硼酸酯合成

Copyright © 2013 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license. 1/6 2013-12-27 10:41:16 Query Query Results Date 1. Query HAR Cl HAR B O O 466 reactions in Reaxys 2013-12-27 10h:20m:03s (EST) Search as: As drawn, No salts, No mixtures Copyright © 2013 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license. 2/6 2013-12-27 10:41:16 HN Cl O O B B O O O O B NH Rx-ID: 8932380 View in Reaxys 1/8 Yield Conditions & References 80 % 28 :Under a nitrogen atmosphere, a reaction vessel of 20 ml in volume was charged with bis(pinacolate)diboron (0.50 g (2.0 mmol)), degassed methanol (7.2 g) and diisopropylethylamine (0.51 g (4.0 mmol)) and stirred at room temper- ature. The reaction vessel was charged with bis(l,5-cyclooctadiene)nickel (15 mg (0.05 mmol)), triphenylphosphine (28 mg (0.11 mmol)), and 4-chloroindole (0.20 g (1.32 mmol)) and stirred at 300C for 21 hours, and thereafter stirred at 500C for 3 hours. The reaction solution was analyzed by gas chromatography. As a result, 4-(4,4,5,5-tetramethyl- 1,3,2- dioxaborolan-2-yl)indole was contained in an amount of 0.26 g (1.05 mmol, yield:80percent). With N-ethyl-N,N-diisopropylamine, triphenylphosphine, bis(1,5-cyclooctadiene)nickel (0) in methanol, T= 20 - 50 °C , Inert atmosphere Patent; SUMITOMO CHEMICAL COMPANY, LIMITED; GENENTECH, INC.; MIKI, Takashi; SHIMASAKI, Yasu- haru; BABU, Srinivasan; CHENG, Zhigang; REYNOLDS, Mark, E.; TIAN, Qingping; WO2010/110782; (2010); (A1) English View in Reaxys 80 % 28 : 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indole Under a nitrogen atmosphere, a reaction vessel of 20 ml in volume was charged with bis(pinacolate)diboron (0.50 g (2.0 mmol)), degassed methanol (7.2 g) and diisopropylethylamine (0.51 g (4.0 mmol)) and stirred at room temperature. The reaction vessel was charged with bis(1,5-cyclooctadiene)nickel (15 mg (0.05 mmol)), triphenylphosphine (28 mg (0.11 mmol)), and 4-chloroindole (0.20 g (1.32 mmol)) and stirred at 30° C. for 21 hours, and thereafter stirred at 50° C. for 3 hours. The reaction solution was analyzed by gas chromatography. As a result, 4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)indole was contained in an amount of 0.26 g (1.05 mmol, yield: 80percent). With N-ethyl-N,N-diisopropylamine, triphenylphosphine, (1,5-cyclooctadiene)(cyclopentadienyl)nickel in methanol, Time= 24h, T= 20 - 50 °C , Inert atmosphere Patent; GENENTECH, INC.; SUMITOMO CHEMICAL COMPANY, LIMITED; US2012/123122; (2012); (A1) English View in Reaxys 72 % Chro- mat. With potassium acetate, bis(dibenzylideneacetone)-palladium(0), tri-cyclo-hexyl-phosphine in 1,4-dioxane, Time= 48h, T= 80 °C Ishida, Kousaku; Ishiyama, Tatsuo; Miyaura, Norio; Tetrahedron; vol. 57; nb. 49; (2001); p. 9813 - 9816 View in Reaxys Cl N O O B B O O O O B N Rx-ID: 8929544 View in Reaxys 2/8 Yield Conditions & References 82 % With potassium acetate, tris(dibenzylideneacetone)dipalladium (0) in 1,4-dioxane, Time= 5h, T= 110 °C Barder, Timothy E.; Billingsley, Kelvin L.; Buchwald, Stephen L.; Angewandte Chemie - International Edition; vol. 46; nb. 28; (2007); p. 5359 - 53631 View in Reaxys 41 % 27 :Under a nitrogen atmosphere, a reaction vessel of 20 ml in volume was charged with bis(pinacolate)diboron (1.34 g (5.3 mmol)), degassed methanol (7.2 g) and diisopropylethylamine (1.36 g (10.6 mmol)) and stirred at room temper- ature. The reaction vessel was charged with bis(l,5-cyclooctadiene)nickel (39 mg (0.14 mmol)), triphenylphosphine (74 mg (0.28 mmol)), and 3-chloropyridine (0.40 g (3.52 mmol)) and stirred at 300C for 21 hours, and thereafter stirred at500C for 3 hours. The reaction solution was analyzed by gas chromatography. As a result, 3-(4,4,5,5-tetramethyl-l, 3,2- dioxaborolan-2-yl)pyridine was contained in an amount of 0.29 g (1.42 mmol, yield: 41percent). Copyright © 2013 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license. 3/6 2013-12-27 10:41:16 With N-ethyl-N,N-diisopropylamine, triphenylphosphine, bis(1,5-cyclooctadiene)nickel (0) in methanol, T= 20 - 50 °C , Inert atmosphere Patent; SUMITOMO CHEMICAL COMPANY, LIMITED; GENENTECH, INC.; MIKI, Takashi; SHIMASAKI, Yasu- haru; BABU, Srinivasan; CHENG, Zhigang; REYNOLDS, Mark, E.; TIAN, Qingping; WO2010/110782; (2010); (A1) English View in Reaxys 41 % 27 : 3-(4,4,5,5-tetramethyl-1,2-dioxaborolan-2-yl)pyridine Under a nitrogen atmosphere, a reaction vessel of 20 ml in volume was charged with bis(pinacolate)diboron (1.34 g (5.3 mmol)), degassed methanol (7.2 g) and diisopropylethylamine (1.36 g (10.6 mmol)) and stirred at room tempera- ture. The reaction vessel was charged with bis(1,5-cyclooctadiene)nickel (39 mg (0.14 mmol)), triphenylphosphine (74 mg (0.28 mmol)), and 3-chloropyridine (0.40 g (3.52 mmol)) and stirred at 30° C. for 21 hours, and thereafter stirred at 50° C. for 3 hours. The reaction solution was analyzed by gas chromatography. As a result, 3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)pyridine was contained in an amount of 0.29 g (1.42 mmol, yield: 41percent). With N-ethyl-N,N-diisopropylamine, triphenylphosphine, (1,5-cyclooctadiene)(cyclopentadienyl)nickel in methanol, Time= 24h, T= 20 - 50 °C , Inert atmosphere Patent; GENENTECH, INC.; SUMITOMO CHEMICAL COMPANY, LIMITED; US2012/123122; (2012); (A1) English View in Reaxys 82 % Chro- mat. With potassium acetate, bis(dibenzylideneacetone)-palladium(0), tri-cyclo-hexyl-phosphine in 1,4-dioxane, Time= 48h, T= 80 °C Ishida, Kousaku; Ishiyama, Tatsuo; Miyaura, Norio; Tetrahedron; vol. 57; nb. 49; (2001); p. 9813 - 9816 View in Reaxys O O B B O O N O N Cl O O B N N O Rx-ID: 10707319 View in Reaxys 3/8 Yield Conditions & References 100 % 92 :A mixture of 2-chloro-6-methoxypyrazine (0.50 g, 3.46 mmol), bis(pinacolato)diboron (0.966 g, 3.80 mmol), tris(di- benzylideneacetone)dipalladium(0) (0.095 g, 0.10 mmol), tricyclohexyl phosphine (0.116 g, 0.42 mmol) and potassium acetate (0.509 g, 5.19 mmol) in 1,2-dimethoxyethane (10 mL) was run for 3 h at 150° C. in a microwave oven under argon atmosphere. The reaction mixture was partitioned between water and diethyl ether and the organic phases were pooled, dried over magnesium sulfate, filtered and concentrated to give 1.15 g (quantative yield) of the crude title compound which was used in the next reaction step without further purification. MS (CI) m/z 237. With water, potassium acetate, tris-(dibenzylideneacetone)dipalladium(0), tri-cyclo-hexyl-phosphine in ethylene glycol dimethyl ether, Time= 3h, T= 150 °C Patent; AstraZeneca AB; Astex Therapeutics Ltd.; US2007/299087; (2007); (A1) English View in Reaxys 100 % 90 :Example 90 2-Methoxy-6-('4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl')pyrazine-; A mixture of 2-chloro-6-methox- ypyrazine (0.50 g, 3.46 mmol), bis(pinacolato)diboron (0.966 g, 3.80 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.095 g, 0.10 mmol), tricyclohexyl phosphine (0.116 g, 0.42 mmol) and potassium acetate (0.509 g, 5.19 mmol) in 1,2- dimethoxy ethane (10 mL) was run for 3h at 15O0C in a microwave oven under argon atmosphere. The reaction mixture was partitioned between water and diethyl ether and the organic phases were pooled, dried over magnesium sulfate, filtered and concentrated to give 1.15 g (quantative yield) of the crude title compound which was used in the next reaction step without further purification; MS (CI) m/z 237. With potassium acetate, tris-(dibenzylideneacetone)dipalladium(0), tri-cyclo-hexyl-phosphine in ethylene glycol di- methyl ether, Time= 3h, T= 150 °C , Microwave irradiation Patent; ASTRAZENECA AB; ASTEX THERAPEUTICS LTD; WO2007/145571; (2007); (A1) English View in Reaxys Copyright © 2013 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license. 4/6 2013-12-27 10:41:16 600 mg 137 :Example 137 _;A mixture of 2-chloro-6-methoxypyrazine (500 mg, 3.46 mmol, 1.0 eq), bis(pinacolato)diboron (1.05 g, 4.13 mmol, 1.2 eq), Pd2(dba)3 (95 mg, 0.1 mmol, 0.029 eq), P(Cy)3 (120 mg, 0.43 mmol, 0.13 eq), and potassium acetate (600 mg, 6.11 mmol, 1.77 eq) in 1,2-dimethoxyethane (10 mL) was irradiated under argon at 150° C. in a microwave oven for 3 h. _;The mixture was allowed to cool to RT, quenched with water and extracted with ethyl acetate. _;The combined organic layers were washed with brine, dried over Na2SO4 and filtered. _;The filtrate was concentrated in vacuo to afford the pinacol ester (600 mg). With tris-(dibenzylideneacetone)dipalladium(0), potassium acetate, tri-cyclo-hexyl-phosphine in ethylene glycol di- methyl ether, Time= 3h, T= 150 °C , Inert atmosphere, Microwave irradiation Patent; INTELLKINE, LLC; INFINITY PHARMACEUTICALS, INC.; CASTRO, Alfredo C.; EVANS, Catherine A.; JANARDANANNAIR, Somarajannair; LESCARBEAU, Andre; LIU, Tao; SNYDER, Daniel A.; TREMBLAY, Martin R.; REN, Pingda; LIU, Yi; LI, Liansheng; CHAN, Katrina; US2013/53362; (2013); (A1) English View in Reaxys O O B B O O N HN Cl O O B N HN Rx-ID: 28029512 View in Reaxys 4/8 Yield Conditions & References 94 % 4-chloro-1 H-pyrrolo[2,3-b]pyridine (457mg, 3mmol), palladium acetate (13.2mg, 2percent), 2-(dicyclohexylphosphi- no)biphenyl (42mg, 4percent), bis(pinacolato) diborane (1.5g, 6mmol) and potassium acetate (590mg, 6mmol) were taken up in a degassed dioxane (1OmL) under an atmosphere of nitrogen. The resulting mixture was stirred at 1001C for 5 hours, cooled to room te mperature and filtered through a thin pad of Celite (eluting with ethyl acetate). The eluent was washed with water, brine, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was purified by flash chromatography to give the product (690mg) with a yield of 94percent. With potassium acetate, palladium diacetate, 2-dicyclohexylphosphino-1,1'-biphenyl in 1,4-dioxane, Time= 5h, T= 100 °C Patent; S BIO PTE LTD; WO2009/93981; (2009); (A1) English View in Reaxys 48 % M.M-18.b :Step b - 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 l-l-pyrrolo[2,3-b]pyridine; A solution of 2-(dicy- clohexylphosphino)biphenyl (0.287g, 0.819mmol), 6/s(pinacolato)diboron (0.915g, 3.60mmol), Acetic acid potassium salt (0.965g, 9.83mmol), fr7s(dibenzylideneacetone)dipalladium(0) (0.03Og, 0.032mmol) and 4-chloro- 1 H-pyrrolo[2,3- b]pyridine (0.50Og, 3.28mmol) in dioxane (10ml) was degassed, placed under a nitrogen atmosphere and heated under reflux for 3 hours. The solvent was removed in vacuo. The residue was taken up in MeOH and loaded onto a MP-TsOH cartridge (2500mg). The cartridge was washed with MeOH then with 2M ammonia in MeOH and the solvent reduced in vacuo to afford 4-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)-1 H-pyrrolo[2,3-b]pyridine (0.394g, 1.62mmol, 48percent) of a brown solid. LCMS (2) Rt: 1.39min; m/z (ES+) 245. With potassium acetate, tris-(dibenzylideneacetone)dipalladium(0) in 1,4-dioxane, Time= 3h, Heating / reflux Patent; SAREUM LIMITED; WO2008/139161; (2008); (A1) English View in Reaxys 48 % 91.1 :To a suspension of 4-chloro-lH-pyrrolo [2, 3-b] pyridine (1.00 g, 6.55 mraol), 4, 4,4' , 4' , 5,5, 5' , 5' -octamethyl-2,2' -bi- 1,3,2-dioxaborolane (2.16 g, 8.52 iranol) , biphenyl-2- yl (dicyclohexyl)phosphane (575 mg, 1.64 iranol) and po- tassium acetate (2.25 g, 22.9 iranol) in 1,2-dimethoxyethane (20 mL) was added tris (dibenzylideneacetone)dipalladi- um(O) (600 mg, 0.655 iranol). The mixture was degassed and stirred at 900C for 5 h under argon atmosphere. To the resulting mixture were added EtOAc (100 mL) and water (50 mL) . An insoluble material was removed by filtration and the layers of the filtrate were separated. The aqueous layer was extracted with EtOAc (10 mL) . The combined organic layers were washed with brine (10 mL) , dried over Na2SO4 and concentrated under reduced pressure. The residue was triturated with EtOAc/hexane (1:1, 10 mL) to give pale yellow solid (442 mg, 28percent) . The filtrate was concen- trated under reduced pressure, and the residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/ EtOAc to 60:40 hexane/EtOAc) to give the title compound (320 mg, 20percent, total yield = 762 mg, 48percent) as a colorless solid: 1H NMR (300 MHz, DMSO-d6) 1.35 (12H, s), 6.66 (IH, dd, J = 3.2, 1.9 Hz), 7.28 (IH, d, J = 4.5 Hz), 7.51 (IH, t, J = 3.2 Hz), 8.21 (IH, d, J = 4.5 Hz), 11.63 (IH, br s) . Copyright © 2013 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license. 5/6 2013-12-27 10:41:16 With potassium acetate, 2-dicyclohexylphosphino-1,1'-biphenyl, tris-(dibenzylideneacetone)dipalladium(0) in ethylene glycol dimethyl ether, Time= 5h, T= 90 °C , Inert atmosphere Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; OGURO, Yuya; KURASAWA, Osamu; WO2010/101302; (2010); (A1) English View in Reaxys S N Cl HO OH B O O O O O B S N Cl Rx-ID: 31695213 View in Reaxys 5/8 Yield Conditions & References 82 % 141.1 :Step 1 Diisopropylamine (0.66 mL, 4.6 mmol) and triisopropylborate (1.26 mL, 5.44 mmol) were dissolved in 52 mL of anhy- drous diethyl ether and then cooled to -90° C. n-Butyllithium (2.6 M in toluene, 1.77 mL, 4.6 mmol) was added slowly to the reaction and the mixture was stirred for 30 min. 2-Chlorothiazole (0.5 g, 4.18 mmol) was added and the reaction was allowed to gradually reach room temperature over 3 h. A solution of pinacol (0.69 g, 5.85 mmol) in 5 mL of diethyl ether was added. After 15 min, acetic acid (0.26 mL, 4.6 mmol) was added and the mixture was then filtered through Celite, rinsing with more diethyl ether. The filtrate was evaporated and the residue was distilled using a Kugelrohr apparatus at a temperature of 120-130° C. to give 0.84 g (82percent) of 2-chloro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiazole. Stage 1: With n-butyllithium, diisopropylamine in diethyl ether, toluene, Time= 3h, T= -90 - 20 °C Stage 2: in diethyl ether, toluene, Time= 0.25h, T= 20 °C Stage 3: With acetic acid in diethyl ether, toluene Patent; Hendricks, Robert Than; Hermann, Johannes; Kondru, Rama; Lou, Yan; Lynch, Stephen M.; Owens, Timothy D.; Soth, Michael; US2011/230462; (2011); (A1) English View in Reaxys N Cl Cl N O O B B O O O O B N N Cl Rx-ID: 30476470 View in Reaxys 6/8 Yield Conditions & References A mixture of tris(dibenzylideneacetone)dipalladium(0) (0.275 g, 0.300 mmol) and tricyclohexylphosphine (0.202 g, 0.720 mmol) in dioxane (50 mL) under argon was stirred for 30 min at room temperature. 2,6-Dichloropyrazine, bis(pi- nacolato)diboron (2.79 g, 11.00 mmol) and potassium acetate (1.472 g, 15.00 mmol) were added and the mixture was stirred at 80 °C for 18 hrs. The mixture was cooled to room temperature and filtered through a thin layer of celites. The filtrate was concentrated under reduced pressureand providing crude 2-chloro-6-(4,4,5,5-tetramethyl-l,3,2-dioxaboro- lan-2- yl)pyrazine, which was directly used in the next step without purification. LCMS (m/z): 158.9 [boronic acid frag- ment+H]+; Rt = 0.33 min. With potassium acetate, tri-cyclo-hexyl-phosphine, tris-(dibenzylideneacetone)dipalladium(0) in 1,4-dioxane, Time= 18h, T= 80 °C , Inert atmosphere Patent; NOVARTIS AG; BARSANTI, Paul A.; HU, Cheng; PFISTER, Keith B.; SENDZIK, Martin; SUTTON, James; WO2011/26904; (2011); (A1) English View in Reaxys 1 :A mixture of tris(dibenzylideneacetone)dipalladium(0) (0.275 g, 0.300 mmol) and tricyclohexylphosphine (0.202 g, 0.720 mmol) in dioxane (50 mL) under argon was stirred for 30 min at room temperature. 2,6-Dichloropyrazine, bis(pi- nacolato)diboron (2.79 g, 1 1 .00 mmol) and potassium acetate (1 .472 g, 15.00 mmol) were added and the mixture was stirred at 80 °C for 18 hrs. The mixture was cooled to room temperature and filtered through a thin layer of celites. The filtrate was concentrated under reduced pressureand providing crude 2-chloro-6-(4,4,5,5-tetramethyl-1 ,3,2-diox- Copyright © 2013 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license. 6/6 2013-12-27 10:41:16 aborolan-2-yl)pyrazine, which was directly used in the next step without purification. LCMS (m/z): 158.9 [boronic acid fragment+H]+; Rt = 0.33 min. With potassium acetate, tri-cyclo-hexyl-phosphine, tris-(dibenzylideneacetone)dipalladium(0) in 1,4-dioxane, Time= 18h, T= 80 °C , Inert atmosphere Patent; NOVARTIS AG; BARSANTI, Paul, A.; HU, Cheng; JIN, Xianming; NG, Simon, C.; PFISTER, Keith, B.; SENDZIK, Martin; SUTTON, James; WO2012/101064; (2012); (A1) English View in Reaxys N N N Cl O O B B O O O O B N N N Rx-ID: 33426642 View in Reaxys 7/8 Yield Conditions & References 2.2b :(2b) 5-[2-(4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl))pyridyl]pyrimidineA 25 mL 3-neck round-bottomed flask equipped with condenser, thermometer and nitrogen bubbler was charged with 1 ,4-dioxane (10 mL). The solvent was sparged with N2 for 30 minutes and potassium acetate (1 .47 g, 15.0 mmol), 5-(4-chloro-2-pyridyl)pyrimidine from step (2a) (0.96 g, 5.00 mmol), bis(pinacolato)diboron (1 .52 g, 6.00 mmol),tris(dibenzylideneacetone)dipalladium(0) (0.09 g, 0.10 mmol) and 2- dicyclohexylphosphino-2',4',6'-triisopropyl-1 ,1 '-biphenyl (0.19 g, 0.40 mmol) were added and the reaction mixture was heated to reflux (T, = 75 °C). The reaction was allowed to cool to room temperature and was filtered and rinsed with ethyl acetate (100 ml_). The eluent wasconcentrated to a deep brown solid (1 .92 g, crude) that was used directly for the next reaction step without further purification With potassium acetate, tris-(dibenzylideneacetone)dipalladium(0), 2-(2,4,6-i-Pr3 C6H2)-C6H4-PCy2 in 1,4-dioxane, T= 75 °C , Inert atmosphere Patent; E. I. DU PONT DE NEMOURS AND COMPANY; FENNIMORE, Adam; HOWARD, Michael, Henry, Jr.; WO2012/88192; (2012); (A1) English0.7 View in Reaxys S N Cl HO OH O O B S N Cl Rx-ID: 10184002 View in Reaxys 8/8 Yield Conditions & References 86 % Stage 1: With tri-isopropoxy-borane, lithium diisopropyl amide in diethyl ether, T= -90 - 20 °C Stage 2: in diethyl ether, Time= 0.25h, T= 20 °C Mihovilovic, Marko D.; Schnuerch, Michael; Stanetty, Peter; Journal of Organic Chemistry; vol. 71; nb. 10; (2006); p. 3754 - 37611 View in Reaxys