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CAS No. : | 90030-48-1 | MDL No. : | MFCD07776796 |
Formula : | C4H7NaO4S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | YICFALDKKMHFLT-UHFFFAOYSA-M |
M.W : | 174.15 | Pubchem ID : | 23665669 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.75 |
Num. rotatable bonds : | 4 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 30.62 |
TPSA : | 85.64 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -7.92 cm/s |
Log Po/w (iLOGP) : | -7.19 |
Log Po/w (XLOGP3) : | -0.78 |
Log Po/w (WLOGP) : | 0.29 |
Log Po/w (MLOGP) : | -0.54 |
Log Po/w (SILICOS-IT) : | -1.09 |
Consensus Log Po/w : | -1.86 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -0.16 |
Solubility : | 119.0 mg/ml ; 0.685 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.54 |
Solubility : | 50.2 mg/ml ; 0.288 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -0.19 |
Solubility : | 112.0 mg/ml ; 0.643 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.98 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302 | Packing Group: | N/A |
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 |
---|---|---|
95% | In dimethyl sulfoxide; at 20℃; | (b) Methyl 3-[4-([tert-butyl(dimethyl)silyl]oxy}methyI)benzyl]sulfonyl}propanoate<strong>[90030-48-1]SMOPS</strong> (1.76 g, 10.1 mmol, Wang et. al. Tetrahedron Letters 43, 2002, 8479-8483 ) was 5 dissolved in DMSO (20 mL) using a ultrazonic bath and was then added to tert-butyl[4- (chloromethyl)benzyl]oxy}dimethylsilane (2.4 g, 8.4 mmol) dissolved in DMSO (5 mL), and the reaction mixture was stirred at rt over night. Water (30 mL) was added and the mixture was extracted twice with EtOAc. The combined organics was dried over anhydrous Na2SO4, filtered and evaporated. 1H NMR indicated some DMSO left. ToI0 eliminate DMSO the crude product was dissolved in CH2Cl2 (40 mL), water (20 mL) was added and the two phase system was stirred for 30min. The organic layer was separated using a phase separator and evaporated to give methyl 3-[4-([tert- butyl(dimethyl)silyl]oxy}methyl)benzyl]sulfonyl}propanoate as a solid. Yield: 3.1 g (95%).15 MS m/z: 404 (NH+adduct). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
copper(l) iodide; In dimethyl sulfoxide; at 110℃; for 2.5h; | (2R, 4S)-4- { [3, 5-Bis (trifluoromethyl) benzyl]- (5-iodopyrimidin-2-yl)}- amino-2-ethyl-6-trifluoromethyl-3, 4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (1.69 g), <strong>[90030-48-1]sodium 3-methoxy-3-oxopropane-1-sulfinate</strong> (1.58 g), and copper (I) iodide (1.72 g) are dissolved in dimethylsulfoxide (20 ml), and the mixture is stirred at 110C under nitrogen atmosphere for 2.5 hours. The reaction solution is cooled to room temperature, and thereto are added water and ethyl acetate. The precipitated insoluble materials are removed by filtration through CeliteTM, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane : ethyl acetate = 4: 1---*2 : 1) to give (2R, 4S)- 4-[3, 5-bis (trifluoromethyl) benzyl]- [5- (2-methorcarbonylethanesulfonyl)- pyrimidin-2-yl] amino-2-ethyl-6-trifluoromethyl-3, 4-dihydro-2H-quinoline- 1-carboxylic acid ethyl ester (1.41 g). MS (m/z): 771 [M+H] + |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dimethyl sulfoxide; at 20℃; for 0.75h; | To a stirred solution of <strong>[90030-48-1]SMOPS</strong> (5.646 g, 0.0324 mol) in DMSO (dry, 50 niL) was added alpha-bromo-p-xylene (5 g, 0.027 mol) at r.t. and continued stirring for 45 min. The reaction mixture was extracted with EtOAc (4 x 100 mL), the organic layers were combined, driedanhydrous sodium sulphate and the solvents were removed in vacuo. The residue was redissolved in THF (100 mL) and methanol (25 mL) followed by addition of sodium methoxide (5.8 mL, 0.027 mol, 25%). After stirring for 15 min, the reaction mixture was concentrated and dissolved in water (10 mL). A solution of hydroxylamine-0-sulfonic acid (17.31g, 0.1350 mol) and sodium acetate (7g) in H2O (40 mL) was added to the reaction mixture which was stirred at r.t. for 12 h. The pH of the solution was adjusted to 9 by addition of aqueous bicarbonate solution and the mixture was extracted with EtOAc (3x50 ml), washed with brine, dried(Na2SO4), and the solvents were removed in vacuo. The residue thus obtained was treated with water (100 mL) and stirred for 10 min. Solid obtained was filtered and dried to afford l-(4-methylphenyl)methanesulfonamide. Yield= 3.3 g, (66 %). 1HNMR (300 MHz, DMSO-d6) delta 2.55(3H, s), 4.05(2H, s), 6.8 (2H,s), 7.1-7,3 (4H, m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dimethyl sulfoxide; at 20℃; for 0.666667h; | To a solution of <strong>[90030-48-1]SMOPS</strong> (4.8 g, 0.028 mol) in DMSO (dry, 50 mL) was added 2- bromomethyl pyridine HBr (5 g, 0.019 mol) at r.t.. After 40 min pH of the solution was adjusted to 8 by the addition of aqueous bicarbonate solution. The reaction mixture was extracted with EtOAc (4 x 100 mL), the organic layers were combined, dried over anhydrous sodium sulphate, filtered and the solvents were removed in vacuo. The residue was redissolved in a mixture of solvents consisting of THF (200 mL) and methanol (10 mL) and treated with a solution of sodium methoxide (4 mL, 25%) over a period of 10 min. After stirring for 40 min, the reaction mixture was concentrated in vacuo and dissolved in water (20 mL). Followed by addition of a solution of hydroxylamine-O- sulfonic acid (12.66 g, 0.099 mol), sodium acetate (7g) in water (60 mL) followed by stirring at r.t.. After 48 h pH of the solution was adjusted to 9 by the addition of aqueous bicarbonate solution and the mixture subjected to freeze drying. The solid thus obtained was treated with methanol, methanolic layer separated and concentrated. The residue was purified by flash chromatography on silica using a gradient of EtOAc in pet ether followed by EtOAc and then with MeOH in EtOAc to give l-Pyridin-2-ylmethanesulfonamide. Yield: 400 mg (12 %). EPO <DP n="184"/>1H NMR (400 MHz, DMSO-d6) delta 4.42-4.45 (2H, m), 6.90-6.95 (2H, m), 7.33-7.39 (IH, m), 7.45-7.50(1H3 m), 7.78-7.85 (IH, m), 8.53-8.59 (IH, m) MS m/z: 173 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16%; 42% | With copper(l) iodide; In dimethyl sulfoxide; at 130℃; for 1.5h; | A solution of l-(4-chloro-phenyl)-5-methyl-lH-pyrazole-4-carboxylic acid [l-(5-bromo- pyridin-3-yl)-butyl] -amide (1.1 g, 2.5 mmol), copper(I) iodide (1.4 g, 7.4 mmol), sodium 3-methoxy-3-oxopropane-l-sulfinate (1.3 g, 7.4 mmol) in DMSO (10 mL) is heated at 130 0C for 1.5 hour. After cooling to room temperature, saturated aqueous sodium ammonium chloride (10 mL) is added and the resultant mixture is stirred for 1 hour. The crude mixture is poured into saturated aqueous sodium bicarbonate (250 mL) and extracted with EtOAc (I x 250 mL, 2 x 100 mL). The combined organic layers are washed with brine (100 mL), dried over sodium sulfate, filtered and concentrated in vacuo. Purification by flash chromatography on silica gel (eluted with 25 to 75 % EtOAc/hexanes) affords l-(4-chloro-phenyl)-5-methyl-lH-pyrazole-4-carboxylic acid (1- pyridin-3-yl-butyl)-amide (159 mg, 16 %) and 3-[5-(l-{ [l-(4-chloro-phenyl)-5-methyl- lH-pyrazole-4-carbonyl]-amino}-butyl)-pyridine-3-sulfonyl]-propionic acid methyl ester (540 mg, 42 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; In dimethyl sulfoxide; at 110℃; for 0.583333h;Microwave irradiation; | To a solution of l-(4-fluorophenyl)-lH-pyrazolo[3,4-c]pyridine-4-carboxylic acid (6- bromopyridin-3-ylmethyl)-amide (150 mg, 0.35 mmol) in DMSO (2 niL) was added sodium 3-methoxy-3-oxopropane-l-sulfinate (125 mg, 0.717 mmol) followed by copper (I) iodide (135 mg, 0.708 mmol). The mixture was then warmed in a microwave at HO0C for 35 minutes. The reaction was monitored by TLC (EtOAc) indicating a new slightly more polar product than starting bromide. The reaction was then diluted with brine (10 mL) and extracted with EtOAc (4 x 10 mL). The combined organic layers were washed with brine (5 x 10 mL), dried over magnesium sulfate, filtered and concentrated. The solid was dissolved in dichloromethane and purified by silica gel chromatography eluting with EtOAc-dichloromethane (25:75, then 1:1, then 75:25). The material from the column was triturated with ether to afford the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of l-(4-fluoro-phenyl)- lH-pyrazolo[3,4-c]pyridine-4-carboxylic acid [1- (6-bromo-pyridin-3-yl)-cyclopropyl]-amide (0.250 g, 0.553 mmol), sodium 3- methoxy-3-oxopropane-l-sulfinate (289 mg, 1.66 mmol) and copper (I) iodide (316 mg, 1.66 mmol) in DMSO (2 mL) is placed in a microwave tube and evacuated and purged with argon three times. The reaction mixture is heated in a microwave at 110C for 2 hours, diluted with ethyl acetate (200 mL), washed with saturated aqueous ammonium chloride (4 x 100 mL), saturated aqueous sodium bicarbonate (100 mL), brine (100 mL), dried over MgS04, filtered and concentrated. The resulting residue is purified by silica gel chromatography eluting with a gradient of 50-100% ethyl acetate in heptane to afford the title compound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.46 g | With copper(l) iodide; In dimethyl sulfoxide; at 105℃; for 18.0h;Inert atmosphere; Sealed tube; | Methyl 3 -( 1 -((2-(trimemylsilyl)ethoxy)methyl)- 1 H-pyrrolo [2,3 -b]pyridin-5- ylsulfonvDpropanoate (4-lb) To a nitrogen gas purged sealable vial of 5-bromo-l-((2-( methylsilyl)ethoxy)methyl)-lH-pyrrolo[2,3-b]pyridine 4-la (3000 mg, 9.17 mmol), copper(i) iodide (6983 mg, 36.7 mmol) and sodium 3-methoxy-3-oxopropane-l-sulfinate(TYGER) (6385 mg, 36.7 mmol) was added DMSO (15 ml) . The reaction mixture was heated in an oil bath at 105c for 18hrs. LCMS analysis showed reaction to be a mixture of desired ester and acid. The reaction was quenched into ethyl acetate (200 ml) and water (200 ml) and the ph adjusted from 7 to 3 with IN HC1. The reaction was filtered thru celite and sand and the filtrate layers separated. The organic which contained a mix of acid and ester was dried over sodium sulfate, filtered and concentrated to an oil. The oil was azeotroped with toluene to remove any remaining water to give a brown oil, 3.4 gms. The oil was dissolved in dichloromethane (20 ml) and methanol (20.00 ml) cooled to 0C and TMS-Diazomethane (4.94 ml, 9.88 mmol) slowly added dropwise. The reaction was stirred at 0C for 10 minutes, quenched with aq. KHSO4 and allowed to stir at room temperature for 1 hr. The reaction was concentrated to remove methanol and the product extracted into ethyl acetate (100 ml), dried over sodium sulfate and concentrated to oil . The oil was chromatographed on silica (100 g, 0-50% ethyl acetate/hexanes) to give the product 4-lb as oil, 1.46 g . LRMS (ESI) m/z 399.1 [(M+H)+; calcd for C17H26N205SSi: 399.1 ]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; In dimethyl sulfoxide; at 110℃; | Step 2: Methyl 3-[(l -[ieri-butyl(dimethyl)silyl]oxy} -2,3-dihydro-lH-inden-5- yl)sulfonyl]propanoate[(5-bromo-2,3-dihydro-lH-inden-l -yl)oxy](/eri-butyl)dimethylsilane (1.62 g, 4.95 mmol), sodium 3-methoxy-3-oxopropane- l -sulfinate (3.45 g, 19.8 mmol) and Cul (3.77 g, 19.8 mmol) were charged in a scalable microwave flask. The flask was closed and degassed twice, after which dry DMSO (10 mL) was added and the reaction mixture was degassed before being heatedat 1 10C in an oil bath overnight. The reaction mixture was cooled and diluted with ethyl acetate (40 mL), filtered on a silica gel pad, and eluted with ethyl acetate. The organic solvents were concentrated under reduced pressure. The crude concentrate was purified on silica gel eluting with hexanes and ethyl acetate, then with DCM and methanol to afford the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; In dimethyl sulfoxide; at 110℃; | Step 2: Methyl 3-[l -(propan-2-ylsulfonyl)-lH-indazol-5-yl]sulfonyl}propanoate5-bromo-l -(propan-2-ylsulfonyl)-lH-indazole (0.85 g, 2.79 mmol), sodium 3- methoxy-3-oxopropane- l -sulfinate (2.42 g, 13.9 mmol) and Cul (2.66 g, 13.9 mmol) were charged in a sealable microwave flask. The flask was closed and degassed twice, after which dry DMSO (3.0 mL) was added and the reaction mixture degassed before being heated at 1 10C in an oil bath overnight. The reaction mixture was cooled and diluted with ethyl acetate (40 mL), and then filtered on a silica gel pad and eluted with ethyl acetate. The organic phases were concentrated under reduced pressure. The crude was purified on silica gel eluting with hexanes and ethyl acetate, then with DCM and methanol to afford the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; In dimethyl sulfoxide; at 110℃; | Step 1 : Methyl 3-(lH-indol-6-ylsulfonyl)propanoate6-bromo-lH-indole (3.0 g, 15.3 mmol), sodium 3-methoxy-3-oxopropane-l - sulfinate (8.0 g, 45.9 mmol) and Cul (14.6 g, 77.0 mmol) were charged to a sealable flask. The flask was closed and degassed twice, and then dry DMSO (30 mL) was added and the reaction mixture degassed again before being heated at 1 10C in an oil bath overnight. The reaction mixture was cooled and diluted with ethyl acetate (300 mL). The mixture was filtered on a silica gel pad and eluted with ethyl acetate. The organic phase was concentrated under reduced pressure. The crude was purified on silica gel eluting with hexanes and ethyl acetate, then with DCM and methanol to afford the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
309 mg | In dimethyl sulfoxide; at 20℃; for 18.0h; | Intermediate 7 Sodium 1 -methyl-3-sulfinopropanoate (282mg, 1.62mmol) was suspended in DMSO (2.5ml_). To this, (l -bromoethyl)benzene (0.185ml_, 1 .35mmol) was added and the mixture stirred at room temperature for 18 hours. The mixture was poured into water (25ml_) and extracted with diethyl ether. The organic layer was washed with brine, dried with Na2S04, filtered and concentrated in vacuo to give Intermediate 7 (309mg) as an oil. 1 H NMR (CDCIs) delta: 7.50-7.33 (5H, m), 4.23 (1 H, q), 3.68 (3H, s), 3.18-2.94 (2H, m), 2.83-2.56 (2H, m), 1 .80 (3H, d) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
107 mg | With copper(l) iodide; In dimethyl sulfoxide; at 130℃; for 2.5h;Inert atmosphere; | A solution of 1-(5-(4-chloro-2-fluorophenyl)-2-methyl-7,8-dihydro-[1 ,3,4]thiadiazolo- [2 3^2,3]imidazo[4,5-c]pyridin-6(5H)-yl)-2-((2-chloro-6-iodopyridin-3-yl)oxy)ethanone (150 mg), Cul (135 mg) and <strong>[90030-48-1]sodium 3-methoxy-3-oxopropane-1-sulfinate</strong> (124 mg) in DMSO (1.5 mL) was stirred at 130C for 2.5h. Sat. aq. NH4CI (5 mL) was added at rt and the mixture was stirred for 1 h. The mixture was diluted with EA and sat. aq. NaHC03. The layers were separated and the aq. phase was washed twice with EA. The combined org. layers were washed with aq. sat. NaCI, dried over MgS04, filtrated off and evaporated in vacuo. The crude was purified by FC (solvent: DCM/MeOH, 95/5) to afford 107 mg of a beige solid. LC- MS (A): tR = 0.88 min; [M+H]+: 642.49. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dimethyl sulfoxide; at 20℃; for 72.0h; | To a solution of 3-bromo-1-[(4-methoxyphenyl)methyl]pyrrolidin-2-one (2.50 g, 8.80 mmol) in dimethylsulfoxide (50 mL) was added <strong>[90030-48-1]sodium 1-methyl 3-sulfinopropanoate</strong> (1.53 g, 8.80 mmol) and the reaction was stirred at room temperature for three days. The solution was diluted with water (400 mL) and extracted with dichloromethane (2×250 mL). The combined organic layer was washed with water (150 mL), brine (100 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to afford crude methyl 3-({1-[(4-methoxyphenyl)methyl]-2-oxopyrrolidin-3-yl}sulfonyl)propanoate (2.5 g, 80.% yield). 1H NMR (300 MHz, CDCl3) ppm 2.31-2.45 (m, 1H), 2.65-275 (m, 1H), 2.85-3.05 (m, 2H), 3.26 (dt, J=9.4, 3.8 Hz, 1H), 3.41-3.50 (m, 1H), 3.74 (s, 3H), 3.79 (s, 3H), 3.77-3.92 (m, 2H), 4.01 (dd, J=10.2, 4.6 Hz, 1H), 4.44 (s, 2H), 6.87 (d, J=8.6 Hz, 2H), 7.16 (d, J=8.5 Hz, 2H). [M+H]+=356.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29.2% | With copper(l) iodide; In dimethyl sulfoxide; at 80℃;Inert atmosphere; | A mixture of 3-benzyloxy-6-bromo-2-nitro-pyridine (585 mg, 1.89 mmol) and <strong>[90030-48-1](3-methoxy-3-oxo-propyl)sulfinyloxysodium</strong> (329.5 mg, 1.892 mmol) in dimethylsulfoxide (5 mL) was purged with nitrogen for 2 minutes. Iodocopper (720.7 mg, 3.784 mmol) was added to the reaction mixture. The mixture was heated at 80 C. overnight, partitioned between ethyl acetate and a saturated aqueous solution of ammonium chloride. The resulting precipitate was removed by filtration and washed with ethyl acetate. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed three times with water, brine, dried over magnesium sulfate, filtered and concentrated to dryness. The crude material was purified by column chromatography (40-60% ethyl acetate in hexanes) to provide methyl 3-[(5-benzyloxy-6-nitro-2-pyridyl)sulfonyl]propanoate (210. mg, 0.552 mmol, 29.2%) as a pale yellow solid. 1H NMR (400 MHz, Chloroform-d) delta 8.20 (d, J=8.6 Hz, 1H), 7.68 (d, J=8.7 Hz, 1H), 7.50-7.31 (m, 5H), 5.35 (s, 2H), 3.75-3.63 (m, 5H), 2.87 (t, J=7.5 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With water; lithium hydroxide; In ethanol; at 110℃; | The salt of 3-sulfinopropionic acid (3spa) was prepared by saponification of the commercially available methyl ester [sodium1-methyl 3-sulfinopropanoate; Sigma Aldrich 7,78,168]. Briefly,<strong>[90030-48-1]sodium 1-methyl-3-sulfinopropanoate</strong> (100 mg, 0.57 mmol) was dissolved in 5 mL of deionized water. To this solution, LiOH (70 mg,2.9 mmol) was added prior to overnight reflux under constant stirring on an oil bath (~110 C). The solution was then cooled to~4 C, filtered and the filtrate was dried by rotary evaporation. The resulting solid was dissolved in 2 mL of cold ethanol and filtered again to remove inorganic salts. Evaporation of the ethanol filtrate gave the desired compound as a white solid (68 mg, 0.45 mmol,79%). Both 1H and 13C {1H} NMR were measured to verify the identity and relative purity of the 3spa product. 1H NMR (500 MHz,D2O) d 2.49 (t, J 7.8 Hz, 2H), 2.37 (t, J 7.8 Hz, 2H). 13C {1H} NMR(126 MHz, D2O) d 181.2, 57.3, 30.1 ppm. Additional confirmation of 3spa standard was performed by mass spectrometry as described elsewhere [18] with instrumentation from the Shimadzu Center for Advanced Analytical Chemistry (The University of Texas Arlington). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With copper(l) iodide; sulfuric acid; In dichloromethane; at 25℃; for 1.5h; | General procedure: In a test tube containing the appropriate sodium salt of sulfinic acid, 1a-c (0.5 mmol) and CuI (47.5 mg, 0.5 mmol) in dichloromethane (3 mL) was added sulfuric acid (200 L, 7.5 equiv.). The mixture was stirred for the time indicated on Scheme 1, then diluted with dichloromethane (10 mL) and transferred to a separation funnel. The mixture was then washed with water (2 x 20 mL) and the organic phase was dried over anhydrous MgSO4. The solvent was removed in vacuo to yield the corresponding thiosulfonates sufficiently pure for characterization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With sulfuric acid; In dichloromethane; at 25℃; for 12.5h;Molecular sieve; | General procedure: In a test tube containing the appropriate sodium salt of sulfinic acid, 1a-d (1 mmol) was added the appropriate alcohol (1 mL) followed by dichloromethane (4 mL) [For more complex alcohols, 3 equiv. (3 mmol) of alcohol were used]. Under stirring, sulfuric acid (106 mL, 2 equiv.) was added and after 30 min of reaction, powdered 4 A molecular sieves (200 mg) was added. The mixture was stirred for the time indicated on Table 2 and then diluted with dichloromethane (10 mL) and transferred to a separation funnel. The organic phase was then washed with water (2 x 20 mL), dried over anhydrous MgSO4 and filtered through a pad of silica. The solvents were removed in vacuo and the resulting crude product was further purified by flash column chromatography [hexanes:EtOAc (98:2)]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; In dichloromethane; at 25℃; for 15.5h;Molecular sieve; | General procedure: In a test tube containing the appropriate sodium salt of sulfinic acid, 1a-d (1 mmol) was added the appropriate alcohol (1 mL) followed by dichloromethane (4 mL) [For more complex alcohols, 3 equiv. (3 mmol) of alcohol were used]. Under stirring, sulfuric acid (106 mL, 2 equiv.) was added and after 30 min of reaction, powdered 4 A molecular sieves (200 mg) was added. The mixture was stirred for the time indicated on Table 2 and then diluted with dichloromethane (10 mL) and transferred to a separation funnel. The organic phase was then washed with water (2 x 20 mL), dried over anhydrous MgSO4 and filtered through a pad of silica. The solvents were removed in vacuo and the resulting crude product was further purified by flash column chromatography [hexanes:EtOAc (98:2)]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | With copper(l) iodide; In dimethyl sulfoxide; at 120℃; for 4.5h;Sealed tube; | ADMSO (0.5 mL) solution of Example 318 (20 mg, 39 tmol), <strong>[90030-48-1]sodium 3-methoxy-3-oxopropane-1-sulfinate</strong> (20 mg, 116 tmol) and copper(I) iodide (22 mg, 116.imol) was heated in a sealed safety vial at 120 C for 4.5 h. The resulting mixture wasdiluted with MeOH (1 mL) and filtered. The filtrate was purified via preparative LC/MS(Condition A: Gradient: 20-60% B over 20 minutes, then a 5-minute hold at 100% B) to give (R)-methyl 3 -((3 -(1 -((3 -chloro-6-(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)quinolin4-yl)amino)ethyl)-4-fluorophenyl)sulfonyl)propanoate (3 mg, 13% yield). LC/MS (M+H): 587; LC retention time: 1.87 mm (Method A). ?H NMR (500 MFIz, DMSO-d6) oe 9.26 (s, 2H), 8.75 (s, 1H), 8.49 (s, 1H), 8.18-8.11 (m, 2H), 8.00 (d,J=8.8 Hz, 1H), 7.80(br. s., 1H), 7.44 (t, J=9.3 Hz, 1H), 6.93 (d, J=8.5 Hz, 1H), 5.86-5.78 (m, 1H), 2.42-2.32 (m, 4H), 1.71 (d, J=6.7 Hz, 3H), 1.56 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With copper(l) iodide; In dimethyl sulfoxide; at 110℃;Microwave irradiation; Inert atmosphere; | To a 5-mL microwave vial were added 6-bromoquinoline (200 mg, 0.96 mmol), sodium 3- methoxy-3-oxopropane-1-sulfinate (0.84 g, 4.81 mmol), and Copper (I) iodide (0.92 g, 4.81 mmol) followed by DMSO (2 mL). The reaction was degassed (2x) with nitrogen then heated at 110oC overnight. After the reaction was cooled down room temperature, it was diluted with EtOAc. The resulting mixture was filtered through a pad of silica gel, washed with EtOAc, and then concentrated. The residue was purified by silica gel column chromatography to give the title compound (95 mg, 33%) as a yellow oil. LC/MS m/z = 280.2 [M+H]+;1H NMR (400 MHz, CD3OD) delta ppm 2.77 (t, J = 7.20 Hz, 2H), 3.55 (s, 3H), 3.65 (t, J = 7.20 Hz, 2H), 7.72 (dd, J = 8.46, 4.42 Hz, 1H), 8.17-8.22 (m, 1H), 8.24-8.29 (m, 1H), 8.61 (dd, J = 8.46, 1.14 Hz, 1H), 8.64 (d, J = 2.02 Hz, 1H), 9.07 (dd, J = 4.29, 1.77 Hz, 1H). |
With copper(l) iodide; In dimethyl sulfoxide; at 110℃;Inert atmosphere; | To a 5 mL microwave vial were added 6-bromoquinoline (200 mg, 0.96 mmol), sodium 3- methoxy-3-oxopropane-l-sulfinate (0.84 g, 4.81 mmol), and copper (I) iodide (0.92 g, 4.81 mmol) followed by DMSO (2 mL). The reaction was degassed (2x) with nitrogen then heated at 110 C overnight. After the reaction was cooled down room temperature, it was diluted with EtOAc. The resulting mixture was filtered through a pad of silica gel, washed with EtOAc, and then concentrated. The residue was purified by silica gel column chromatography to give the title compound (95 mg, 33% yield) as a yellow oil. LCMS m/z = 280.2 [M+H]+; NMR (400 MHz, CD3OD) delta ppm 2.77 (t, J = 7.20 Hz, 2H), 3.55 (s, 3H), 3.65 (t, / = 7.20 Hz, 2H), 7.72 (dd, / = 8.46, 4.42 Hz, 1H), 8.17-8.22 (m, 1H), 8.24-8.29 (m, 1H), 8.61 (dd, / = 8.46, 1.14 Hz, 1H), 8.64 (d, / = 2.02 Hz, 1H), 9.07 (dd, / = 4.29, 1.77 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With copper(l) iodide; In dimethyl sulfoxide; at 80℃; for 48h;Sealed tube; | methyl 4-bromo-1-methyl-pyrazole-3-carboxylate (508 mg, 2.319 mmol), (3-methoxy- 3-oxo-propyl)sulfinyloxysodium (810 mg, 4.651 mmol), and copper(1+) (Iodide Ion (1)) (1.31 g, 6.878 mmol) were combined in degassed DMSO (3.048 mL). Nitrogen was bubbled through the reaction for another 5 min and then it was sealed and heated to 80 C. The reaction was heated for 48 h then cooled to room temperature. The reaction was diluted with ethyl acetate (25 mL) and NH4Cl (10 mL). A thick precipitate formed which was filtered and discarded. The layers were separated and the organics were washed with a saturated NH4Cl (30 mL) solution, a satd NaHCO3solution (30 mL), and brine (30 mL). The organics were dried over sodium sulfate and evaporated. The crude material was purified by silica gel chromatography eluting with 0-100% ethyl acetate in hexanes to give methyl 4-(3-methoxy-3-oxo-propyl)sulfonyl-1-methyl-pyrazole-3- carboxylate (297 mg, 44%) ESI-MS m/z calc.290.05725, found 291.1 (M+1)+;Retention time: 0.32 minutes |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | In dimethyl sulfoxide; at 25℃; for 16.0h; | To a solution of 3-bromo-i-isopropylpyrrolidin-2-one (1 g, 4.85 mmol, 1 eq) in DMSO (10 mL) was added sodium 3-methoxy-3-oxo-propane-i-sulfinate (845 mg, 4.85 mmol, 1 eq). The mixture was stirred at 25 C for 16 hours. The reaction mixture was quenched with water (80 mL) and extracted with ethyl acetate (3 x 80 mL). The combined organic layers were washed with brine (60 mL), dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by column chromatography (Si02, petroleum ether : ethyl acetate = 10:1 to 1:1) to give the title compound (1.1 g, 3.97 mmol, yield 82 %). (1048) NMR (CDC13): delta = 4·37-4·33 (m, 1 H), 3·97-3·93 (m, 1 H), 3.82-3.72 (m, 5 H), 3.58- 3.51 (m, 1 H), 3·39-3·38 (m, iH), 2.94-2.90 (m, 2 H), 2.77-2.73 (m, 1 H), 2.44-2.34 (m, 1 H) and 1.18 (d, 6 H). (1049) LCMS: m/z 277.9 (M+H)+ (ES+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40 mg | With copper(l) iodide; In dimethyl sulfoxide; at 110℃; for 1.0h;Microwave irradiation; Sealed tube; | Compound 81-4 (50 mg, 0.14 mmol, 1.0 eq), compound 81-4a (71 mg, 0.41 mmol, 3.0 eq) and Cul (129 mg, 0.679 mmol, 5.0 eq) were taken up into a microwave tube in DMSO (1.5 mL). The sealed tube was heated at 110 C for 1 hour under microwave. The mixture was diluted with water (10 mL) and EA (30 mL). The suspension was filtered and the filtrate was separation, the water layer was extracted with EA (20 mL * 2). The combined organic layers were dried over Na2SC>4, filtered and concentrated to dryness under reduced pressure. The residue was purified by column chromatography over silica gel to afford the title compound 81-5 (40 mg, 75% yield). LCMS (ESI): RT = 0.813 min, mass calcd. for (1094) C18H24N4O4S 392.15, m/z found 393.0 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60 mg | With copper(l) iodide; In dimethyl sulfoxide; at 110℃; for 1.0h;Microwave irradiation; Sealed tube; | Compound 89-4 (60 mg, 0.16 mmol, 1.0 eq) , compound 89-4a (85 mg, 0.49 mmol, 3.0 eq) and Cul (155 mg, 0.815 mmol, 5.0 eq) were taken up into a microwave tube in DMSO (1.5 mL). The sealed tube was heated at 110 C for 1 hour under microwave. The mixture was diluted with water (10 mL) and EA (30 mL).The suspension was filtered and the filtrate was separation, the water layer was extracted with EA (20 mL * 2). The combined organic layers were dried over Na2SC>4, filtered and concentrated to dryness under reduced pressure. The residue was purified by column chromatography over silica gel to afford compound 89-5 (60 mg, 94% yield). LCMS (ESI): RT = 0.748 min, mass calcd. for (1172) C18H24N4O4S 392.15, m/z found 393.0 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With copper(l) iodide; In dimethyl sulfoxide; at 110℃; for 1.0h;Microwave irradiation; Sealed tube; | Compound 116-2 (130 mg, 0.335 mmol, 1.0 eq), compound 116-2a (175 mg, 1.00 mmol, 3.0 eq) and Cul (319 mg, 1.67 mmol, 5.0 eq) were taken up into a microwave tube in DMSO (3 mL). The sealed tube was heated at 110 C for 1 hour under microwave. The mixture was diluted with water (10 mL) and EA (30 mL). The suspension was filtered and the filtrate was separation, the water layer was extracted with EA (20 mL * 2). The combined organic layers were dried over Na2SC>4, filtered and concentrated to dryness under reduced pressure. The residue was purified by column chromatography over silica gel to afford the title compound 116-3 (110 mg, 80% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With copper(l) iodide; In dimethyl sulfoxide; at 110℃;Inert atmosphere; | Intermediate 40 (S)-4-(6-bromo-4-((methylsulfonyl)methyl)pyridin-2-yl)-3-ethylmorpholine (500 mg, 1.376 mmol), copper(I) iodide (0.5 g, 2.63 mmol) and 3-methoxy-3-oxopropane-1-sulfinate, Sodium salt (0.500 g, 2.87 mmol, Aldrich) were placed in Dimethyl Sulfoxide (DMSO) (4 ml.) and degassed under N2 gas for 20 minutes. The resulting reaction mixture was heated to 110 C under an atmosphere of N2 for 1 hour. EtOAc (50 ml.) was added to the cooled reaction mixture and the organic layer was washed with water, aqueous saturated NaHC03, aqueous saturated ammonium chloride (3 x 50 ml. 2:2: 1). The organic layers were combined, filtered through a hydrophobic frit and concentrated in vacuo to give a brown oil. The crude product was purified by column chromatography on Silica eluting with EtOAc: Cyclohexane (60-100%). The relevant fractions were combined and concentrated in vacuo to give methyl (S)-3-((6-(3-ethylmorpholino)-4- ((methylsulfonyl)methyl)pyridin-2-yl)sulfonyl)propanoate (550 mg, 1.266 mmol, 92% yield) as an orange oil. LCMS (System A, UV, ESI): Rt = 0.83 min, [M+H]+ 435 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With copper(l) iodide; In dimethyl sulfoxide; at 110℃; for 2.0h;Inert atmosphere; | A mixture of Intermediate 41 (S)-4-(6-bromo-4-(4-(methylsulfonyl)tetrahydro-2H-pyran-4- yl)pyridin-2-yl)-3-ethylmorpholine (28.76g, 66.4 mmol), <strong>[90030-48-1]sodium 3-methoxy-3-oxopropane-1-sulfinate</strong> (15.02 g, 86 mmol, Aldrich) and copper(I) iodide (16.43 g, 86 mmol) in Dimethyl Sulfoxide (DMSO) (130 ml.) was heated to 110C under nitrogen for 2 hours. The reaction mixture was separated between ethy acetate (600ml) and a dilute solution of ammonia (700ml). The aquous phase was extracted using ethyl acetate (200ml). The combined organic phases were washed with brine (300ml) and dried over magnesium sulphate. The solvent was removed in vacuo. To the residue was added TBME (250ml). The solid was collected by filtration, but started to gum on the filter paper. The solid was dissolved in and combined with the filtrate. This was evaporated in vacuo to give (S)-methyl 3-((6-(3- ethylmorpholino)-4-(4-(methylsulfonyl)tetrahydro-2H-pyran-4-yl)pyridin-2-yl)sulfonyl)propanoate (30.59g, 91%) as a light brown solid/gum. LCMS (System B, UV, ESI): Rt = 0.83 min, [M+H]+ 505 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With copper(l) iodide; In dimethyl sulfoxide; at 110℃; for 2.0h;Inert atmosphere; Sealed tube; | <strong>[90030-48-1]sodium 3-methoxy-3-oxopropane-1-sulfinate</strong> (107 mg, 0.616 mmol, Aldrich), copper(I) iodide (117 mg, 0.616 mmol), Intermeduate 48 tert-butyl (S)-4-(2-bromo-6-(3-ethylmorpholino)pyridin-4- yl)-4-(methylsulfonyl)piperidine-1-carboxylate (164 mg, 0.308 mmol) were placed in Dimethyl Sulfoxide (DMSO) (2500 pi) and the resulting mixture was degassed under a flow of nitrogen for 5 min, sealed and heated to 110 C for 2h. EtOAc (80 ml.) was added to the cooled reaction mixture and the resulting mixture was washed with watensaturated ammonium chloride : saturated sodium bicarbonate (1: 1: 1, 2 x 90 ml_), brine (30 ml.) and dried over MgS04. The volatiles were removed under reduced pressure to give a residue that was purified by column chromatography to give tert-butyl (S)-4-(2-(3-ethylmorpholino)-6-((3-methoxy-3- oxopropyl)sulfonyl)pyridin-4-yl)-4-(methylsulfonyl)piperidine-1-carboxylate (150 mg, 0.248 mmol, 81% yield). LCMS (System B, UV, ESI): Rt = 1.08 min, [M+H]+ 604 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium iodide; In acetonitrile; at 80℃; | Intermediate 55 (S)-4-(6-bromo-4-(bromomethyl)pyridin-2-yl)-3-ethylmorpholine (354 mg, 0.972 mmol), <strong>[90030-48-1]sodium 3-methoxy-3-oxopropane-1-sulfinate</strong> (207 mg, 1.189 mmol, Sigma Aldrich), potassium iodide (48 mg, 0.289 mmol), and Acetonitrile (7 ml.) were combined in a microwave vial which was heated at reflux for 1.5 h. The reaction mixture was partitioned between sat. sodium bicarbonate solution (50 ml.) and EtOAc (50ml_). The organic layer was dried over a hydrophobic frit, and concentrated in vacuo to give methyl (S)-3-(((2-bromo-6-(3-ethylmorpholino)pyridin-4- yl)methyl)sulfonyl)propanoate (460 mg, 1.057 mmol, 109% yield) as a light brown gum. LCMS (System A, UV, ESI): Rt = 1.12 min, [M+H]+ 435 + 437 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With copper(l) iodide; In dimethyl sulfoxide; at 110℃; for 2.0h;Inert atmosphere; | A solution of Intermediate 67 tert-butyl ((5-bromo-1H-pyrrolo[3,2-b]pyridin-2- yl)methyl)(methyl)carbamate (1.1912 g, 3.50 mmol), <strong>[90030-48-1]sodium 3-methoxy-3-oxopropane-1-sulfinate</strong> (1.224 g, 7.03 mmol, Aldrich) and copper(I) iodide (1.34 g, 7.04 mmol) in Dimethyl Sulfoxide (DMSO) (18 ml) was degassed for 10 minutes under a flow of nitrogen. The reaction vessel was heated to 110 C and stirred at 110 C under nitrogen for 2h. Ethyl acetate (30 ml) was added to the reaction mixture, which was then filtered on Celite (lOg) and the residual solid washed with ethyl acetate (3x20 ml). The filtrate was washed with a mixture of water/aqueous saturated ammonium chloride / aqueous saturated sodium bicarbonate (4: 1: 1 60 ml), and water (60 ml). The aqueous layer was further extracted with ethyl acetate (50 ml) and the organic phases combined. The organic phase was further washed with a mixture of water/aqueous saturated ammonium chloride / aqueous saturated sodium bicarbonate (4: 1: 1 60 ml), and water (60 ml), followed by brine (50 ml), dried over magnesium sulfate and concentrated under reduced pressure to yield methyl 3-((2- (((tertbutoxycarbonyl)(methyl)amino)methyl)-1H-pyrrolo[3,2-b]pyridin-5-l)sulfonyl)- propanoate (1380 mg, 3.35 mmol, 96% yield). LCMS (System B, UV, ESI): Rt = 0.92 min, [M+H]+ 412 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With copper(l) iodide; In dimethyl sulfoxide; at 80 - 110℃; for 38.0h;Inert atmosphere; Sealed tube; | (4-Bromo-l-methyl-pyrazol-3-yl)-trimethyl-silane (141 mg, 0.60 mmol), (3- methoxy-3-oxo-propyl)sulfmyloxysodium (211 mg, 1.21 mmol) and copper(I) iodide (350 mg, 1.84 mmol) were combined in degassed DMSO (850 pL). Nitrogen was bubbled through the reaction for another 5 min and then it was sealed and heated to 80 C for 16 hours, giving only low conversion. The reaction temperature was increased to 110 C for 22 hours and during this time the reaction went from a cloudy brown solution to a clear orange, and finally a dark black. The reaction was cooled to room temperature and diluted with ethyl acetate (25 mL) and NH4Cl (10 mL). The aqueous was extracted with 2 x 20 mL ethyl acetate and the combined organics were washed with brine (30 mL). The organics were dried over sodium sulfate and evaporated. The crude material was purified by silica gel chromatography eluting with 0-100% ethyl acetate in hexanes to give methyl 3-(l-methyl-3-trimethylsilyl-pyrazol-4-yl)sulfonylpropanoate (40 mg, 22%). NMR (400 MHz, Chloroform-d) d 7.87 (s, 1H), 3.96 (s, 3H), 3.67 (s, 3H), 3.47 - 3.36 (m, 2H), 2.78 (dd, J = 8.3, 7.1 Hz, 2H), 0.38 (s, 9H). ESI-MS m/z calc. 304.0913, found 305.6 (M+l)+; Retention time: 0.54 minutes (LC method D). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With copper(l) iodide; L-proline; In dimethyl sulfoxide; at 130℃; for 16.0h; | Copper(I) iodide (0.19 g, 0.0010 mol) was added to a solution of 4-((8-(6-bromo-4- fluorobenzo[d]thiazol-2-yl)-8-azabicyclo[3.2.l]octan-3-yloxy)methyl)-5-cyclopropyl-3-(2- (trifluoromethoxy)phenyl)isoxazole (0.65 g, 0.0010 mol), sodium 3-methoxy-3-oxopropane- l-sulfinate (0.35 g, 0.0020 mol ) and L-proline (0.117 g, 0.0010 mol) in dimethylsulfoxide (13 ml) at room temperature and the resulting mixture warmed to 130 C. After 16 h, water and ethyl acetate were added and the mixture filtered through celite. The filtrate was then washed with cold water, brine, dried over anhydrous Na2S04, filtered, concentrated under reduced pressure and purified by flash column chromatography using silica gel 100-200 mesh, eluting with 0-70% ethyl acetate in petroleum ether to afford the titled compound (0.15 g, 20 %) as a solid. LC-MS: 2.50 mins, [M+H]+ 710 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | With copper(l) iodide; L-proline; In dimethyl sulfoxide; at 130℃; for 16.0h; | Cu(I)I (570 mg, 3.02 mmol) was added to a solution of 4-((8-(6-bromo-4- methylbenzo[d]thiazol-2-yl)-8-azabicyclo[3.2.l]octan-3-yloxy)methyl)-5-cyclopropyl-3-(2- (trifluoromethoxy)phenyl)isoxazole_(960 mg, 1.51 mmol), sodium 3-methoxy-3-oxopropane- 1-sulfinate (790 mg, 4.54 mmol ) and L-proline (174 mg, 1.51 mmol) in dimethylsulfoxide (20 ml) at room temperature and the resulting mixture warmed to 130 C. After 16 h, water and ethyl acetate were added and the mixture filtered through celite. The filtrate was then washed with cold water, brine, dried over anhydrous Na2S04, filtered, concentrated under reduced pressure and purified by flash column chromatography using silica gel 100-200 mesh, eluting with 0-65% ethyl acetate in petroleum ether to afford the titled compound (0.25 g, 25 %) as a solid. LC-MS: 2.57 mins, [M+H]+ 706 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | With copper(l) iodide; L-proline; In dimethyl sulfoxide; at 130℃; for 16.0h; | (0296) Copper(I) iodide (0.96 g, 5.16 mmol) was added to a solution of l-(3-bromophenyl)-3- (2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)azetidin-3- ol (1.6 g, 2.58 mmol), sodium 3-methoxy-3-oxopropane-l-sulfinate (1.34 g, 7.74 mol) and L- proline (0.28 g, 2.4 mmol) in dimethylsulfoxide (32 ml) to room temperature. The resulting mixture was stirred at 130 C for 16 h then partitioned with water and ethyl acetate before being filtered through celite. The combined organic layers were washed with cold water and brine solution, dried over anhydrous Na2S04, filtered, concentrated under reduced pressure and purified by silica gel column chromatography eluting with 0-60 % ethyl acetate in petroleum ether to afford the titled compound (320 mg, 18 %) as a solid. LC-MS: 2,35mins, [M+H]+ 691 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | With copper(l) iodide; L-proline; at 130℃; for 16.0h; | Copper(I) iodide (0.87 g, 0.0046 mol) was added to a solution of 3-(4-bromophenyl)- l-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4- yl)methoxy)phenyl)cyclobutanol (1.2 g, 0.0022 mol), sodium 3-methoxy-3-oxopropane-l- sulfinate (0.8 g, 0.0046 mol) and L-proline (1.05 g, 0.0092 mol) in dimethylsulfoxide (12 ml) at room temperature. The resulting mixture was stirred at 130 C for 16 h before being partitioned with water and ethyl acetate. After filtering through celite the organic layer was washed with cold water, brine, and purified by silica gel column chromatography eluting with 0-70 % ethyl acetate in petroleum ether to afford the titled compound (210 mg, 16 %) as a solid. LC-MS: 2.40 mins, [M+H]+ 690 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | With copper(l) iodide; L-proline; In dimethyl sulfoxide; at 130℃; for 16.0h; | Copper(I) iodide (458 mg, 2.41 mmol) was added to a solution of 4-((4-(2-(4- bromophenyl)cyclopropyl)-3 -chlorophenoxy)methyl)-5-cyclopropyl-3 -(2,6- dichlorophenyl)isoxazole (710 mg, 1.20 mmol), sodium 3-methoxy-3-oxopropane-l-sulfinate (629 mg, 3.6 mmol ) and L-proline (138 mg, 1.20 mmol) in dimethylsulfoxide (10 ml) at room temperature and the resulting mixture heated at 130 C. After 16 h the reaction was portioned with water and ethyl acetate before filtering through celite. The organic layer washed with cold water, brine, dried over anhydrous Na2S04, filtered, concentrated under reduced pressure and purified using silica gel column chromatography, eluting with 0-50% pet ether and ethyl acetate to afford the titled compound (210 mg, 26 %) as a solid. LC-MS: 2.50 mins, [M+H]+ 680 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | With copper(l) iodide; In dimethylsulfoxide-d6; at 110℃; for 15h;Inert atmosphere; | A mixture of <strong>[10386-27-3]2-bromopyridine-4-carbonitrile</strong> (4.4 g, 24.04 mmol, 1 eq), sodium 3- methoxy-3-oxo-propane-1-sulfinate (5.02 g, 28.85 mmol, 1.2 eq), CuI (5.49 g, 28.85 mmol, 1.2 eq) in DMSO (50 mL) was degassed and purged with nitrogen for three times, and then the mixture was stirred at 110 C for 15 h under nitrogen atmosphere. The mixture was then cooled to room temperature, diluted with ethyl acetate (50 mL) and filtered through a pad of silica. The filtrate was washed by water (2 x 20 mL), brine (20 mL), dried over anhydrous sodium sulfate, filtered through a pad of silica and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO; 20 g Sepa Flash Silica Flash Column, Eluent of 0~100% Ethyl acetate/Petroleum ether gradient 35 mL/min). Compound methyl 3-[(4-cyano-2-pyridyl)sulfonyl]propanoate (3 g, 11.80 mmol, 49% yield) was obtained as a white solid. MS: m/z = 254.9 (M+1, ESI+). |
Tags: 90030-48-1 synthesis path| 90030-48-1 SDS| 90030-48-1 COA| 90030-48-1 purity| 90030-48-1 application| 90030-48-1 NMR| 90030-48-1 COA| 90030-48-1 structure
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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.
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