2-pyrrolidinemethanol (from Example 15a above). The reaction mixture was warmed to room temperature and stirred for 16 hours. The mixture was concentrated in vacuo. The residue was purified on silica gel to five 440 mg of the title compound. MS (DCI/NH3) m/e: 295 (M+H)+. 1 H NMR (CDCl3, 300 MHz) delta: 8.65-8.58 (m, 1H), 8.46-8.36 (m, 1H), 7.88-7.69 (m, 1H), 4.06-3.88 (m, 1H), 3.65-32.8 (m, 4H), 2.18-1.74 (m, 4H), 1.44 (s, 9H).
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).
5-[2-(Piperidin-4-yl)ethyl]thieno-[2,3-b]thiophene-2-N-[3-2(S)-(2-ethoxyethanesulfonylamino)propionic acid]carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
30.7 g (92%)
With phosphorus pentachloride; In toluene;
5-[2-(Piperidin-4-yl)ethyl]thieno-[2,3-b]thiophene-2-N-[3-2(S)-(2-ethoxyethanesulfonylamino)propionic acid]carboxamide (2-14) 3-4 was treated with 2-13 and this intermediate was deprotected as described for 1-10 to give pure 2-14. 1 H NMR (300 MHz, D2 O) delta1.03 (3H, t), 1.20-1.53 (5H, m), 1.75 (2H, bd), 2.60 (2H, bs), 2.73 (2H, bt), 3.34 (6H, m), 3.50 (1H, m), 3.75 (4H, m), 4.27 (1H, m), 6.80 (1H, s), 7.62 (1H, s). STR38 3-Pyridylsulfonyl chloride (2-15) 3-pyridylsulfonic acid (30 g, 0.188 mole) was added to PCl5 (46.8 g, 0.225 mole), suspended in 150 mL toluene and heated to reflux overnight. The suspension was cooled and concentrated to yield a yellow oil, which was diluted with benzene, filtered through a pad of celite and concentrated to give 30.7 g (92%) of 2-15 as a yellow oil, which was used in the next step without purification. 1 H NMR (300 MHz, CDCl3) delta9.27 (1H, s), 8.98 (1H, d, 8.35 (1H, d), 7.62 (1H, dd).
EXAMPLE 4 STR109 Combine 100 mg (0.626 mmol) of <strong>[636-73-7]3-pyridinesulfonic acid</strong> and 3 mL of anhydrous pyridine at 0 C. and add 100 mg (0.406 mmol) pf 4-nitrobenzenesulfonyl chloride. Add 5 mg of DMAP and stir the mixture at 0 C. for 7 hours. Add 80 mg (0.258 mmol) of the Z-amine (P-3A) from Preparation 3 and stir the mixture for 1 hour at 0 C., then overnight at 20 C. Add 50 mL of CH2 Cl2 and 20 mL of water, separate the layers, and wash the organic phase with water. Dry over MgSO4, filter and concentrate in vacuo to a residue. Chromatograph the residue (silica gel, 5% MeOH/EtOAc+1% concentrated NH4 OH (aqueous)), crystallize from 10 mL of Et2 O and dry the resulting solid at 60 C. in vacuo to give 180 mg (68.9% yield) of the Z-3-pyridylsulfonamide product (E-4).
5-bromo-3-[N-[2-[[2-(1,2,3,4-tetrahydroisoquinolyl)carbonyloxy]ethyl]carbamoyl]ethyl-N-phenyl]carbamoylpyridine[ No CAS ]
3-[N-[2-[[2-(1,2,3,4-tetrahydroisoquinolyl)carbonyloxy]ethyl]carbamoyl]ethyl-N-phenyl]aminosulfonyl pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium hydroxide; phosphorus pentachloride; triethylamine; In chloroform; benzene;
(i) Synthesis of 3-[N-[2-[[2-(1,2,3,4-tetrahydroisoquinolyl)carbonyloxy]ethyl]carbamoyl]ethyl-N-phenyl]aminosulfonyl pyridine (328) At 180 C. were heated <strong>[636-73-7]3-pyridine sulfonic acid</strong>[7.96 g(50.0 mmol.)]and phosphorus pentachloride[20.8 g(100 mmol.)]for two hours. The reaction mixture was cooled, there was added benzene, and then insolubles were filtered off. The filtrate was concentrated under reduced pressure to obtain the sulfonyl chloride compound(226)(10.0 g). To a solution of the compound(225) synthesised in Production Example 87-v)[300 mg(0.82 mmol.)]and triethylamine[0.35 ml (2.80 mmol.)]in chloroform(5 ml) was added the sulfonyl chloride compound(226)[300 mg(1.40 mmol.)], and the mixture was stirred for 30 minutes. The reaction mixture was washed with a 1N aqueous solution of sodium hydroxide cooled with ice, then washed with water, then dried, followed by distilling off the solvent under reduced pressure. The residue was subjected to a silica gel column chromatography, eluding with ethyl acetate, to obtain the compound(328)[240 mg(57.8%)]as colorless powder. IR(Neat)cm-1: 3320(br), 3060, 1700, 1670, 1350, 1170. NMR(90MHz;CDCl3) delta: 2.43(2H,t,J=7Hz), 2.83(2H,t,J=6Hz), 3.46(2H,q,J=6Hz), 3.67(2H,t,J=6Hz), 3.87(2H,t,J=7Hz), 4.20 (2H,t,J=6Hz), 4.60(2H,s), 6.30(1H,br t,J=6Hz), 6.73 to 7.67 (l1H,m), 7.84(1H,d,J=8Hz), 8.74(1H,m).
With sodium hydroxide; sodium hydrogensulfite;aluminum nickel; In water;
EXAMPLE 5 18.7 kg of sodium bisulfite were dissolved in 55.8 liters of water and the pH was adjusted to a pH of 9 to 9.5 with 14.4 kg of sodium hydroxide. To the solution were added 11.7 kg of raw 3-chloro-pyridine-N-oxide and the mixture was heated in an autoclave to 145 C. The reaction mixture was stirred at 145 C. for 17 hours (during the reaction, a pressure of 4 to 5 bars resulted). After completion of the reaction, cooling to 90 C. took place. 1 kg of sodium hydroxide (50 weight %) was added to adjust to alkaline and in a nitrogen atmosphere, 0.5 kg of Raney nickel were added. The suspension was heated to 100 to 110 C. and at this temperature, hydrogen was pressed on with 7 bars. Hydrogenation was carried out for 16 hours and then the mixture was cooled to 70 C. and the catalyst was separated with a pressure filter. The pyridine-3-sulfonic acid was isolated as in Example 4 and purified.
With hydrogenchloride; sodium hydroxide; dihydrogen peroxide; sodium sulfite;aluminum nickel; In ethanol; water; ethylene glycol; isopropyl alcohol;
EXAMPLE 6 252 g of sodium sulfite were dissolved in 700 of water and to this solution were added 129.6 g of raw 3-chloro-pyridine-N-oxide. In a nitrogen atmosphere, the reaction mixture was heated to 145 C. and stirred for 17 hours at this temperature. Subsequent cooling to 60 C. took place and 35 ml of ethanol, 35 g of sodium hydroxide (50%) and 14 g of Raney nickel were added. The suspension was again heated to 100 C. and hydrogenated at 7 bars for 6 hours. Cooling to 50 C. took place and the catalyst was filtered off. Sulfite still contained in the reaction solution was oxidized with 30 ml of hydrogen peroxide (70%) and at this point, approximately 400 ml of water were distilled from the reaction mixture in vacuo and 400 ml of glycol were added. Additional water was distilled off until the liquid phase temperature had risen to 100 C. Without further distillation, the temperature was increased to 130 C. by decreasing the vacuum. The hot suspension was filtered and the residue was washed with 100 ml of hot glycol. From the combined filtrate, glycol was distilled off until a residue remained which was still stirrable and which after cooling was mixted with 500 ml of concentrated hydrochloric acid and stirred for one hour at 35 C. Sodium chloride precipitate was filtered off and washed with 100 ml of concentrated hydrochloric acid. The filtrates were purified and concentrated to the limit of stirrability. Then, 300 ml of isopropanol were added at 80 C. The suspension was cooled to 20 C. and filtered. The filter cake was washed with 100 ml of isopropanol and the yield of the raw acid was 80 to 83%. For further purification, the product was dissoleved in 260 ml of water and after the addition of 5 g of activated charcoal (Eponit), stirring took place for 30 minutes at 80 C. followed by filtering. From the filtrate, approximately 170 ml of water were distilled off and after cooling to 70 C., 350 ml of ethanol were added. After cooling to 20 C., the precipitated pyridine-3-sulfonic acid was filtered off and then washed with 100 ml of methanol to obtain a yield of pure pyridine-3-sulfonic acid of between 77 to 80% with a purity of 99%.
With hydrogenchloride; bromine; In chloroform; water; acetone;
EXAMPLE 4 N-Ethyl 5-nitro-3-pyridinesulfonamide A mixture of 3g. of <strong>[636-73-7]3-pyridinesulfonic acid</strong> and 8.5g. of phosphorous pentachloride was heated at 120 C for 1.5 hours. Upon cooling to room temperature, the mixture solidified. Chloroform was added thereto and dry hydrogen chloride gas was introduced. The resulting precipitate was collected by filtration and dried. The crystalline substance obtained was heated with bromine (4g.) at 120 C. for 8 hours and water (60 ml.) was added to the mixture. After stirring at 80 C. for 2 hours, the solution was concentrated. On addition of acetone, 2g. of 5-bromo- <strong>[636-73-7]3-pyridinesulfonic acid</strong> was obtained.
With phosphorus pentachloride; potassium carbonate; In water; benzene;
EXAMPLE 49 To <strong>[636-73-7]pyridine-3-sulfonic acid</strong> (6 g) is added powdery phosphorus pentachloride (15.8 g) and the mixture is heated at 150 C. for 3 hours. The reaction mixture is concentrated under a reduced pressure at 60 to 70 C. and thereto is added anhydrous xylene. The mixture is concentrated under a reduced pressure and thereto is further added anhydrous xylene, and the mixture is again concentrated. To the resulting residue is gradually added water (20 ml) under cooling with dry ice-acetone to give a solution. The solution is added dropwise to a mixture of 1-hydroxy-1,2,3-benzotriazole (8.3 g), potassium carbonate (8.3 g), water (24 ml), benzene (40 ml) and ether (15 ml) at -2 to 0 C. with stirring. After the addition, to the mixture are added water (18 ml) and ether (15 ml) and the mixture is stirred at room temperature. The mixture is regulated at pH 7 to 8 with 1 N aqueous potassium hydroxide and then stirred for 2 hours. The reaction mixture is extracted with benzene-ether (240 ml). The extract is washed with a saturated aqueous sodium hydrogen carbonate and dried over potassium carbonate. After drying, the solvent is distilled off to give 1-(3-pyridylsulfonyloxy)-1,2,3-benzotriazole (7.2 g; 70%), melting point: 98 C. Anal. Calcd. for C11 H8 N4 O3 S: C, 47.82; H, 2.92; N, 20.28. Found. C, 47.99; H, 2.81; N, 20.29.
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