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Chemical Structure| 1083327-58-5

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Product Details of [ 1083327-58-5 ]

CAS No. :1083327-58-5
Formula : C7H9BrN2O3S
M.W : 281.13
SMILES Code : CS(=O)(NC1=CC(Br)=CN=C1OC)=O
MDL No. :MFCD22989195

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Application In Synthesis of [ 1083327-58-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1083327-58-5 ]

[ 1083327-58-5 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 3144-09-0 ]
  • [ 578007-66-6 ]
  • [ 1083327-58-5 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate;copper(l) iodide; In water; N,N-dimethyl-formamide; at 105℃; for 20.0h; EXAMPLE 119; N-(2-Methoxy-5-(4-morpholinoquinolin-6-yl)pyridin-3- yl)methanesulfonamide; (1) N-(5-Bromo-2-methoxypyridin-3-yl)methanesulfonamide.; To a 5 mL microwave vial, <strong>[578007-66-6]5-bromo-3-iodo-2-methoxypyridine</strong> (0.317 g, 1.01 mmol, Alfa Aesar, Ward Hill, MA), methanesulfonamide (0.100 g, 1.06 mmol), cesium carbonate (0.829 g, 2.54 mmol) and copper(I) iodide (0.0211 g, 0.111 mmol) were mixed into DMF (1 mL). water (0.1 mL) was added and the mixture was heated at 105 0C for 20 h. The reaction mixture was poured into water/Tris-lM HCl pH 7 buffer then IN HCl was added to bring pH to ~5. The aqueous phase was extracted with EtOAc (3 X 20 mL). The combined organic phases were washed with saturated aqueous NaCl (40 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (eluent: EtOAc in hexanes 0 % - 50 %) to afford an off white solid (0.135 g) as the desired product. MS (ESI pos. ion) m/z calcd for C7H9BrN2O3S: 280.0; found 280.8/282.8 [M+l/M+3]. 1H NMR (300 MHz, CHLOROFORM-^), delta ppm 3.04 (s, 3 H) 3.92 - 4.07 (m, 3 H) 6.74 (br. s., 1 H) 7.89 (d, J=2.19 Hz, 1 H) 7.97 (d, J=2.19 Hz, 1 H).
  • 2
  • [ 1083327-58-5 ]
  • [ 73183-34-3 ]
  • [ 1083326-75-3 ]
YieldReaction ConditionsOperation in experiment
74% A suspension of N-(5-bromo-2-methoxypyridin-3-yl)methanesulfonamide (3.35 g, 11.9 mmol) and 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (4.24 g, 16.7 mmol, Beijing datianfengtuo) in toluene (100 mL) was degassed and charged with N2 for 3 times, then Pd(dba)3 (616 mg, 0.595 mmol, Matthey) and PPh3 (243 mg, 0.892 mmol) were added. The mixture was heated to 45 C. and stirred for 45 minutes, then KOAc (3.74 g, 23.8 mmol) was added. The resulted mixture was heated to reflux and stirred further for 3 hours, then cooled to rt, diluted with EtOAc (100 mL), and filtered through a CELITE. The filtrate was washed with water (70 mL*3) and brine (100 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (v/v)=2/1) to give the title compound as a white solid (2.90 g, 74%). MS (ESI, pos. ion) m/z: 328.9 [M+H]+; 1H NMR (600 MHz, CDCl3): delta 8.32 (d, J=1.4 Hz, 1H), 8.06 (d, J=1.3 Hz, 1H), 6.66 (brs, 1H), 4.05 (s, 3H), 3.02 (s, 3H), 1.33 (s, 12H).
72% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 4h;Inert atmosphere; General procedure: A mixture of 16a (11.38 g, 30 mmol), bis(pinacolato)diboron (9.14 g, 36 mmol) and potassium acetate (5.89 g, 60 mmol) in 1,4-dioxane (200 mL) was degassed, and then PdCl2(dppf) (1.1 g, 1.5 mmol) was added. The reaction mixture was degassed and back-filled with argon (three cycles), stirred at 100 C under argon atmosphere for 4 h, and then cooled to room temperature. The resulting mixture was filtered and the filtrate was concentrated and purified with column chromatography (silica gel, PE/EtOAc = 7:1) to afford 17a as a pale yellow solid (12.69 g, 99% yield).
60.4% With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium acetate; In N,N-dimethyl-formamide; at 100℃; for 8h;Inert atmosphere; A solution of the 2a (2.80 g, 10 mmol), bis(pinacolato)diborane(1.27 g, 5 mmol), Pd(dppf)2Cl2 (0.18 g, 0.25 mmol) and KOAc (1.47 g,15 mmol) in anhydrous DMF (30 ml) under N2 was stirred at 100 Cfor 8 h. DMF was removed under reduced pressure and add water(100 ml), extracted with ethyl acetate (3 100 ml), the organiclayer was washed with water (20 ml), dried with Na2SO4 andevaporated to give compound 3a as a white solid (1.98 g, 60.4%yield). mp 90e92 C. 1H NMR (400 MHz, DMSO) d 9.25 (s, 1H, NH),8.21 (d, J 1.6 Hz, 1H, Ar-H), 7.78 (d, J 1.6 Hz, 1H, Ar-H), 3.94 (s, 3H,OCH3), 3.01 (s, 3H, CH3), 1.30 (s, 12H, CH3). ESI-MS: m/z 329.1[MH].
60.4% With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; potassium acetate; In N,N-dimethyl-formamide; at 100℃; for 8h;Inert atmosphere; A solution of the 2a(2.80 g, 10 mmol), bis(pinacolato)diborane (1.27 g, 5 mmol), Pd(dppf)2Cl2 (0.18 g, 0.25 mmol) and KOAc (1.47 g, 15 mmol) inanhydrous DMF (30 ml) under N2 was stirred at 100 C for 8 h.DMF was removed under reduced pressure and adding water(100 ml), extracted with ethyl acetate (3 100 ml), the organiclayer was washed with water (20 ml), dried with Na2SO4 and evaporatedto give compound 3a as a white solid (1.98 g, 60.4% yield).Mp 90-92 C. 1H NMR (400 MHz, DMSO) d 9.25 (s, 1H, NH), 8.21(d, J = 1.6 Hz, 1H, Ar-H), 7.78 (d, J = 1.6 Hz, 1H, Ar-H), 3.94 (s, 3H,OCH3), 3.01 (s, 3H, CH3), 1.30 (s, 12H, CH3). ESI-MS: m/z 329.1 [M+H]+.
60.4% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 100℃; for 8h;Inert atmosphere; General procedure: A solution of the 5a (2.80 g, 10 mmol), bis(pinacolato)diborane(1.27 g, 5 mmol), Pd(dppf)2Cl2 (0.18 g, 0.25 mmol) and KOAc (1.47 g,15 mmol) in anhydrous DMF (30 ml) under N2 was stirred at 100 C for8 h. Then DMF was removed under reduced pressure and add water(100 ml), extracted with ethyl acetate (200 ml) for two times, dried with anhydrous Na2SO4 and evaporated to get the residue which was purified through a column chromatography on silica with petroleum ether / ethyl acetate (V:V 5:1) to give compound 6a as a white solid(1.98 g, 60.4% yield). mp 90-92 C. 1H NMR (400 MHz, DMSO-d6) delta9.25 (s, 1H, NH), 8.21 (d, J=1.6 Hz, 1H, Ar-H), 7.78 (d, J=1.6 Hz,1H, Ar-H), 3.94 (s, 3H, OCH3), 3.01 (s, 3H, CH3), 1.30 (s, 12H, CH3).ESI-MS: m/z 329.1 [M+H]+.
With potassium acetate;tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In toluene; at 90℃; for 1.16667h;Inert atmosphere; Intermediate 16W-(2-Methoxy-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-3- ideAll weights, volumes and equivalents are relative to A/-(5-bromo-2-methoxypyridin-3- yl)methanesulfonamide.Tricyclohexylphosphine (0.1 191 g, 0.425 mmol, 0.008eq, 0.008wt) and Pd2(dba)3 (0.1438 g, 0.157 mmol, 0.003 eq, 0.01 wt) are mixed together and then toluene (15.00 mL, 1 vol, 0.86wt, sparged with nitrogen for 1 hr) is added. The mixture is stirred and heated to 40- 45C for 45 mins before being allowed to cool back to room temp and sit under nitrogen to give an orange-gold solution with suspended black particulates. In a separate vessel, N- (5-bromo-2-methoxypyridin-3-yl)methanesulfonamide (15.0323 g, 53.5 mmol, 1 wt, 1 eq), bis(pinacolato)diboron (16.2962 g, 64.2 mmol, 1 .2 eq, 1.08 wt) and potassium acetate (10.4879 g, 107 mmol, 2 eq, 0.70 wt) are mixed together with toluene (150 mL, 10 vols, 8.6 wt). The resultant slurry is stirred and heated to 90 C under a flow of nitrogen. Having reached the desired temperature, the catalyst mixture is added over 10 minutes followed by a wash of toluene (7.50 mL, 0.5 vol, 0.43 wt). The mixture is stirred at 90 C for at least one hour and then sampled for HPLC analysis. Once complete, the reaction mixture is cooled to 50 C and filtered to remove inorganic material. The filtered solid is washed with toluene (2 x 15 mL, 2 x 1 vol, 2 x 0.86 wt) and the liquors and washes combined and distilled down to 5 vols. The product solution is allowed to cool to room temperature by which stage it has become a slurry. Heptane (75 mL, 5 vols, 3.4 wt) is slowly added to the slurry. The slurry is aged and the supernatant analysed by HPLC to ensure sufficient crystallisation has occurred. The slurry is filtered and the solid product is washed with 1 : 1 toluene: heptane (2 x 15mL, 2 x 1vol) and dried under vacuum at 40-50 C to afford N-(2- methoxy-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-3-yl)methanesulfonamide as an off-white solid.
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; N,N-dimethyl-formamide; at 110℃; for 2h;Sealed tube; Inert atmosphere; General procedure: The following is based on a modified literature procedure (Knight S. D. et al., ACS Med. Chern. Let., 2010, 1, 39-43 and W02008 150827). To N-(5-bromo-2-methoxypyridin-3 -yI)methanesulphonamide(350 mg, 1.24 mmol) in dry 1,4-dioxane (9 mL)/dry DMF (1 mL) in a sealed tube was added, bis(pinacolato)diboron (347 mg, 1.37 mmol), KOAc (366 mg, 3.73 mmol), and the whole mixture was degassed and purged with N2. Pd(dppf)C12.CH2C12 (52 mg, 0.06mmol) was then added with vigorous stirring and the mixture heated to 110C for 2 h. The disappearance of the starting bromide was monitored by LRMS. This mixture was then allowed to cool to room temperature and used in situ without further purification. LRMS (APCI) calcd for C13H21BN205S 330 (M1-I), found 330 (boronate ester).
All weights, volumes and equivalents are relative to N-(S30 bromo-2-methoxypyridin-3-yl)methanesulfonamide.Tricyclohexylphosphine (0.1191 g, 0.425 mmol, 0.008 eq,0.008 wt) and Pd2(dba)3 (0.1438 g, 0.157 mmol, 0.003 eq,0.01 wt) are mixed together and then toluene (15.00 mE,vol, 0.86 wt, sparged with nitrogen for 1 hr) is added. Themixture is stirred and heated to 40-45 C. for 45 mins beforebeing allowed to cool back to room temp and sit under nitrogen to give an orange-gold solution with suspended blackparticulates. In a separate vessel, N-(S -bromo-2-methoxypy-ridin-3-yl)methanesulfonamide (15.0323 g, 53.5 mmol, 1 wt,eq), bis(pinacolato)diboron(16.2962 g, 64.2 mmol, 1.2 eq,1.08 wt) and potassium acetate (10.4879 g, 107 mmol, 2 eq,0.70 wt) are mixed together with toluene (150 mE, 10 vols,8.6 wt). The resultant slurry is stirred and heated to 90 C.under a flow ofnitrogen. Having reached the desired temperature, the catalyst mixture is added over 10 minutes followedby a wash oftoluene (7.50 mE, 0.5 vol, 0.43 wt). The mixtureis stirred at 90 C. for at least one hour and then sampled forHPEC analysis. Once complete, the reaction mixture iscooled to 50 C. and filtered to remove inorganic material.The filtered solid is washed with toluene (2x1 S mE, 2x 1 vol,2x0.86 wt) and the liquors and washes combined and distilleddown to S vols. The product solution is allowed to cool toroom temperature by which stage it has become a slurry.Heptane (75 mE, S vols, 3.4 wt) is slowly added to the slurry.The slurry is aged and the supernatant analysed by HPEC toensure sufficient crystallisation has occurred. The slurry isfiltered and the solid product is washed with 1:1 toluene:heptane (2x1 S mE, 2x1 vol) and dried under vacuum at40-S0 C. to afford N-(2-methoxy-S-(4,4,S,S-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methanesulfonamide asan off-white solid.Recrystallisation-All weights, volumes and equivalentsare relative to N-(2-methoxy-S-(4,4,S,S-tetramethyl- 1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methanesulfonamide.A stirred suspension of N-(2-methoxy-S-(4,4,S,S-tetram-ethyl-i ,3,2-dioxaborolan-2-yl)pyridin-3-yl)methane-sulfonamide (1 wt, 1.01 kg) in propan-2-ol (4 vol, 4.OS E) isheated to 70-75C. under a nitrogen atmosphere, then aged atthis temperature for at least 2 hr. The batch is allowed to cool to 20-25 C. over at least 1 hr, then the suspension is aged at this temperature for a further 1 hr. The liquors are sampled by HPLC to ensure complete crystallisation, then the resulting solids are filtered, washed with propan-2-ol (2x1 vol, 2x1.01 L) before being sucked dry for 0.5 hr, then the batch is dried in vacuo at 50 C. to constant probe temperature to afford N-(2-methoxy-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl)pyridin-3-yl)methanesulfonamide as a white solid.5
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 120℃; for 3h;Inert atmosphere; A solution of 0.32 g (1.15 mmol) of 3-methanesulfonamido-2-methoxy-5-bromopyridine0.34 g (1.38 mmol) of diphenylolate borate,0.04 g (3.48 mmol) of potassium acetate and 0.06 g (0.08 mmol) of Pd (dppf) Cl2 in 100 mL eggplant vials,Adding dioxane 12mL, nitrogen protection, heating at 120 reflux 3h,To give the product containing 3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -5-methanesulfonamido-6-methoxypyridine Of the reaction system, cooled to room temperature,To this system was added (S) -N1- (6-bromo-2-benzothiazolyl) -1,2-tetrahydropyrrole dicarboxamide, 35 g (0.96 mmol) of potassium carbonate, 0.48 g (3.45 mmol) of potassium carbonate,Pd (dppf) Cl2 0.11 g (0.14 mmol) and water (3 mL), protected under nitrogen, heated at 120 C for 7 h,(V / V): chloroform / methanol = 25/1 to give 0.05 g of a white solid, yield: 10.83%, mp: 190-194, and the residue was purified by flash chromatography on silica gel. .

 

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