* 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.
Stage #1: With n-butyllithium In tetrahydrofuran; water at -78 - 20℃; for 0.166667 h; Inert atmosphere
Step 4Into a 300 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of l-(2-fluorophenoxy)-4-iodobenzene (3.3 g, 30.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at -78 °C. The resulting solution was stirred for 10 mins at -78°C and then tris(propan-2-yl)borate (2.1 g, 1 3.17 mmol, 1.06 equiv) was added dropwise with stirring at - 78 °C over 30 min. The resulting solution was stirred while the temperature warmed from -78 °C to room temperature. The reaction was then quenched by the addition of saturated aqueous NII4CI and concentrated under vacuum. The resulting solution was diluted with 30percent aquious potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37percent ). The resulting solution was extracted with ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2,2 g (90percent) of [4-(2-fSuorophenoxy)phenyl]boronic acid as a white solid
90%
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 0.166667 h; Inert atmosphere Stage #2: at -78 - 20℃; for 0.166667 h;
Step 4 Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of 1-(2-fluorophenoxy)-4-iodobenzene (3.3 g, 10.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at -78° C. The resulting solution was stirred for 10 mins at -78° C. and then tris(propan-2-yl)borate (2.1 g, 11.17 mmol, 1.06 equiv) was added dropwise with stirring at -78° C. over 10 min. The resulting solution was stirred while the temperature warmed from -78° C. to room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl and concentrated under vacuum. The resulting solution was diluted with 10percent aquious potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37percent). The resulting solution was extracted with ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2.2 g (90percent) of [4-(2-fluorophenoxy)phenyl]boronic acid as a white solid
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 0.166667 h; Inert atmosphere Stage #2: With Triisopropyl borate In tetrahydrofuran at -78 - 20℃; for 0.166667 h; Inert atmosphere Stage #3: With water; ammonium chloride In tetrahydrofuran
Step 4. Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of 1-(2-fluorophenoxy)-4-iodobenzene (3.3 g,10.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at -78 °C. The resulting solution was stirred for 10 mins at -78 °C and then tris(propan-2-yl)borate (2.1 g, 11.17 mmol, 1.06 equiv) was added dropwise with stirring at78 °C over 10 mm. The resulting solution was stirred while the temperature warmed from -78°C to room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl and concentrated under vacuum. The resulting solution was diluted with 10percent aqueous potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37percent ). The resulting solution was extracted with ethyl acetate andthe organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2.2 g (90percent) of [4-(2-fluorophenoxy)phenyl]boronic acid as a white solid.
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 1 h; Stage #2: at 20℃; for 6 h;
To a solution of I -(4-bromophenoxy)-2-lluoroben2ene (10 g, 37.4 mmoi), in tetrahydtx>furan (150 mL) at -78 "C was added n-batyllithium (2,5 M, 22.4 mL, 56,2 mmol) and th reaction mixture was stirred at that temperature- for 1 hour. Triisopropyl borate ( 10.3 g, 44,9 mmol) was then added and the reaction was allowed to warm up to room temperature with stirring for 6 hours. The reaction mixture was then quenched with a saturated .solution of ammonium chloride and concentrated under reduced pressure. The resultant residue was diluted with an aqueous solution of 3 percent KOH and neutral ized to pH 2-3 with dilute HQ. The resulting solution was extracted with ethyl acetate and the combined extracts were dried over anhydrous NiS(. filtered and evaporated in. vacuo to afford a crude compound which was purified by flash chromatography on silica gel ( 100-200 mesh) eluting with 40percent ethyl acetate in hexanes to afford the title compound as art off white solid i'2,6 g, 1 1 ' ). - NMR (CDt, 400 MHz) 6 8. 1 (d, / = S.6 Hz, 2H), 7.20 (m, 4H), 7.06 id, J = 8.6 Hz, 2H).
tert-butyl 3-[4-amino-3-[4-(2-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
59%
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃;Inert atmosphere;
Step 1Into a 100 mL, 3 -necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of tert-butyl 3-[4-amino-3-iodo-lH- pyrazolo[3,4-d]pyrimidin-l -yl]piperidine-l-carboxylate (300 mg, 0.68 mmol, 1.00 equiv) in dioxane/H20(7/3=V/V) (30 mL), <strong>[1402238-32-7][4-(2-fluorophenoxy)phenyl]boronic acid</strong> (500 mg, 2.16 mmol, 6.99 equiv), sodium carbonate (200 mg, 1 .89 mmoi, 0.26 equiv), and Pd(PPh3)4 (500 mg, 0.43 mmol, 3.19 equiv). The resulting solution was stirred overnight at 100 C in an oil bath an then concentrated under vacuum. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (100: 1) to give 0.2 g (59%) of tert-butyl 3-[4-ainino-3- [4-(2-fluorophenoxy)phenyl]-lH-pyrazolo[3,4-d]pyrimidin- l-yl]piperidme-l-carboxyIate as a light yellow solid.
Step 4Into a 300 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of l-(2-fluorophenoxy)-4-iodobenzene (3.3 g, 30.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at -78 C. The resulting solution was stirred for 10 mins at -78C and then tris(propan-2-yl)borate (2.1 g, 1 3.17 mmol, 1.06 equiv) was added dropwise with stirring at - 78 C over 30 min. The resulting solution was stirred while the temperature warmed from -78 C to room temperature. The reaction was then quenched by the addition of saturated aqueous NII4CI and concentrated under vacuum. The resulting solution was diluted with 30% aquious potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37% ). The resulting solution was extracted with ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2,2 g (90%) of [4-(2-fSuorophenoxy)phenyl]boronic acid as a white solid
90%
Step 4 Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of 1-(2-fluorophenoxy)-4-iodobenzene (3.3 g, 10.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at -78 C. The resulting solution was stirred for 10 mins at -78 C. and then tris(propan-2-yl)borate (2.1 g, 11.17 mmol, 1.06 equiv) was added dropwise with stirring at -78 C. over 10 min. The resulting solution was stirred while the temperature warmed from -78 C. to room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl and concentrated under vacuum. The resulting solution was diluted with 10% aquious potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37%). The resulting solution was extracted with ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2.2 g (90%) of [4-(2-fluorophenoxy)phenyl]boronic acid as a white solid
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃;Inert atmosphere;
Step Into a 100 mL, 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of text- butyl (3R)-3-[4-amino-3-iodo- 1 H- pyrazolo[3,4-d]pyrimidin~l~yijpiperidine-l -carboxylate (300 mg, 0.68 mmol, S .00 equiv) in dioxane/H20(7/3=V/V) (30 mL), <strong>[1402238-32-7][4-(2-fluorophenoxy)phenyl]boronic acid</strong> (500 mg, 2, 16 mmol, 6.99 equiv), sodium carbonate (200 mg, 1.89 mmol, 0.26 equiv), and Pd(PPh j)4 (500 mg, 0.43 mmol, 3.19 equiv), The resulting solution was stirred overnight at 100 C in an oil bath an then concentrated under vacuum. The residue was loaded onto a silica gel column and elated with dichloromethane/methanol (100: 1) to give 0.2 g (59%) of tert-butyl (3R)-3-[4- amino-3-[4-(2-fluorophenoxy)phenyl]-lH-pyrazolo[3,4-d]pyrirnidin-l-yl]piperidine-l- carboxylate as a light yellow solid.
59%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 100℃;
Into a 100 mL, 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of tert-butyl (3R)-3-[4-amino-3-iodo-1H-pyrazolo[3,4-d]pyriniidin-1-yl]piperidine-1-carhoxylate (300 tug, 0.68 mrnol, 1.00 equiv) in dioxane/H2O(7/3=VIV) (30 mL), <strong>[1402238-32-7][4-(2-fluorophenoxy)phenyl]boronic acid</strong> (500 mg, 2.16 inmol, 6.99 equiv), sodium carbonate (200 mg, 1.89 mmdl, 0.26 equiv), and Pd(PPh)4 (500mg, 0.43 mmol, 3.1.9 equiv). The resulting solution was stirred overnight at 100 C in an oil bath an then concentrated under vacuum. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (100:1) to give 0.2 g (59%) of teitbutyl (3R)-3-[4-amino-3-[4-(2-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrmidin-1-yl]piperidine-1-carboxylate as a light yellow solid.
59%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 100℃;Inert atmosphere;
Step 1 Into a 100 mL, 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of tert-butyl (3R)-3-[4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate (300 mg, 0.68 mmol, 1.00 equiv) in dioxane/H2O(7/3=V/V) (30 mL), <strong>[1402238-32-7][4-(2-fluorophenoxy)phenyl]boronic acid</strong> (500 mg, 2.16 mmol, 6.99 equiv), sodium carbonate (200 mg, 1.89 mmol, 0.26 equiv), and Pd(PPh3)4 (500 mg, 0.43 mmol, 3.19 equiv). The resulting solution was stirred overnight at 100 C. in an oil bath an then concentrated under vacuum. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (100:1) to give 0.2 g (59%) of tert-butyl (3R)-3-[4-amino-3-[4-(2-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate as a light yellow solid.
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 100℃;Inert atmosphere;
Step 1. Into a 100 mL, 3-necked round-bottom flask purged and maintained with an inertatmosphere of nitrogen, was placed a solution of tert-butyl (3R)-3-[4amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate (300 mg, 0.68 mmol, 1.00 equiv) in dioxane/H2O(7/3=V/V) (30 mL), <strong>[1402238-32-7][4-(2-fluorophenoxy)phenyl]boronic acid</strong> (500 mg, 2.16 mmol, 6.99 equiv), sodium carbonate (200 mg, 1.89 mmol, 0.26 equiv), and Pd(PPh3)4 (500 mg, 0.43 mmol, 3.19 equiv). The resulting solution was stirred overnight at 100 C in an oilbath an then concentrated under vacuum. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (100:1) to give 0.2 g (59%) of tert-butyl (3R)-3-[4-amino-3-[4-(2-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate as a light yellow solid.
tert-butyl (2S)-2-([4-amino-3-[4-(2-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
59%
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 1000℃;Inert atmosphere;
Step 5Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of tert-butyl (2R)-2-([4-amino-3-iodo- lH- pyrazolo[3,4-d]pyrirnidm- 3-yl]methyl)pyrfolidine-l -carboxylate (300 mg, 0.68 mmol, 1.00 equivj in dioxane H2Q(7/3=V/V) (30 mL), [4-(2-fluorophenoxy)phenyl]horonic acid (500 mg, 2.16 mmol, 3.19 equiv), sodium carbonate (500 mg, 4.72 mmol, 6.99 equiv), andPd(PP 3)4 (200 mg, 0.17 mmol, 0.26 equiv). The resulting solution was stirred overnight at 100 C in an oil bath and then concentrated under vacuum. The residue was loaded onto a silica gel column with dichloromethane/methanol (100:1 ) to give 0.2 g (59%) of tert-butyl (2S)-2-([4-ammo-3-[4-(2-fluorophenoxy)phenyl]- 1 H-pyrazolof3,4-d]pyrimidin- 1 -yljmethyl)- pyrrolidine- 1 -carboxylate as a 1 ight yellow solid.
59%
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 100℃;Inert atmosphere;
Step 5. Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of tert-butyl (2R)-2-([4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylate (300 mg, 0.68 mmol, 1.00 equiv) in dioxane/H2O(7/3=V/V) (30 mL), <strong>[1402238-32-7][4-(2-fluorophenoxy)phenyl]boronic acid</strong> (500 mg, 2.16 mmol, 3.19 equiv), sodium carbonate (500 mg, 4.72 mmol, 6.99 equiv), and Pd(PPh3)4 (200 mg, 0.17 mmol, 0.26 equiv). The resulting solution was stirred overnight at 100 C in an oil bath and then concentrated under vacuum. The residue was loaded onto a silica gel column with dichloromethane/methanol (100:1) to give 0.2 g (59%) of tert-butyl (2S)-2-([4-amino-3-[4-(2-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylate as a light yellow solid.
Step 4. Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of 1-(2-fluorophenoxy)-4-iodobenzene (3.3 g,10.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at -78 C. The resulting solution was stirred for 10 mins at -78 C and then tris(propan-2-yl)borate (2.1 g, 11.17 mmol, 1.06 equiv) was added dropwise with stirring at78 C over 10 mm. The resulting solution was stirred while the temperature warmed from -78C to room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl and concentrated under vacuum. The resulting solution was diluted with 10% aqueous potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37% ). The resulting solution was extracted with ethyl acetate andthe organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2.2 g (90%) of [4-(2-fluorophenoxy)phenyl]boronic acid as a white solid.
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; methanol; at 100℃;Inert atmosphere;
Step 5 Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of tert-butyl (2R)-2-([4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylate (300 mg, 0.68 mmol, 1.00 equiv) in dioxane/H2O(7/3=V/V) (30 mL), <strong>[1402238-32-7][4-(2-fluorophenoxy)phenyl]boronic acid</strong> (500 mg, 2.16 mmol, 3.19 equiv), sodium carbonate (500 mg, 4.72 mmol, 6.99 equiv), and Pd(PPh3)4 (200 mg, 0.17 mmol, 0.26 equiv). The resulting solution was stirred overnight at 100 C. in an oil bath and then concentrated under vacuum. The residue was loaded onto a silica gel column with dichloromethane/methanol (100:1) to give 0.2 g (59%) of tert-butyl (2S)-2-([4-amino-3-[4-(2-fluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)-pyrrolidine-1-carboxylate as a light yellow solid.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 85℃; for 3h;Inert atmosphere;
Step 109C[00322] A mixture of 109c (70 mg), 109d (114 mg), K2C03 (113 mg), and Pd(dppf)C12 (66 mg) in dioxanewater(5 ml0.5 ml) was stirred in under N2 at 85 C for 3 h. After cooled to room temperature, the solvents were removed. The residue was purified by silica gel chromatography to give 109e (100 mg). MS (ESI): mz=535 [M-f-H].
To a solution of I -(4-bromophenoxy)-2-lluoroben2ene (10 g, 37.4 mmoi), in tetrahydtx>furan (150 mL) at -78 "C was added n-batyllithium (2,5 M, 22.4 mL, 56,2 mmol) and th reaction mixture was stirred at that temperature- for 1 hour. Triisopropyl borate ( 10.3 g, 44,9 mmol) was then added and the reaction was allowed to warm up to room temperature with stirring for 6 hours. The reaction mixture was then quenched with a saturated .solution of ammonium chloride and concentrated under reduced pressure. The resultant residue was diluted with an aqueous solution of 3 % KOH and neutral ized to pH 2-3 with dilute HQ. The resulting solution was extracted with ethyl acetate and the combined extracts were dried over anhydrous NiS(. filtered and evaporated in. vacuo to afford a crude compound which was purified by flash chromatography on silica gel ( 100-200 mesh) eluting with 40% ethyl acetate in hexanes to afford the title compound as art off white solid i'2,6 g, 1 1 ' ). - NMR (CDt, 400 MHz) 6 8. 1 (d, / = S.6 Hz, 2H), 7.20 (m, 4H), 7.06 id, J = 8.6 Hz, 2H).
3-(4-(2-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
13.5%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium hydroxide; In N,N-dimethyl-formamide; at 120℃; for 16h;Inert atmosphere;
To a solution containing 3-iodo- f i/-pyxazoloP.4-< ]pyriMdi-4-amiae (3,0 g, I 1.5 romoi) and (4-(2-iliK>rophenoxy)phenyl)boronic acid in KN dimethylfonxutftode (20 mL) was added NaOH (900 mg, 22.9 trtmof). The reaction mixture was purged with nitrogen atmosphere and , {bisdfphciiyipiKLSphi o)ferrocciiepail diimi(Ii) dichloride (Pd(dppf)C 840 rag, 1 . 1 mmol) was slowly added at room temperature followed by beating at 1 0 C for 16 hours. The reaction mixture was cooled, filtered through eeiite and then poured info ice water and was extracted with ethyl acetate. The combined organic layer extracts were dried over anhydrous Na_SO* and ccmcenirated in vacuo to give a crude oil which was purified by column chromatography on silica gel (100-200 mesh), eiuting with 50% ethyl acetate: hexanes mixture to afford the title compound (500 rag, 13.5%) as a light brown solid. NMR ( DMS0-< 400 MHz): 5 13.55 (s, IH), 8.21 is, 1H), 7.? im, 2H), 7.66 (d, 8.6 Hz, 2H), 7.44 (m, H), 7.29 (m, 3H), 7, 12 (m, V 8.4 Hz, 2H).
(1R,3R)-3-{4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl}cyclohexyl acetate[ No CAS ]
(1R,3R)-3-(4-amino-3-(4-(2-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl acetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
69%
With tripotassium phosphate tribasic; tetrakis-(triphenylphosphine)-palladium In 1,4-dioxane; water monomer for 1.5h; Inert atmosphere; Reflux;
17.3 Step 3: (1R, 3R)-3-(4-amino-3-(4-(2-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl acetate
To a 25 mL two-necked-flask was added (1R, 3R)-3-(4-amino-3-iodo-1h-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexylacetate (0.50 g, 1.25 mmol), (4 - (2-fluorophenoxy) phenyl) boric acid (0.38 g, 1.62 mmol), potassium phosphate(0.79 g, 3.74 mmol), tetratriphenylphosphine palladium (0.29 g, 0.25 mmol), 20 mL of 1,4-dioxane and 10 mL of H2Ounder Ar. The mixture was heated to reflux for 1.5h. TLC showed that the reaction was completed. The reaction systemwas added with 15 mL H2O and extracted with DCM (10 mL33).The combined organic phase was washed with brine(20mL31) and then dried with anhydrous sodium sulfate. After filtration and concentration, the residue was purified withsilica gel column (DCM:methanol =100:1) to afford 390 mg product, yield 69%.MS ESI: m/z = 462, [M+H]+.
69%
With tripotassium phosphate tribasic; tetrakis-(triphenylphosphine)-palladium In 1,4-dioxane; water monomer for 1.5h; Inert atmosphere; Reflux;
17.3 Step 3: (1R, 3R)-3-(4-amino-3-(4-(2-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexyl acetate
To a 25 mL two-necked-flask was added (1R, 3R)-3-(4-amino-3-iodo-1h-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexylacetate (0.50 g, 1.25 mmol), (4 - (2-fluorophenoxy) phenyl) boric acid (0.38 g, 1.62 mmol), potassium phosphate(0.79 g, 3.74 mmol), tetratriphenylphosphine palladium (0.29 g, 0.25 mmol), 20 mL of 1,4-dioxane and 10 mL of H2Ounder Ar. The mixture was heated to reflux for 1.5h. TLC showed that the reaction was completed. The reaction systemwas added with 15 mL H2O and extracted with DCM (10 mL33).The combined organic phase was washed with brine(20mL31) and then dried with anhydrous sodium sulfate. After filtration and concentration, the residue was purified withsilica gel column (DCM:methanol =100:1) to afford 390 mg product, yield 69%.MS ESI: m/z = 462, [M+H]+.
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