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CAS No. : | 942920-55-0 | MDL No. : | MFCD11518924 |
Formula : | C10H9BrN2O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | VLZWUULVFAASBC-UHFFFAOYSA-N |
M.W : | 269.10 | Pubchem ID : | 44608107 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-H335 | 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 |
---|---|---|
68% | With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 90℃; for 48h; | A mixture of <strong>[942920-55-0]ethyl 4-bromo-1H-pyrrolo[2,3-b]pyridine-2-carboxylate</strong> (1.0 g, 3.9 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (2.1 g, 7.8 mmol), KOAc (1.2 g, 11.7 mmol) and Pd(dppf)Cl2 (0.3 g, 0.4 mmol) in DMF (20 mL) was heated at 90 C. for 48 h under inert atmosphere. After cooling to rt, the reaction was quenched by aqueous NH4Cl. The resulting mixture was extracted with AcOEt. The organic layer was washed with brine, water, and dried over sodium sulfate. Concentration in vacuo gave the residue, which was purified by YAMAZEN Fast Flow Liquid Chromatography (silica gel, EtOAc:hexane=1:1) to give the desired product as a white solid (0.8 g, 68%). 1H NMR (400 MHz, DMSO-d6) ppm 1.33-1.37 (m, 15H), 4.37 (q, 2H, J=7.1 Hz), 7.29 (d, 1H, J=2.0 Hz), 7.40 (d, 1H, J=4.5 Hz), 8.44 (d, 1H, J=4.3 Hz), 12.55 (brs, 1H). MS (ESI): m/z 315 (M-1)-, 317 (M+1)+ |
68% | With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 90℃; for 48h; | Ethyl 4-bromo-1 H-pyrrolo[2,3-6]pyridine-2-carboxylate (1.0 g, 3.9 mmol), 4l4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (2.1 g, 7.8 mmol), KOAc (1.2 g, 11.7 mmol) and Pd(dppf)CI2 (0.3 g, 0.4 mmol) in DMF (20 ml_) was heated at 90 0C for 48 h under inert atmosphere. After cooling to rt, the reaction was quenched with aqueous NH4CI. The resulting mixture was extracted with AcOEt. The organic layer was washed by water, brine, and dried over sodium sulfate. Concentration in vacuo gave the residue, which was purified by YAMAZEN Fast Flow Liquid Chromatography (silica gel, EtOAc.hexane , 1:1) to give the desired product as a white solid (0.8 g, 68 %). 1H NMR (400MHz, DMSO-d6) ppm 1.33- <n="98"/>1.37 (m, 15H), 4.37 (q, 2H, J = 7.1 Hz), 7.29 (d, 1 H1 J = 2.0 Hz), 7.40 (d, 1 H1 J = 4.5 Hz), 8.44 (d, 1 H, J = 4.3 Hz), 12.55 (brs, 1 H). LC/MS: m/z 315 (M-1 )-, 317 (M+1)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | Step A: Ethyl 4-bromo-1 H-pyrrolor2,3-lpyridine-2-carboxylate; Ethyl 1 H-pyrrolo[2,3-]pyridine-2-carboxylate-7-oxide (1 g, 5 mmol), (prepared using methods disclosed in WO 2000/044753 see Example 6, Step C), was added to a suspension of tetramethylammonium bromide (1.2 g, 7.5 mmol) in N, N- dimethylformamide (50 ml_). The resulting mixture was cooled to 0 C and methanesulfonic anhydride (1.7 g, 10 mmol) was added portionwise. After being warmed up to room temperature and stirred for another 6 hours, the reaction mixture was poured into water (100 ml_). After neutralization with 50 % aqueous sodium hydroxide, the resulting solution was extracted with ethyl acetate, followed by washing the organic layer with brine and water. Concentration in vacuo gave the residue, which underwent SCX purification to afford the title compound as a pale yellow solid (1 g, 77 %). 1H NMR (400 MHz, DMSO-d6) ppm 1.35 (t, 3 H, J = 7.1 Hz), 4.36 (q, 2 H1 J = 7.1 Hz), 7.05 (d, 1 H, J = 2.0 Hz), 7.48 (d, 1 H1 J = 5.1 Hz), 8.28 (d, 1 H, J = 5.1 Hz), 12.95 (brs, 1 H). | |
77% | With tetramethylammonium bromide; Methanesulfonic anhydride; In N,N-dimethyl-formamide; at 0 - 20℃; for 6h; | Ethyl 1H-pyrrolo[2,3-b]pyridine-2-carboxylate 7-oxide (1.0 g, 5.0 mmol), which was prepared according to WO2000044753, was added to a suspension of tetramethylammonium bromide (1.2 g, 7.5 mmol) in DMF (50 mL). The resulting mixture was cooled to 0 C. and methanesulfonic anhydride (1.7 g, 10 mmol) was added portion wise. After being warmed up to rt and stirred for another 6 h, the reaction mixture was poured into water (100 mL). By neutralizing it with 50% aqueous sodium hydroxide, the resulting solution was extracted with AcOEt, followed by washing the organic layer with brine and water. Concentration in vacuo gave the residue, which underwent SCX purification to afford the desired compound as a pale yellow solid (1.0 g, 77%). 1H NMR (400 MHz, DMSO-d6) ppm 1.35 (t, 3H, J=7.1 Hz), 4.36 (q, 2H, J=7.1 Hz), 7.05 (d, 1H, J=2.0 Hz), 7.48 (d, 1H, J=5.1 Hz), 8.28 (d, 1H, J=5.1 Hz), 12.95 (brs, 1H). MS (ESI): m/z 269, 271 (M+1)+ |
77% | With tetrabutylammomium bromide; Methanesulfonic anhydride; In N,N-dimethyl-formamide; at 0 - 20℃; for 6h; | Ethyl 1H-pyrrolo[2,3-6]pyridine-2-carboxylate 7-oxide (1.0 g, 5.0 mmol), which was prepared according to WO2000044753, and tetramethylammonium bromide (1.2 g, 7.5 mmol) were added to DMF (50 iml_). The mixture was cooled to 0 0C and methanesulfonic anhydride (1.7 g, 10 mmol) was added portion wise. The resulting suspension was warmed up to rt and stirred for 6 h. The mixture was poured in water (100 ml_) and the solution was neutralized with 50 % aqueous NaOH. The resulting solution was extracted with AcOEt, and then, the organic layer was washed by water and brine. Concentration in vacuo gave the residue, which was purified by SCX cartridge to afford the desired compound as a pale yellow solid (1.0 g, 77%). 1H NMR (400MHz, DMSO-c/6) ppm 1.35 (t, 3H1 J = 7.1 Hz), 4.36 (q, 2H, J = 7.1 Hz), 7.05 (d, 1 H, J = 2.0 Hz), 7.48 (d, 1 H1 J = 5.1 Hz), 8.28 (d, 1 H, J = 5.1 Hz), 12.95 (brs, 1 H). LC/MS: m/z 269, 271 (M+1)+ |
61% | With tetramethylammonium bromide; Methanesulfonic anhydride; In chloroform; at 0 - 25℃; for 16h; | To a stirred solution of 2-(ethoxycarbonyl)-lH-pynOlo[2,3-b]pyridine 7-oxide (3.50 g, 17.0 mmol) and Me4NBr (3.92 g, 25.5 mmol) in CHCb (40 mL) at 0 C was added Ms20 (5.91 g, 34.0 mmol) in portions. The reaction mixture was allowed to warm to 25 C and stir for 16 h. A pale yellow suspension was formed. LCMS showed the reaction was completed. The mixture was concentrated under reduced pressure to give a residue. The residue and the above batch were combined and neutralized with cold 0.5 N aq NaHCCb (80 mL) and stirred for 0.5 hour and then filtered. The filter cake was further purified by washing with EtOAc/pentane (15 mL/30 mL) to give ethyl 4-bromo-lH-pynOlo[2,3-b]pyridine-2- carboxylate (3.2 g, average yield: 61%) as an off-white solid. NMR (400 MHz, DMSO-rfc) d 1.36 (3H, t, J= 7.2 Hz), 4.37 (2H, q, J= 12 Hz), 7.06 (1H, s), 7.48 (1H, d, J= 5.2 Hz), 8.29 (1H, d, J= 4.8 Hz), 12.96 (1H, br s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium tert-butylate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In N,N-dimethyl-formamide; at 120℃; for 0.5h;Microwave irradiation; | Step B: Ethyl 4-[(4-nitrophenyl)aminol-1/-/-pyrrolof2,3-ipyridine-2-carboxylate; To a suspention of ethyl 4-bromo-1 /-/-pyrrolo[2,3-]pyridine-2-carboxylate (Step A) (538.2 mg, 2 mmol), potassium tert-butoxide (448.8 mg, 4 mmol), 4-nitroaniline (commercially available, for example, from Sigma-Aldrich) (828.8 mg, 6 mmol), and EPO <DP n="56"/>lambda/,lambda/-dimethylformamide (18 ml_) in a microwave vial was added Pd(dppf)CI2 (326.6 mg, 0.4 mmol). After capping, the mixture was heated with Creator at 120 0C for 30 min. The reaction mixture was quenched by saturated aqueous ammonium chloride, and extracted with dichloromethane (20 ml_, 3 times). The organic layer was washed with brine, dried over sodium sulfate, and then evaporated to dryness under reduced pressure. The residue was used for the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 120℃; for 0.5h;Microwave irradiation; | Ethyl 4-bromo-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (step A in general intermediate 8, 134.6 mg, 0.5 mmol) and 1-ethyl-3-(3-nitrophenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (general intermediate 9, 171.5 mg, 0.5 mmol) were dissolved in DME (4 mL) and aqueous Na2CO3 (2 M, 0.5 mL). The resulting solution and Pd(PPh3)4 (34.7 mg, 0.03 mmol) were added to a microwave vial. After capping, the mixture was heated with Creator at 120 C. for 30 minutes. SCX purification afforded the residue, which was directly used for the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
500 mg | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 140℃; for 1h; | To a mixture ethyl 4-bromo-1 H-pyrrolo[2,3-b]pyridine-2-carboxylate (500 mgs, 1.86 mmol) and 2-((tetrahydro-2H-pyran-4-yl)oxy)-5-(4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)benzonitrile (673 mgs, 2.0 mmol) in DME (6 mL) was 2.0 M aqueous Na2CO3 (2.0 mL, 4 mmol) and Pd(PPh3)4 (107 mgs, 0.09 mmol). The reaction mixture was heated at 140 C for 1 hr. After cooling to rt, ethyl acetate (10 mL) and water (20 mL) was added and the solids were filtered and washed with water and dried to give ethyl 4-(3-cyano-4-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)-1 H-pyrrolo[2,3- b]pyridine-2-carboxylate (500 mgs) LCMS-ESI+ (m/z): [M+H]+ calcd for C22H21 N3O4 as (M+H)+ 392.4 found: 392.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36.1% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 90℃; for 16h;Inert atmosphere; | A solution of 2'-(bis(4-methoxybenzyl)amino)-N,N-dimethyl-5'-(4, 4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)-[2,3'-bipyridine]-5-carboxamide (3.00 g, 4.93 mmol) in dioxane (15 mL) and H2O (5 mL) was added ethyl 4-bromo-lH-pyrrolo[2,3-b]pyridine-2- carboxylate (1.00 g, 3.72 mmol), Pd(dppf)Cl2 (0.271 g, 0.371 mmol) and Na2C03 (1.18 g, 11.2 mmol). The mixture was stirred at 90 C under N2 atmosphere for 16 h. A black suspension was formed. LCMS showed the purity of desired product (Rt = 0.709 min; MS Calc?d: 670.8; MS Found: 671.3 [M+H]+). The mixture was added sat.NFUCl (40 mL), extracted with EtOAc (40 mL x3). The combined layer was washed with brine (30 mL), dried over Na2SCri and concentrate. The residue was purified by Combi Flash (EtOAc in PE from 0 to 100%) to give ethyl 4-(2'-(bis(4-methoxybenzyl)amino)-5-(dimethylcarbamoyl)-[2,3'-bipyridin]-5'-yl)-lH- pyrrolo[2,3-b]pyridine-2-carboxylate (0.9 g, yield: 36.1%) as a brown solid. NMR (400 MHz, CDCb) d 1.44 (3H, t, J= 7.2 Hz), 3.03 (3H, s), 3.15 (3H, s), 3.80 (6H, s), 4.15 (4H, s), 4.46 (2H, q, J= 7.2 Hz), 6.83 (4H, d , J= 8.4 Hz), 7.06 (4H, d, J= 8.4 Hz), 7.28 (1H, d, J= 4.8 Hz), 7.47 (1H, s), 7.75-7.81 (2H, m), 8.21 (1H, d , J= 2.4 Hz), 8.55 (1H, d , J= 4.8 Hz), 8.75- 8.78 (2H, m), 10.13 (1H, br s). |
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