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CAS No. : | 640735-25-7 | MDL No. : | MFCD11616419 |
Formula : | C16H25FN2Si | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | YESANHMKGXGZLQ-UHFFFAOYSA-N |
M.W : | 292.47 | Pubchem ID : | 11266334 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 | UN#: | |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | |
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 |
---|---|---|
94% | With tetrabutyl ammonium fluoride In tetrahydrofuran at 0 - 20℃; for 1 h; Inert atmosphere | [0722] To a stirred solution of 4-fluoro-i-(triisopropylsilyl)-1H-pyrrolo [2,3-bj pyridine (3 g, 10 mmol) in THF (15 mL) at 0 °C under an argon atmosphere was added tetra butyl ammonium fluoride 1M in THF (10.5 mL). The reaction mixture was warmed to room temperature and stirred for 1 h. After consumption of starting material (by TLC), the reactionmixture was diluted with water (50 mL) and extracted with EtOAc (2 x 100 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by column chromatography using 20percentEtOAc: Hexane to afford 4-fluoro-1H-pyrrolo [2,3-bj pyridine (1.3 g, 94percent) as an off-white solid. ‘H NMR (CDC13, 400 MHz): 10.52 (brs, 1H), 8.30-8.25 (m, 1H), 7.32-7.30 (m, 1H), 6.81 (dd, 1H), 6.59 (s, 1H); TLC: 20percent EtOAc Hexane (R 0.2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: methyl chloroformate In tetrahydrofuran; cyclohexane at -78℃; for 0.416667h; Further stages.; | |
46% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 1h; Inert atmosphere; Stage #2: methyl chloroformate In tetrahydrofuran; cyclohexane at -78℃; for 1.25h; | 18.1 Methyl 4-fluoro-1-triisopropylsilylpyrrolo[2,3-b]pyridine-5-carboxylate (P18-1a) To a solution of 4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (5.93 g, 20.31 mmol) in distilled tetrahydrofuran (120 mL) was added sec-butyllithium (1.4 M in cyclohexane, 32 mL, 44.8 mmol) dropwise at -78 °C over 30 min under argon. The mixture was stirred at -78 °C for 30 min. To the mixture was added a solution of methyl chloroformate (4.7 mL, 60.7 mmol) in distilled tetrahydrofuran (50 mL) dropwise at -78 °C over 45 min. The reaction mixture was stirred at -78 °C for 30 min. The reaction was quenched with saturated aqueous ammonium chloride (120 mL) and the mixture was extracted with n-heptane (2 x 120 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated. The residue was purified by gradient silica gel column chromatography eluting with n-heptane:ethyl acetate (100:0 to 95:5) to afford the title compound (3.26 g, 9.30 mmol, 46%) as a pale yellow oil.LCMS Method A: 81%, tR=2.183 min, m/z = 351.2 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.7% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 1h; Stage #2: With carbon tetrabromide In tetrahydrofuran; cyclohexane at -78℃; for 1h; | 6.3 Step 3: Preparation of 5-Bromo-4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine (833.0 mg, 2.85mmol)in THF (34 mL) at -78 °C was treated drop wise with sec-butyllithium solution,1.4M in cyclohexane (4.48 mL, 6.27 mmol). The reaction was stirred at -78 °Cfor 1 hour. A solution of carbon tetrabromide (2.36g, 7.l2mmol) in THF (6.3mL)was added drop wise and the reaction was stirred at -78 °C for a further 1 hour.The reaction was quenched by the addition of saturated aqueous ammonium chloride. The mixture was extracted with iso-hexane (x2) and the combined extracts washed with saturated aqueous sodium chloride. The solution was dried over anhydrous Mg504 and concentrated to a brown oil. The crude material waspurified by automated column chromatography, eluting with isohexane. Fractions found to contain pure product were combined and solvent removed in vacuo to afford the desired compound as a yellow gum that solidified on standing, 0.97g, 91.7%. |
91.7% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 1h; Stage #2: With carbon tetrabromide In tetrahydrofuran; cyclohexane at -78℃; for 1h; | 6.3 Step 3: Preparation of 5-Bromo-4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine (833.0 mg, 2.85 mmol) in THF (34 mL) at -78° C. was treated drop wise with sec-butyllithium solution, 1.4M in cyclohexane (4.48 mL, 6.27 mmol). The reaction was stirred at -78° C. for 1 hour. A solution of carbon tetrabromide (2.36 g, 7.12 mmol) in THF (6.3 mL) was added drop wise and the reaction was stirred at -78° C. for a further 1 hour. The reaction was quenched by the addition of saturated aqueous ammonium chloride. The mixture was extracted with iso-hexane (*2) and the combined extracts washed with saturated aqueous sodium chloride. The solution was dried over anhydrous MgSO4 and concentrated to a brown oil. The crude material was purified by automated column chromatography, eluting with iso-hexane. Fractions found to contain pure product were combined and solvent removed in vacuo to afford the desired compound as a yellow gum that solidified on standing, 0.97 g, 91.7%. |
84% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; Stage #2: With carbon tetrabromide In tetrahydrofuran; cyclohexane | 1.E [00301] Step E: 4-Fluoro-l-(triisopropylsilyl)-lH-pyrrolo[2,3-b]pyridine (28.0 g, 95.7 mmol) in THF (600 niL) at -78°C was treated dropwise with sec-butyllithium (150 rnL, 211 mmol; 1.4M in cyclohexane). The reaction was stirred at -78°C for 30 minutes. Perbromomethane (79.4 g, 239 mmol) in THF (100 mL) was then added dropwise. The reaction was stirred at -78°C for 1 hour and then quenched with saturated aqueous NH4Cl. The aqueous phase was extracted with hexanes. The combined organic phases were dried (MgSO4) and concentrated in vacuo. The oil obtained was purified by flash chromatography on silica gel eluting with hexanes to provide 5-bromo-4-fluoro-l-(triisopropylsilyl)-lH-pyrrolo[2,3-b]pyridine(30 g, 84% yield) as an oil, which solidified upon standing. 1H NMR (400 MHz, CDCl3) δ 8.28(d, IH), 7.26 (s, IH), 6.62 (d, IH), 1.86-1.78 (m, 3H), 1.11 (d, 18H). |
82% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 1.5h; Stage #2: With carbon tetrabromide In tetrahydrofuran at -78℃; for 1h; | 40.3 Step 3: Preparation of 5-bromo-4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3- b]pyridine A solution of 4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (15 g, 51.31 mmol) in THF (600 mL) was cooled to -78 °C. Then sec-butyllithium (1.2 M in cyclohexane, 64 mL, 76.97 mmol) was added slowly over 30 minutes and the mixture stirred for 1 hour. A solution of carbon tetrabromide (30.57 g, 92.36 mmol) in THF (45 mL) was added slowly and the reaction mass stirred for 1 hour at -78 °C. The reaction mixture was quenched by slow addition of aqueous saturated NH4Cl solution, followed by addition of MTBE (150 ml, 10 vol) and warming to ambient temperature. The two layers were separated and the aqueous layer extracted with MTBE (150 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography using 230-400 mesh silica gel and pet-ether to afford 5-bromo-4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (15.6 g, 82 % yield) as pale yellow liquid: MS (ES) m/z 371.3; 373.3 (1:1; M+H). |
63% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: With carbon tetrabromide In tetrahydrofuran; cyclohexane at -78℃; for 0.416667h; Further stages.; | |
61.4% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: With carbon tetrabromide In tetrahydrofuran; cyclohexane at -78℃; for 1h; | 51 [00370] S-BuLi (53.7 niL, 75.2 mmol, 1.4M in cyclohexane) was added to a solution of 4- fluoro-l-(triisopropylsilyl)-lH-pyrrolo[2,3-b]pyridine (10.0 g, 34.2 mmol, prepared as described in L'Heureux, et al. Org. Lett., 5(26), p. 5023 (2003)) in THF (250 mL) at -78°C, and the reaction was stirred at -78°C for 30 minutes. A solution Of CBr4 (28.3 g, 85.5 mmol) in THF (40 mL) was added next, and the reaction was stirred at this temperature for 1 hour. A saturated ammonium chloride solution (80 mL) was then added, and the reaction was extracted with hexane (200 mL), washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was then purified by column chromatography (hexane) to give 5-bromo-4-fluoro-l-(triisopropylsilyl)- lH-pyrrolo[2,3-b]pyridine (7.8 g, 61.4% yield). |
Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran at -70 - -65℃; for 0.5h; Inert atmosphere; Stage #2: With carbon tetrabromide In tetrahydrofuran for 1h; Inert atmosphere; | 4.b Starting material (3.3 g, 11.283 mmol) is initially introduced in 70 ml of absolute THF under protective-gas atmosphere and cooled to about -70° C. secBuLi solution (1.4M, 117.7 ml, 24.74 mmol) is subsequently added at -65 to -70° C. The mixture is stirred at this temperature for about a further 1/2 h, and a solution of tetrabromomethane (9.4 g, 28.115 mmol) in 80 ml of absolute THF is then added using a syringe. The mixture subsequently stirred for about a further 1 h.Saturated NH4Cl solution and water are added to the reaction mixture, which is then warmed to RT. The mixture is extracted with ethyl acetate, and the extract is subsequently washed with saturated NaCl solution, dried over Na2SO4 and evaporated to dryness. The dark oil obtained is adsorbed onto Si-60 and subjected to flash chromatography (Teledyne-Isco Combi Flash RF, column: Si-60, 120 g, eluent: petroleum ether, isocratic, flow rate: 85 ml/min, detection: UV254 nm), giving the product as oil. | |
Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.75h; Inert atmosphere; Stage #2: With carbon tetrabromide In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Inert atmosphere; | 13.2 (5-Bromo-4-fluoropyrrolo[2,3-b]pyridin-1-yl)-triisopropylsilane (P13-1b) To a solution of (4-fluoropyrrolo[2,3-b]pyridin-1-yl)-triisopropylsilane (1.0 g, 3.43 mmol) in distilled tetrahydrofuran (25 mL) was added sec-butyllithium (1.4 M in cyclohexane, 5.38 mL, 7.53 mmol) dropwise at -78 °C over 15 min under argon. The mixture was stirred at -78 °C for 30 min. To the reaction mixture was added a solution of carbon tetrabromide (2.84 g, 8.46 mmol) in distilled tetrahydrofuran (12.5 mL) dropwise at -78 °C. The reaction mixture was stirred at -78 °C for 30 min. The reaction was quenched with saturated aqueous ammonium chloride (50 mL) and the mixture was extracted with n-heptane (2 x 30 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated. The residue was purified by silica gel column chromatography eluting with n-heptane to afford the title compound (1.11 g, 3.00 mmol, 87%) as a white crystalline solid.LCMS Method H: 100%, tR=3.850 min, m/z = 371.0 [M+H]+ | |
Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With n-butyllithium In tetrahydrofuran; ethanol at -72℃; for 0.5h; Inert atmosphere; Stage #2: With carbon tetrabromide In tetrahydrofuran; ethanol at 20℃; for 1h; Inert atmosphere; | 30.3; 32 Step 3: Synthesis of compound 30-4 General procedure: Add compound 30-3 (400mg, 1.37mmol) and THF (5mL) to the reaction flask, replace the reaction liquid with nitrogen, cool to -72 in a dry ice/ethanol bath, and add sec-butyllithium (1.3M, 2.1mL, 2.74) dropwise mmol), after the addition, keep the temperature and stir for 0.5 hours. A solution of NFSI (518 mg, 1.64 mmol) in THF (3 mL) was added dropwise to the reaction solution. After the addition, the reaction solution was slowly raised to room temperature and stirred for 1 hour. The reaction solution was slowly poured into ice water for quenching, extracted twice with ethyl acetate, the organic phases were combined, washed with saturated brine, and concentrated under reduced pressure to obtain 800 mg of crude product 30-4, which was used directly in the next step without purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: With hexachloroethane In tetrahydrofuran; cyclohexane at -78℃; for 1h; | A Step A. 5-Chloro-4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine. sec- Butyllithium (12.0 mL, 1.3 M in cyclohexane, 15.6 mmol) was added dropwise to a -78 °C (dry ice/ethanol) solution of 4-fiuoro-1-(triisopropyIsilyl)-1H-pyrrolo[2,3-b]pyridine (2.00 g, 6.84 mmol) and THF (15 ml). The mixture was stirred for 0.5 h at -78 °C. Then a solution of perchloroethane (3.95 g, 16.7 mmol) and THF (45 ml) was added rapidly. The reaction mixture was stirred at -78 °C for another 1 hour and then quenched with sat. NH4CI (60 mL). The aqueous portion was extracted with ethyl acetate (60 mL x 4). The combined organic extracts were dried with anhydrous Na2SO4 filtered and concentrated to dryness under reduced pressure to give the product, which was purified by silica gel chromatography (eluent: petroleum ether: ethyl acetate = 1:0 to 0:1) to afford the title compound (1.92 g, 78%) as a white solid. LC-MS (ESI): mass calcd. for C16H24CIFN2Si 326.14 m/z found 327.2 [M+H]+. |
78% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: With hexachloroethane In tetrahydrofuran; cyclohexane at -78℃; for 1h; | A Step A. 5-Chloro-4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine. sec- Butyllithium (12.0 mL, 1.3 M in cyclohexane, 15.6 mmol) was added dropwise to a -78 °C (dry ice/ethanol) solution of 4-fiuoro-1-(triisopropyIsilyl)-1H-pyrrolo[2,3-b]pyridine (2.00 g, 6.84 mmol) and THF (15 ml). The mixture was stirred for 0.5 h at -78 °C. Then a solution of perchloroethane (3.95 g, 16.7 mmol) and THF (45 ml) was added rapidly. The reaction mixture was stirred at -78 °C for another 1 hour and then quenched with sat. NH4CI (60 mL). The aqueous portion was extracted with ethyl acetate (60 mL x 4). The combined organic extracts were dried with anhydrous Na2SO4 filtered and concentrated to dryness under reduced pressure to give the product, which was purified by silica gel chromatography (eluent: petroleum ether: ethyl acetate = 1:0 to 0:1) to afford the title compound (1.92 g, 78%) as a white solid. LC-MS (ESI): mass calcd. for C16H24CIFN2Si 326.14 m/z found 327.2 [M+H]+. |
72% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: With hexachloroethane In tetrahydrofuran; cyclohexane at -78℃; for 0.416667h; Further stages.; |
62% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran at -78℃; Stage #2: With hexachloroethane In tetrahydrofuran for 0.5h; | L [00293] 4-Fluoro-l-(triisopropylsilyl)-lH-pyrrolo[2,3-b]pyridine (3.0 g, 10.258 mmol) was placed in THF (15 mL) at -780C. S-BuLi (16.12 mL, 22.57 mmol) was then added dropwise and stirred for 30 minutes. Hexachloroethane (6.07 g, 25.6 mmol) in THF (10 mL) was then added rapidly, and the reaction was stirred for an additional 30 minutes. The reaction was quenched with saturated aqueous NH.C1 and extracted into hexanes. The combined organic fractions were dried, filtered and concentrated to give the crude product that was purified by column chromatography (hexanes) to give 5-chloro-4-fluoro-l-(triisopropylsilyl)-lH- pyrrolo[2,3-b]pyridine (2.1 g, 62% yield). |
Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: With hexachloroethane In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; | 24.3 4-Fluoro-1-[tris(propan-2-yl)silyl]-1 H-pyrrolo[2,3-b]pyridine (2g, 6.84mmol) in THF (80ml_) at -78 °C was treated drop wise with sec-butyllithium solution, 1.4M in cyclohexane (4.48 ml_, 6.27 mmol). The reaction was stirred at -78°C for 0.5 hours. A solution of hexachloroethane (4.05g, 17.1 mmol) in THF (20ml_) was added drop wise and the reaction was stirred at -78°C for a further 0.5 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride. The mixture was extracted with iso-hexane (x2) and the combined extracts washed with saturated aqueous sodium chloride. The solution was dried over anhydrous MgS04 and concentrated to a yellow gum. The crude material was stirred in THF (50ml_) and tetrabutylammonium fluoride solution, 1.0M in THF (6.84 ml_, 6.84 mmol) was added drop wise at RT. The reaction was stirred at RT for a further 1 hour before H20 and EtOAc were added. The organic layer was separated and the aqueous phase was extracted with another portion of EtOAc. The combined organic phases were washed with saturated aqueous sodium chloride, dried (MgSO4) and concentrated in vacuo to afford a pale orange solid. The crude residue was purified by automated flash chromatography eluting with iso-hexane to 40% EtOAc / iso-hexane. Fractions containing pure material were combined and solvent removed in vacuo to afford the desired product as a white solid 1.0g, 85.7%. | |
Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: With hexachloroethane In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; | 24.3 4-Fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine (2 g, 6.84 mmol) in THF (80 mL) at -78° C. was treated drop wise with sec-butyllithium solution, 1.4M in cyclohexane (4.48 mL, 6.27 mmol). The reaction was stirred at -78° C. for 0.5 hours. A solution of hexachloroethane (4.05 g, 17.1 mmol) in THF (20 mL) was added drop wise and the reaction was stirred at -78° C. for a further 0.5 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride. The mixture was extracted with iso-hexane (*2) and the combined extracts washed with saturated aqueous sodium chloride. The solution was dried over anhydrous MgSO4 and concentrated to a yellow gum. The crude material was stirred in THF (50 mL) and tetrabutylammonium fluoride solution, 1.0M in THF (6.84 mL, 6.84 mmol) was added drop wise at RT. The reaction was stirred at RT for a further 1 hour before H2O and EtOAc were added. The organic layer was separated and the aqueous phase was extracted with another portion of EtOAc. The combined organic phases were washed with saturated aqueous sodium chloride, dried (MgSO4) and concentrated in vacuo to afford a pale orange solid. The crude residue was purified by automated flash chromatography eluting with iso-hexane to 40% EtOAc/iso-hexane. Fractions containing pure material were combined and solvent removed in vacuo to afford the desired product as a white solid 1.0 g, 85.7%. | |
Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With n-butyllithium In tetrahydrofuran; ethanol at -72℃; for 0.5h; Inert atmosphere; Stage #2: With N-chloro-succinimide In tetrahydrofuran; ethanol at 20℃; for 1h; Inert atmosphere; | 30.3; 31 Step 3: Synthesis of compound 30-4 General procedure: Add compound 30-3 (400mg, 1.37mmol) and THF (5mL) to the reaction flask, replace the reaction liquid with nitrogen, cool to -72 in a dry ice/ethanol bath, and add sec-butyllithium (1.3M, 2.1mL, 2.74) dropwise mmol), after the addition, keep the temperature and stir for 0.5 hours. A solution of NFSI (518 mg, 1.64 mmol) in THF (3 mL) was added dropwise to the reaction solution. After the addition, the reaction solution was slowly raised to room temperature and stirred for 1 hour. The reaction solution was slowly poured into ice water for quenching, extracted twice with ethyl acetate, the organic phases were combined, washed with saturated brine, and concentrated under reduced pressure to obtain 800 mg of crude product 30-4, which was used directly in the next step without purification. | |
With hexachloroethane; sec.-butyllithium In tetrahydrofuran at -78℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran; cyclohexane at -78℃; for 0.416667h; Further stages.; | |
63.4% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 1h; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran at -78℃; for 1h; | 52.3 Step 3: Preparation of 5-Bromo-4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine General procedure: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine (833.0 mg, 2.85mmol)in THF (34 mL) at -78 °C was treated drop wise with sec-butyllithium solution,1.4M in cyclohexane (4.48 mL, 6.27 mmol). The reaction was stirred at -78 °Cfor 1 hour. A solution of carbon tetrabromide (2.36g, 7.l2mmol) in THF (6.3mL)was added drop wise and the reaction was stirred at -78 °C for a further 1 hour.The reaction was quenched by the addition of saturated aqueous ammonium chloride. The mixture was extracted with iso-hexane (x2) and the combined extracts washed with saturated aqueous sodium chloride. The solution was dried over anhydrous Mg504 and concentrated to a brown oil. The crude material waspurified by automated column chromatography, eluting with isohexane. Fractions found to contain pure product were combined and solvent removed in vacuo to afford the desired compound as a yellow gum that solidified on standing, 0.97g, 91.7%. |
32% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With 2,2,6,6-tetramethyl-piperidine; n-butyllithium In tetrahydrofuran at -78 - 0℃; for 0.75h; Inert atmosphere; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran at -78℃; for 0.25h; | 51 Synthesis of 4, 5-difluoro-] -(triisopropylsilyl)-]H-pyrrolo [2,3-b] pyridine [0595] To a stirred solution of 2,2’,6,6’-tetramethyl piperidine (9.65 g, 68 mmol) in THF (30 mL) at -78 °C under an argon atmosphere was added n-butyl lithium (27.3 mL, 68 mmol). The reaction mixture was stirred at 0 °C for 30 mm. Then 4-fluoro-1-(triisopropylsilyl)-1H- pyrrolo [2,3-bj pyridine (5 g, 17 mmol) in THF (40 mL) was added and stirred for 15 mm, again N-fluorobenzene sulfonimide (13.5 g, 43 mmol) in THF (30 mL) was added to the reaction mixture at -78 °C. The reaction mixture was stirred for 15 mm at -78 °C. After consumption of starting material (by TLC), the reaction mixture was quenched with saturated ammonium chloride solution (50 mL) and extracted with EtOAc (2 x 100 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by column chromatography using 20% Hexane to afford 4,5- difluoro-1-(triisopropylsilyl)-1H-pyrrolo [2,3-bj pyridine (1.7 g, 32%) as an off-white solid. ‘H NMR (CDC13, 500 MHz): 8.16 (dd, 1H), 7.29 (d, 1H), 6.64 (t, 1H), 1.87-1.73 (m, 3H), 1.10 (d, 18H); TLC: Hexane (R1 0.7). |
Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran; cyclohexane at -78℃; for 0.333333h; | 13.A [00342] Step A: 4-fluoro-l-(triisopropylsilyl)-lH-pyrrolo[2,3-b]pyridine (2.00 g, 6.84 mmol) in THF (20 mL) was added to S-BuLi (12.5 mL, 15.0 mmol, 1.4M in cyclohexane) at -78°C for 30 minutes. N-Fluoro-N-(phenylsulfonyl)benzenesulfonamide (5.39 g, 17.1 mmol) in THF (15 mL) was added, and it was stirred at -78°C for 20 minutes. A saturated ammonium chloride solution (20 mL) was added and extracted with hexanes (50 mL), washed with brine, and dried over sodium sulfate. After removal of the solvent, the residue was dissolved in THF (10 mL), and TBAF (6.84 niL, 6.84 mmol) in THF (6.84 niL, 6.84 mmol) was added. The reaction was stirred at room temperature for 10 minutes, and water (20 mL) and ethyl acetate (30 mL) were added. The organic layer was separated, washed with brine and dried over sodium sulfate. After removal of the solvent, the residue was purified by chromatography (ethyl acetate) to give 4,5-difluoro-lH-pyrrolo[2,3-b]pyridine (0.63 g, 60% yield) as a solid. LCMS (APCI+) m/z 155.1 (M+H)+. | |
800 mg | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With n-butyllithium In tetrahydrofuran; ethanol at -72℃; for 0.5h; Inert atmosphere; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran; ethanol at 20℃; for 1h; Inert atmosphere; | 30.3 Step 3: Synthesis of compound 30-4 Add compound 30-3 (400mg, 1.37mmol) and THF (5mL) to the reaction flask, replace the reaction liquid with nitrogen, cool to -72 in a dry ice/ethanol bath, and add sec-butyllithium (1.3M, 2.1mL, 2.74) dropwise mmol), after the addition, keep the temperature and stir for 0.5 hours. A solution of NFSI (518 mg, 1.64 mmol) in THF (3 mL) was added dropwise to the reaction solution. After the addition, the reaction solution was slowly raised to room temperature and stirred for 1 hour. The reaction solution was slowly poured into ice water for quenching, extracted twice with ethyl acetate, the organic phases were combined, washed with saturated brine, and concentrated under reduced pressure to obtain 800 mg of crude product 30-4, which was used directly in the next step without purification. |
With sec.-butyllithium; N-fluorobis(benzenesulfon)imide In tetrahydrofuran at -78℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: With (R)-camphorsulfonyl oxaziridine In tetrahydrofuran; cyclohexane at -78℃; for 0.416667h; Further stages.; | |
51.8% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: With (1R)-(−)-(10-camphorsulfonyl)oxaziridine In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; | 44 [00358] sec-Butyl lithium (8.06 mL, 11.3 mmol, 1.4 M in cyclohexane) was added dropwise to 4-fluoro-l-(triisopropylsilyl)-lH-pyrrolo[2,3-b]pyridine (1.5 g, 5.13 mmol, prepared as described in L'Heureux, et al., Org. Lett., 5(26) p. 5023 (2003)) in THF (100 mL) at -78°C. The reaction was stirred for 30 minutes. (lR)-(-)-(10-camphorsulfonyl)oxaziridine (2.94 g, 12.8 mmol) in THF (10 mL) was added rapidly, and the reaction was stirred at -78°C for 30 minutes. A solution of saturated ammonium chloride (50 mL) was added, and the reaction mixture was allowed to reach room temperature. After one hour, the aqueous phase was extracted with AcOEt, dried over MgSO4 and concentrated to a solid, which was triturated in ether. The solid (most of the camphor side product) was filtered off, and the filtrate concentrated and purified by chromatography (25M, toluene/AcOEt 95/5) to yield a paste. The paste was triturated with hexanes, and the filtrate was concentrated to dryness to yield 4-fluoro-l-(triisopropylsilyl)-lH- pyrrolo[2,3-b]pyridin-5-ol (820 mg, 51.8% yield) as an oil, which solidified upon standing. [00359] 2-Bromopropane (120 mg, 0.973 mmol) and potassium carbonate (448 mg, 3.24 mmol) were added to 4-fluoro-l-(triisopropylsilyl)-lH-pyrrolo[2,3-b]pyridin-5-ol (200 mg, 0.648 mmol) in DMF (3 mL). The reaction was heated to 800C in a sealed tube for 18 hours and then cooled down. The reaction mixture was concentrated to dryness. The mixture was then suspended in DCM and filtered. The filtrate was concentrated and purified by chromatography (SP4, 12+M, water/ACN 80/20-> 10/90, 20CV) to yield 4-fluoro-5-isopropoxy-l- (triisopropylsilyl)-lH-pyrrolo[2,3-b]pyridine (65 mg, 42%) as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: sec-butyllithium / tetrahydrofuran; cyclohexane / 0.5 h / -78 °C 1.2: 30 percent / tosyl azide / tetrahydrofuran; cyclohexane / 0.42 h / -78 °C 2.1: 100 percent / H2 / Pd/C / ethyl acetate / 18 h / 20 °C / 760.05 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With tetrabutyl ammonium fluoride; In tetrahydrofuran; at 0 - 20℃; for 1h;Inert atmosphere; | [0722] To a stirred solution of 4-fluoro-i-(triisopropylsilyl)-1H-pyrrolo [2,3-bj pyridine (3 g, 10 mmol) in THF (15 mL) at 0 C under an argon atmosphere was added tetra butyl ammonium fluoride 1M in THF (10.5 mL). The reaction mixture was warmed to room temperature and stirred for 1 h. After consumption of starting material (by TLC), the reactionmixture was diluted with water (50 mL) and extracted with EtOAc (2 x 100 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by column chromatography using 20%EtOAc: Hexane to afford 4-fluoro-1H-pyrrolo [2,3-bj pyridine (1.3 g, 94%) as an off-white solid. ?H NMR (CDC13, 400 MHz): 10.52 (brs, 1H), 8.30-8.25 (m, 1H), 7.32-7.30 (m, 1H), 6.81 (dd, 1H), 6.59 (s, 1H); TLC: 20% EtOAc Hexane (R 0.2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: 4-bromo-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With tert.-butyl lithium In tetrahydrofuran; pentane at -78℃; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran; pentane at -78℃; for 2h; | 1.D [00300] Step D: 4-Bromo-l-(triisopropylsilyl)-lH-pyrrolo[2,3-b]pyridine (50 g, 141.5 mmol) in THF (2 L) at -78°C was treated dropwise with tert-butyllithium (166.5 mL, 283.0 mmol, 1.7M in pentane). The reaction was then stirred for 15 minutes. N-Fluoro-N- (phenylsulfonyl)benzenesulfonamide (49.08 g, 155.6 mmol) in THF (200 mL) was then added dropwise, and the mixture was stirred at -78°C. After 2 hours, the reaction was quenched at - 78°C with saturated aqueous NH4Cl (200 mL). The aqueous phase was extracted with hexanes.The combined hexane phases were dried (MgSO4) and passed through a plug of silica gel eluting with hexanes. The combined hexanes fractions were concentrated in vacuo to provide 4-fluoro- l-(triisopropylsilyl)-lH-pyrrolo[2,3-b]pyridine (36.1 g, 87% yield) as an oil. 1H NMR (400 MHz, CDCl3) δ 8.18 (dd, IH), 7.25 (d, IH), 6.76 (dd, IH), 1.86-1.81 (m, 3H), 1.13 (d, 18H). |
84% | Stage #1: 4-bromo-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With tert.-butyl lithium In tetrahydrofuran; pentane at -78℃; for 0.0833333h; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran; pentane at -78℃; for 0.75h; | |
78.5% | Stage #1: 4-bromo-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With n-butyllithium In diethyl ether; hexane at -78 - -5℃; for 1.25h; Inert atmosphere; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran; diethyl ether; hexane at -78℃; for 3h; | 6.2 Step 2: Preparation of 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine n-Butyllithium solution, 2.5M in hexanes (2.52mL, 11.3mmol) was added dropwise to a solution of 4-bromo-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine (2.0g, 5.66mmol) in Et20 (6OmL) at -78°C under a nitrogen atmosphere, and the mixture stirred for 30 minutes at -78°C and for 45mins at -5°C to give a pale yellow solution. The resulting solution was cooled to -78°C, and a solution of(2.05g, 6.51mmol) in THF (10mL) was addeddrop wise. The mixture stirred for a further 3 hours at -78°C, and then quenched by the addition of saturated aqueous ammonium chloride solution. The organic layer was separated and the aqueous layer was extracted with Et20 (2x5OmL) and the combined extracts washed with saturated aqueous sodium chloride solution. The solution was dried over anhydrous MgSO4 and concentrated toyellow gum. The crude material was purified by flash chromatography, eluting with iso-hexane. Fractions found to contain pure product were combined and solvent removed in vacuo to afford the desired compound as a colourless oil, 1.3g, 78.5%. |
78.5% | Stage #1: 4-bromo-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With n-butyllithium In diethyl ether; hexane at -78 - -5℃; for 1.25h; Inert atmosphere; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran; diethyl ether; hexane at -78℃; for 3h; Inert atmosphere; | 6.2 Step 2: Preparation of 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine n-Butyllithium solution, 2.5M in hexanes (2.52 mL, 11.3 mmol) was added drop wise to a solution of 4-bromo-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine (2.0 g, 5.66 mmol) in Et2O (60 mL) at -78° C. under a nitrogen atmosphere, and the mixture stirred for 30 minutes at -78° C. and for 45 mins at -5° C. to give a pale yellow solution. The resulting solution was cooled to -78° C., and a solution of N-fluorobis(phenylsulphonyl)amine (2.05 g, 6.51 mmol) in THF (10 mL) was added drop wise. The mixture stirred for a further 3 hours at -78° C., and then quenched by the addition of saturated aqueous ammonium chloride solution. The organic layer was separated and the aqueous layer was extracted with Et2O (2*50 mL) and the combined extracts washed with saturated aqueous sodium chloride solution. The solution was dried over anhydrous MgSO4 and concentrated to a yellow gum. The crude material was purified by flash chromatography, eluting with iso-hexane. Fractions found to contain pure product were combined and solvent removed in vacuo to afford the desired compound as a colourless oil, 1.3 g, 78.5%. |
66% | Stage #1: 4-bromo-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With n-butyllithium In diethyl ether at -78℃; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran at -78℃; Further stages.; | |
52% | Stage #1: 4-bromo-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With n-butyllithium In tetrahydrofuran; ethanol at -72℃; for 0.5h; Inert atmosphere; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran; ethanol at 20℃; for 1h; Inert atmosphere; | 30.2 Step 2: Synthesis of compound 30-3 Add compound 30-2 (3.92g, 11.1mmol) and THF (25mL) to the reaction flask, replace the reaction liquid with nitrogen, cool to -72 in a dry ice/ethanol bath, and add n-butyllithium (2.5M, 8.9mL, 22.2mmol), after the addition, keep warm and stir for 0.5 hour. A solution of NFSI (4.2 g, 13.3 mmol) in THF (10 mL) was added dropwise to the reaction solution. After the addition, the reaction solution was slowly raised to room temperature and stirred for 1 hour. The reaction solution was slowly poured into ice water for quenching, extracted twice with ethyl acetate, and the organic phases were combined, washed with saturated brine, and concentrated under reduced pressure and purified by silica gel column to obtain 1.69 g of product 30-3. Yield: 52%. |
47% | Stage #1: 4-bromo-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With n-butyllithium In tetrahydrofuran at -78℃; for 0.25h; Inert atmosphere; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran at -78℃; for 2h; | 51 Synthesis of 4-fluoro-] -(triisopropylsilyl)-]H-pyrrolo [2,3-b] pyridine [0594] To a stirred solution of 4-bromo-1-(triisopropylsilyl)-1H-pyrrolo [2,3-bj pyridine (27 g, 76 mmol) in THF (772 mL) at -78 °C under an argon atmosphere was added n-BuLi (9.79 g, 153 mmol). The reaction mixture was stirred for 15 mm. Then Nfluorobenzenesulfonimide (26.50 g, 84 mmol) in THF (416 mL) was added to the reaction mixture at -78 °C. The reaction mixture was stirred for 2 h. After consumption of starting material (by TLC), the reaction mixture was quenched with saturated ammonium chloride solution (400 mL) and extracted with hexane (2 x 400 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by column chromatography using Hexane to afford 4-fluoro-1-(triisopropylsilyl)-1H- pyrrolo [2,3-bj pyridine (10.5 g, 47%) as colorless liquid. ‘H NMR (CDC13, 500 MHz): 8.18 (dd, 1H), 7.25 (s, 1H), 6.75 (dd, 1H), 6.63 (d, 1H), 1.90-1.80 (m, 3H), 1.12 (d, 18H); TLC: Hexane (Rj: 0.7). |
40.6% | Stage #1: 4-bromo-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With n-butyllithium In tetrahydrofuran; hexane at -78℃; Stage #2: With N-fluorobenzene sulfonamide In tetrahydrofuran; hexane for 1h; | 40.2 Step 2: Preparation of 4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine A solution of 4-bromo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (46 g, 133 mmol) in THF (800 ml) was cooled to -78 °C. Then n-butyllithium (1.2 M in hexanes, titrated by diphenylacetic acid method) (167 mL, 200 mmol) was added slowly using a syringe over ~1 hour. The reaction mixture was stirred for 15 minutes at the same temperature. Then a solution of N-fluorobenzenesulfonamide (84 g, 266 mmol) in THF (235 ml) was added slowly, and the reaction stirred for 1 hour at the same temperature. The reaction was quenched with aqueous saturated NH4Cl solution and diluted with MTBE (235 mL). The reaction was slowly raised to ambient temperature, the two layers were seperated, and aqueous layer was extracted with MTBE (235 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography using 230-400 mesh silica gel and pet-ether to afford 4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (15.5 g, 40.6 % yield) as a pale yellow liquid: MS (ES) m/z 293.4 (M+H). |
Stage #1: 4-bromo-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With pyridine; n-butyllithium In diethyl ether at -70 - -65℃; for 0.5h; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran; diethyl ether at -70 - -65℃; for 2h; | 4.a Preparation of 1-{2-amino-6-[4-fluoro-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo-[2,3-b]pyridin-3-yl]pyrimidin-4-yl}-1-(3-fluorophenyl)ethanol (“A106”) [analogous to “A9”]; 4-Bromo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (5 g, 13.38 mmol) is initially introduced in 75 ml of absolute ether, cooled to about -70° C., and BuLi solution (1.6 M, 18.4 ml, 29.44 mmol) is slowly added at -65 to -70° C. using a syringe. The mixture is stirred at this temperature for about a further ½ h, and a solution of N-fluorodibenzenedisulfonimide (5.7 g, 17.53 mmol) in 75 ml of absolute THF is then added to the reaction solution. The mixture is subsequently stirred for 2 h at low temperature. Saturated NH4Cl solution and water are added to the reaction mixture, which is then warmed to RT. The mixture is extracted 3× with ether. The combined organic phases are washed with saturated NaCl solution, dried over Na2SO4 and evaporated to dryness. Crude product is adsorbed onto Si-60 and purified by flash chromatography (Teledyne-Isco Combi Flash RF, column: Si-60, 120 g, eluent: PE isocratic, flow rate: 85 ml/min, detection: UV 220 nm), giving the product as an oil. | |
Stage #1: 4-bromo-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran at -78 - 10℃; for 11.5h; Inert atmosphere; | 25 (4-fluoropyrrolo[2,3-b]pyridin-1-yl)-triisopropyl-silane To a solution of (4-bromopyrrolo[2,3-b]pyridin-1-yl)-triisopropyl-silane (15 g, 42.45 mmol, 1 eq) in THF(150 mL) was added n-BuLi (2.5 M, 33.96 mL, 2 eq) at -78°C under N2. The mixture was stirred at -78 °C for 0.5 h under N2. A solution of NFSI (20 g, 63.42 mmol, 1.49 eq) in THF (50 mL) was added at -78 °C. The mixture was stirred at 10 °C for 11.5 h under N2. LCMS showed no starting material. TLC (Petroleum ether/EtOAc=1:0, Rf= 1)showed new spots was observed. The reaction was quenched with saturated aqueous NH4Cl (30mL). The mixture was concentrated in reduced pressure. The residue was diluted with H2O (20 mL). The aqueous phase was extracted with EtOAc (50 mL x 3) and washed with water (50ml x 3). The organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/EtOAc=1:0). The product (4-fluoropyrrolo[2,3-b]pyridin-1-yl)-triisopropyl-silane (9.3 g, 28.62 mmol, 67.42% yield, 90% purity) was obtained as yellow brown oil. LCMS (ESI) m/z 293.2 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: With 4-toluenesulfonyl azide In tetrahydrofuran; cyclohexane at -78℃; for 0.416667h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 38% 2: 26% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: With N-Bromosuccinimide In tetrahydrofuran; cyclohexane at -78℃; for 0.416667h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With pyridinium hydrobromide perbromide In <i>tert</i>-butyl alcohol at 20℃; for 72h; | E.1 PREPARATION E 4-Fluoro-l,3-dihvdro-pyrrolor2,3-blpyridin-2-one El. 3,3-Dibromo-4-fluoro-l,3-dihvdro-pyrrolor2,3-blpyridin-2-one; To a solution of 4-fluoro-l-triisopropylsilanyl-lH-pyrτolo[2,3-b]pyridine (Org Lett 2003, 5, 5023-5026, l.Og, 3.4mmol) in tert-butanol (25ml) was added portionwise pyridine tribromide (3.8g, 11.97mmol) and this mixture was stirred at room temperature for 3 days. The solvent was removed in vacuo, water and ethyl acetate was added, the mixture was filtered under suction then the organic layer separated. The aqueous fraction was extracted twice with ethyl acetate then the organic liquors were combined and concentrated. The crude product was purified on a silica Biotage column, eluting with petrol/ ethyl acetate to furnish the clean product (312mg, 29%). |
29% | With pyridinium hydrobromide perbromide In <i>tert</i>-butyl alcohol at 20℃; for 72h; | E.E1 PREPARATION E4-Fluoro- 1 ,3 -dihydro-pyrrolo [2,3 -b]pyridin-2-oneEl. 3,3-Dibromo-4-fluoro-l,3-dihvdro-pyrrolo[2,3-blpyridin-2-oneTo a solution of 4-fluoro-l-triisopropylsilanyl-lH-pyrrolo[2,3-b]pyridine (OrgLett 2003, 5, 5023-5026, l.Og, 3.4mmol) in tert-butanol (25ml) was added portionwise pyridine tribromide (3.8g, 11.97mmol) and this mixture was stirred at room temperature for 3 days. The solvent was removed in vacuo, water and ethyl acetate was added, the mixture was filtered under suction then the organic layer separated. The aqueous fraction was extracted twice with ethyl acetate then the organic liquors were combined and concentrated. The crude product was purified on a silica Biotage column, eluting with petrol/ ethyl acetate to furnish the clean product (312mg, 29%). |
With pyridinium hydrobromide perbromide In <i>tert</i>-butyl alcohol at 20℃; for 72h; | 4.4A PREPARATION 4; 4-Fluoro-l,3-dihvdro-pyrrolor2,3-blpyridin-2-one 4A. 3,3-Dibromo-4-fluoro-l,3-dihydro-pyrrolor2,3-blpyridin-2-oneTo a solution of 4-fluoro-l-triisopropylsilanyl-lH-pyrτolo[2,3-b]pyridine (Org Lett 2003, 5, 5023-5026, l.Og, 3.4mmol) in tert-butanol (25ml) was added portionwise pyridine tribromide (3.8g, 11.97mmol) and this mixture was stirred at room temperature for 3 days. The solvent was removed in vacuo, water and ethyl acetate was added, the mixture was filtered under suction then the organic layer separated. The aqueous fraction was extracted twice with ethyl acetate then the organic liquors were combined and concentrated. The crude product was purified on a silica Biotage column, eluting with petrol/ ethyl acetate to furnish the clean product (312mg, 29%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With 1-methyl-pyrrolidin-2-one; triethylamine at 160℃; for 2h; microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With 1-methyl-pyrrolidin-2-one; triethylamine at 160℃; for 2h; microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With 1-methyl-pyrrolidin-2-one; triethylamine at 160℃; for 2h; microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | With 1-methyl-pyrrolidin-2-one; triethylamine at 160℃; for 2h; microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With 1-methyl-pyrrolidin-2-one; triethylamine at 160℃; for 2h; microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With 1-methyl-pyrrolidin-2-one; triethylamine at 160℃; for 2h; microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With 1-methyl-pyrrolidin-2-one; triethylamine at 160℃; for 2h; microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Stage #1: 4-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine With n-butyllithium In diethyl ether at -78℃; Stage #2: With N-fluorobis(benzenesulfon)imide In tetrahydrofuran at -78℃; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: 99 percent / sodium hydride / tetrahydrofuran / 3 h / 80 °C 2.1: tert-butyllithium / tetrahydrofuran; pentane / 0.08 h / -78 °C 2.2: 84 percent / N-fluorobenzenesulfonimide / pentane; tetrahydrofuran / 0.75 h / -78 °C | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.25 h / 0 °C 1.2: 1 h / 0 - 20 °C 2.1: n-butyllithium / hexane; diethyl ether / 1.25 h / -78 - -5 °C / Inert atmosphere 2.2: 3 h / -78 °C | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.25 h / 0 °C 1.2: 1 h / 0 - 20 °C 2.1: n-butyllithium / hexane; diethyl ether / 1.25 h / -78 - -5 °C / Inert atmosphere 2.2: 3 h / -78 °C / Inert atmosphere |
Multi-step reaction with 2 steps 1.1: sodium hydride / mineral oil; tetrahydrofuran / 0.83 h / 0 - 5 °C 1.2: 3.33 h / 70 °C 2.1: n-butyllithium / tetrahydrofuran; hexane / -78 °C 2.2: 1 h | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 1.5 h / 20 °C / Inert atmosphere; Cooling with ice 2.1: n-butyllithium / ethanol; tetrahydrofuran / 0.5 h / -72 °C / Inert atmosphere 2.2: 1 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 12 h / 0 - 10 °C 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 11.5 h / -78 - 10 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: 54 percent / tetramethylammonium bromide; methanesulfonic anhydride / dimethylformamide / 4 h / 0 - 23 °C 2.1: 99 percent / sodium hydride / tetrahydrofuran / 3 h / 80 °C 3.1: tert-butyllithium / tetrahydrofuran; pentane / 0.08 h / -78 °C 3.2: 84 percent / N-fluorobenzenesulfonimide / pentane; tetrahydrofuran / 0.75 h / -78 °C | ||
Multi-step reaction with 3 steps 1.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 18 h / 20 °C / Inert atmosphere 2.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 °C / Inert atmosphere 2.2: 1 h / 0 - 20 °C 3.1: n-butyllithium / tetrahydrofuran / 0.25 h / -78 °C / Inert atmosphere 3.2: 2 h / -78 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: 99 percent / sodium hydride / tetrahydrofuran / 3 h / 80 °C 2.1: tert-butyllithium / tetrahydrofuran; pentane / 0.08 h / -78 °C 2.2: 84 percent / N-fluorobenzenesulfonimide / pentane; tetrahydrofuran / 0.75 h / -78 °C | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.25 h / 0 °C 1.2: 1 h / 0 - 20 °C 2.1: n-butyllithium / hexane; diethyl ether / 1.25 h / -78 - -5 °C / Inert atmosphere 2.2: 3 h / -78 °C | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.25 h / 0 °C 1.2: 1 h / 0 - 20 °C 2.1: n-butyllithium / hexane; diethyl ether / 1.25 h / -78 - -5 °C / Inert atmosphere 2.2: 3 h / -78 °C / Inert atmosphere |
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 °C / Inert atmosphere 1.2: 1 h / 0 - 20 °C 2.1: n-butyllithium / tetrahydrofuran / 0.25 h / -78 °C / Inert atmosphere 2.2: 2 h / -78 °C | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / mineral oil; tetrahydrofuran / 0.83 h / 0 - 5 °C 1.2: 3.33 h / 70 °C 2.1: n-butyllithium / tetrahydrofuran; hexane / -78 °C 2.2: 1 h | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 1.5 h / 20 °C / Inert atmosphere; Cooling with ice 2.1: n-butyllithium / ethanol; tetrahydrofuran / 0.5 h / -72 °C / Inert atmosphere 2.2: 1 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 12 h / 0 - 10 °C 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 11.5 h / -78 - 10 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In 1-methyl-pyrrolidin-2-one at 160℃; for 2h; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With triethylamine In 1-methyl-pyrrolidin-2-one at 160℃; for 2h; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In 1-methyl-pyrrolidin-2-one at 160℃; for 2h; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran / 0.5 h / -70 - -65 °C / Inert atmosphere 1.2: 1 h / Inert atmosphere 2.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane / 100 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: sec.-butyllithium / tetrahydrofuran / 0.5 h / -70 - -65 °C / Inert atmosphere 1.2: 1 h / Inert atmosphere 2.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane / 100 °C / Inert atmosphere 3.1: palladium diacetate; copper(l) iodide; tri-tert-butyl phosphine / toluene; acetonitrile / 80 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: sec.-butyllithium / tetrahydrofuran / 0.5 h / -70 - -65 °C / Inert atmosphere 1.2: 1 h / Inert atmosphere 2.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 20 °C 4.1: potassium hydroxide; iodine / N,N-dimethyl-formamide / 2 h / 20 °C 5.1: dmap; triethylamine / dichloromethane / 3 h / 20 °C 6.1: caesium carbonate / palladium diacetate; tri-tert-butyl phosphine / toluene; acetonitrile / 0.17 h / 80 °C 7.1: potassium carbonate; methanol / 1 h / 20 °C 8.1: potassium carbonate / 2-methoxy-ethanol / 3 h / 130 °C 9.1: hydrogenchloride / 1,4-dioxane / 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: sec.-butyllithium / tetrahydrofuran / 0.5 h / -70 - -65 °C / Inert atmosphere 1.2: 1 h / Inert atmosphere 2.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: sec.-butyllithium / tetrahydrofuran / 0.5 h / -70 - -65 °C / Inert atmosphere 1.2: 1 h / Inert atmosphere 2.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 20 °C 4.1: potassium hydroxide; iodine / N,N-dimethyl-formamide / 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: sec.-butyllithium / tetrahydrofuran / 0.5 h / -70 - -65 °C / Inert atmosphere 1.2: 1 h / Inert atmosphere 2.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 20 °C 4.1: potassium hydroxide; iodine / N,N-dimethyl-formamide / 2 h / 20 °C 5.1: dmap; triethylamine / dichloromethane / 3 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: sec.-butyllithium / tetrahydrofuran / 0.5 h / -70 - -65 °C / Inert atmosphere 1.2: 1 h / Inert atmosphere 2.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 20 °C 4.1: potassium hydroxide; iodine / N,N-dimethyl-formamide / 2 h / 20 °C 5.1: dmap; triethylamine / dichloromethane / 3 h / 20 °C 6.1: caesium carbonate / palladium diacetate; tri-tert-butyl phosphine / toluene; acetonitrile / 0.17 h / 80 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1.1: sec.-butyllithium / tetrahydrofuran / 0.5 h / -70 - -65 °C / Inert atmosphere 1.2: 1 h / Inert atmosphere 2.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 20 °C 4.1: potassium hydroxide; iodine / N,N-dimethyl-formamide / 2 h / 20 °C 5.1: dmap; triethylamine / dichloromethane / 3 h / 20 °C 6.1: caesium carbonate / palladium diacetate; tri-tert-butyl phosphine / toluene; acetonitrile / 0.17 h / 80 °C 7.1: potassium carbonate; methanol / 1 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: sec.-butyllithium / tetrahydrofuran / 0.5 h / -70 - -65 °C / Inert atmosphere 1.2: 1 h / Inert atmosphere 2.1: sodium carbonate / tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane / 100 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 20 °C 4.1: potassium hydroxide; iodine / N,N-dimethyl-formamide / 2 h / 20 °C 5.1: dmap; triethylamine / dichloromethane / 3 h / 20 °C 6.1: caesium carbonate / palladium diacetate; tri-tert-butyl phosphine / toluene; acetonitrile / 0.17 h / 80 °C 7.1: potassium carbonate; methanol / 1 h / 20 °C 8.1: potassium carbonate / 2-methoxy-ethanol / 3 h / 130 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: methyl iodide In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; | 17.1 4--Fluoro-5-methylpyrrolo[2,3-b]pyridin-1-yl)-triisopropylsilane (P17-1a) To a solution of (4-fluoropyrrolo[2,3-b]pyridin-1-yl)-triisopropylsilane (3.00 g, 10.27 mmol) in freshly distilled tetrahydrofuran (75 mL) was added sec-butyllithium (1.4 M in cyclohexane, 16.14 mL, 22.6 mmol) dropwise at -78 °C over 30 min. To the mixture was added a solution of iodomethane (3.2 mL, 51.4 mmol) in freshly distilled tetrahydrofuran (30 mL) dropwise at -78 °C over 30 min. The reaction mixture was stirred at -78 °C for 30 min. The reaction was quenched with saturated aqueous ammonium chloride (100 mL) and the mixture was extracted with n-heptane (3 x 80 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated. The residue was purified by silica gel column chromatography eluting with n-heptane to afford the title compound (2.69 g, 8.78 mmol, 85%) as a white crystalline solidLCMS Method A: 93%, tR=2.320 min, m/z = 307.3 [M+H]+ |
Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: methyl iodide In tetrahydrofuran; cyclohexane at -78℃; for 0.75h; | 87.1 sec-Butyllithium solution, 1.4M in cyclohexane (8.76ml_, 12.26mmol) was added drop wise to a solution of 4-fluoro-1 -triisopropylsilanyl-1 H-pyrrolo[2,3-b]pyridine (2.05g, 7.01 mmol) in THF (75ml_) at -78°C. The reaction was stirred at -78°C for 30 minutes and then methyl iodide (2.49g, 1.09ml_, 17.52mmol) was added drop wise and the reaction was stirred at -78°C for a further 45 minutes. The reaction was quenched by the addition of saturated aqueous ammonium chloride (50ml_) and the reaction allowed to attain RT. The mixture was extracted with EtOAc (x3) and the combined extracts washed with saturated aqueous sodium chloride, dried (MgSO4) and concentrated in vacuo. The residue was taken up in THF (50ml_) and tetrabutylammonium fluoride solution, 1.0M in THF (7.01 mL, 7.01 mmol) was added drop wise at RT. The reaction mixture was stirred at RT for 30 minutes and then partitioned between H2O and EtOAc. The organic layer was separated and the aqueous was extracted with more EtOAc. The combined organic phases were washed with saturated aqueous sodium chloride, dried (MgSO4) and concentrated in vacuo. The residue was stirred in DCM/iso-hexane (1 :1 ), filtered and washed with DCM/iso-hexane (1 :1 ) prior to drying in vacuo. This afforded the title compound as a white powder, 0.561 g, 53.3% | |
Stage #1: 4-fluoro-1-[tris(propan-2-yl)silyl]-1H-pyrrolo[2,3-b]pyridine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -78℃; for 0.5h; Stage #2: methyl iodide In tetrahydrofuran; cyclohexane at -78℃; for 0.75h; | 87.1 sec-Butyllithium solution, 1.4M in cyclohexane (8.76 mL, 12.26 mmol) was added drop wise to a solution of 4-fluoro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (2.05 g, 7.01 mmol) in THF (75 mL) at -78° C. The reaction was stirred at -78° C. for 30 minutes and then methyl iodide (2.49 g, 1.09 mL, 17.52 mmol) was added drop wise and the reaction was stirred at -78° C. for a further 45 minutes. The reaction was quenched by the addition of saturated aqueous ammonium chloride (50 mL) and the reaction allowed to attain RT. The mixture was extracted with EtOAc (*3) and the combined extracts washed with saturated aqueous sodium chloride, dried (MgSO4) and concentrated in vacuo. The residue was taken up in THF (50 mL) and tetrabutylammonium fluoride solution, 1.0M in THF (7.01 mL, 7.01 mmol) was added drop wise at RT. The reaction mixture was stirred at RT for 30 minutes and then partitioned between H2O and EtOAc. The organic layer was separated and the aqueous was extracted with more EtOAc. The combined organic phases were washed with saturated aqueous sodium chloride, dried (MgSO4) and concentrated in vacuo. The residue was stirred in DCM/iso-hexane (1:1), filtered and washed with DCM/iso-hexane (1:1) prior to drying in vacuo. This afforded the title compound as a white powder, 0.561 g, 53.3%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 0.5 h / -78 °C 1.2: 0.75 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 0.5 h / -78 °C 1.2: 0.75 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 0.5 h / -78 °C 1.2: 0.5 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 1 h / -78 °C 1.2: 1 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 1 h / -78 °C 1.2: 1 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C | ||
Multi-step reaction with 2 steps 1: sec.-butyllithium / tetrahydrofuran; cyclohexane / -78 °C 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C |
Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 0.75 h / -78 °C / Inert atmosphere 1.2: 0.5 h / -78 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 1.5 h / -78 °C 1.2: 1 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 4.5 h / 0 - 5 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 1 h / -78 °C 1.2: 1 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C 3.1: nitric acid / 0.5 h / 0 °C | ||
Multi-step reaction with 3 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 1 h / -78 °C 1.2: 1 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C 3.1: nitric acid / water / 0.5 h / 0 °C | ||
Multi-step reaction with 3 steps 1: sec.-butyllithium / tetrahydrofuran; cyclohexane / -78 °C 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C 3: nitric acid / 0.5 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 1 h / -78 °C 1.2: 1 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C 3.1: nitric acid / 0.5 h / 0 °C 4.1: tin(II) chloride dihdyrate; hydrogenchloride / water / 1 h / 0 - 20 °C | ||
Multi-step reaction with 4 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 1 h / -78 °C 1.2: 1 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C 3.1: nitric acid / water / 0.5 h / 0 °C 4.1: tin(II) chloride dihdyrate; hydrogenchloride / water / 1 h / 0 - 20 °C | ||
Multi-step reaction with 4 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C 3.1: nitric acid / 0.5 h / 0 °C 4.1: hydrogenchloride; tin(ll) chloride / 0 - 20 °C 4.2: pH 7 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 0.5 h / -78 °C 1.2: 0.5 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 0.5 h / -78 °C 1.2: 0.5 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran / -78 °C 1.2: 0.5 h 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 °C |
Multi-step reaction with 2 steps 1: hexachloroethane; sec.-butyllithium / tetrahydrofuran / -78 °C 2: tetrabutyl ammonium fluoride / tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: n-butyllithium; 2,2,6,6-tetramethyl-piperidine / tetrahydrofuran / 0.75 h / -78 - 0 °C / Inert atmosphere 1.2: 0.25 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 0 - 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 0.5 h / -78 °C 1.2: 0.33 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.17 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: n-butyllithium / ethanol; tetrahydrofuran / 0.5 h / -72 °C / Inert atmosphere 1.2: 1 h / 20 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 20 °C |
Multi-step reaction with 2 steps 1: N-fluorobis(benzenesulfon)imide; sec.-butyllithium / tetrahydrofuran / -78 °C 2: tetrabutyl ammonium fluoride / tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C 3.1: nitric acid / 0.5 h / 0 °C 4.1: hydrogenchloride; tin(ll) chloride / 0 - 20 °C 4.2: pH 7 5.1: bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; triethylamine / dichloromethane / 24 h / 20 °C 5.2: 0.5 h 6.1: butan-1-ol / 24 h / 160 °C 7.1: dmap; triethylamine / dichloromethane / 23 h / 20 °C 8.1: potassium phosphate; tricyclohexylphosphine / palladium diacetate / water; toluene / 22 h / 80 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 9 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C 3.1: nitric acid / 0.5 h / 0 °C 4.1: hydrogenchloride; tin(ll) chloride / 0 - 20 °C 4.2: pH 7 5.1: bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; triethylamine / dichloromethane / 24 h / 20 °C 5.2: 0.5 h 6.1: butan-1-ol / 24 h / 160 °C 7.1: dmap; triethylamine / dichloromethane / 23 h / 20 °C 8.1: potassium phosphate; tricyclohexylphosphine / palladium diacetate / water; toluene / 22 h / 80 °C 9.1: trifluoroacetic acid / 0.83 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | To a suspension of sodium hydride (60% dispersion in mineral oil, 2.14 g, 53.5 mmol) in dry N,N-dimethylformamide (30 mL) was added a solution of <strong>[640735-23-5]4-fluoro-1H-pyrrolo[2,3-b]pyridine</strong> (5.77 g, 42.46 mmol) in dry N,N-dimethylformamide (58 mL) dropwise at 0 C. The mixture was stirred at 0 C for 15 min. To the mixture was added a solution of triisopropylsilyl chloride (10 mL, 46.71 mmol) in dry N,N-dimethylformamide (12 mL) dropwise at 0 C over 30 min. The reaction mixture was allowed to warm to room temperature and the mixture was stirred at room temperature for 42 h. The reaction mixture was poured into ice water (800 mL) and the mixture was extracted with dichloromethane (4 x 200 mL). The combined organic layers were washed with water (2 x 200 mL), dried over sodium sulfate, filtered and evaporated. The residue was purified by gradient silica gel column chromatography eluting with n-heptane:ethyl acetate (100:0 to 50:50) to afford the title compound (8.51 g, 29.14 mmol, 68%) as a pale yellow liquid. LCMS Method A: 99%, tR=2.242 min, m/z = 293.2 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 1 h / -78 °C / Inert atmosphere 1.2: 1.25 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1.1: N-fluorobis(benzenesulfon)imide; sec.-butyllithium / tetrahydrofuran / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane; tetrahydrofuran / 12 h / 0 - 15 °C 4.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 12 h / 0 - 10 °C 5.1: sodium hydroxide / tetrahydrofuran / 12 h / 10 °C 6.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 7.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -78 °C / Inert atmosphere 7.2: 0.5 h / -78 °C 8.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 100 °C / Inert atmosphere 9.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 10.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 12 h / 25 °C | ||
Multi-step reaction with 11 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 10 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 12 h / 25 °C 3.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 1 h / 50 °C 4.1: sodium hydroxide / 1,1,2,2-tetrachloroethylene / 2 h / 25 °C 5.1: sodium hydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 6.1: sec.-butyllithium / tetrahydrofuran; hexane / 0.5 h / -78 °C 6.2: 1.5 h / -78 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 8.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 9.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 110 °C / Inert atmosphere 10.1: lithium diisopropyl amide / tetrahydrofuran / 1.5 h / -78 °C / Inert atmosphere 10.2: 10.5 h / 10 °C 11.1: tetrahydrofuran / 12 h / 80 °C | ||
Multi-step reaction with 12 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 10 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 12 h / 25 °C 3.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 1 h / 50 °C 4.1: sodium hydroxide / 1,1,2,2-tetrachloroethylene / 2 h / 25 °C 5.1: sodium hydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 6.1: sec.-butyllithium / tetrahydrofuran; hexane / 0.5 h / -78 °C 6.2: 1.5 h / -78 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 8.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 9.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -78 °C / Inert atmosphere 9.2: 0.5 h / -78 °C 10.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 100 °C / Inert atmosphere 11.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 12.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 12 h / 25 °C |
Multi-step reaction with 9 steps 1.1: N-fluorobis(benzenesulfon)imide; sec.-butyllithium / tetrahydrofuran / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane; tetrahydrofuran / 12 h / 0 - 15 °C 4.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 12 h / 0 - 10 °C 5.1: sodium hydroxide / tetrahydrofuran / 12 h / 10 °C 6.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 7.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 110 °C / Inert atmosphere 8.1: lithium diisopropyl amide / tetrahydrofuran / 1.5 h / -78 °C / Inert atmosphere 8.2: 10.5 h / 10 °C 9.1: tetrahydrofuran / 12 h / 80 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1.1: N-fluorobis(benzenesulfon)imide; sec.-butyllithium / tetrahydrofuran / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane; tetrahydrofuran / 12 h / 0 - 15 °C 4.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 12 h / 0 - 10 °C 5.1: sodium hydroxide / tetrahydrofuran / 12 h / 10 °C 6.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 7.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 110 °C / Inert atmosphere 8.1: lithium diisopropyl amide / tetrahydrofuran / 1.5 h / -78 °C / Inert atmosphere 8.2: 10.5 h / 10 °C 9.1: tetrahydrofuran / 12 h / 80 °C 10.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 0.5 h / 30 °C 10.2: 11.5 h / 30 °C | ||
Multi-step reaction with 11 steps 1.1: N-fluorobis(benzenesulfon)imide; sec.-butyllithium / tetrahydrofuran / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane; tetrahydrofuran / 12 h / 0 - 15 °C 4.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 12 h / 0 - 10 °C 5.1: sodium hydroxide / tetrahydrofuran / 12 h / 10 °C 6.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 7.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -78 °C / Inert atmosphere 7.2: 0.5 h / -78 °C 8.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 100 °C / Inert atmosphere 9.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 10.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 12 h / 25 °C 11.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 0.5 h / 30 °C 11.2: 11.5 h / 30 °C | ||
Multi-step reaction with 12 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 10 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 12 h / 25 °C 3.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 1 h / 50 °C 4.1: sodium hydroxide / 1,1,2,2-tetrachloroethylene / 2 h / 25 °C 5.1: sodium hydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 6.1: sec.-butyllithium / tetrahydrofuran; hexane / 0.5 h / -78 °C 6.2: 1.5 h / -78 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 8.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 9.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 110 °C / Inert atmosphere 10.1: lithium diisopropyl amide / tetrahydrofuran / 1.5 h / -78 °C / Inert atmosphere 10.2: 10.5 h / 10 °C 11.1: tetrahydrofuran / 12 h / 80 °C 12.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 0.5 h / 30 °C 12.2: 11.5 h / 30 °C |
Multi-step reaction with 13 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 10 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 12 h / 25 °C 3.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 1 h / 50 °C 4.1: sodium hydroxide / 1,1,2,2-tetrachloroethylene / 2 h / 25 °C 5.1: sodium hydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 6.1: sec.-butyllithium / tetrahydrofuran; hexane / 0.5 h / -78 °C 6.2: 1.5 h / -78 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 8.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 9.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -78 °C / Inert atmosphere 9.2: 0.5 h / -78 °C 10.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 100 °C / Inert atmosphere 11.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 12.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 12 h / 25 °C 13.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 0.5 h / 30 °C 13.2: 11.5 h / 30 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1.1: N-fluorobis(benzenesulfon)imide; sec.-butyllithium / tetrahydrofuran / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane; tetrahydrofuran / 12 h / 0 - 15 °C 4.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 12 h / 0 - 10 °C 5.1: sodium hydroxide / tetrahydrofuran / 12 h / 10 °C 6.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 7.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 110 °C / Inert atmosphere 8.1: lithium diisopropyl amide / tetrahydrofuran / 1.5 h / -78 °C / Inert atmosphere 8.2: 10.5 h / 10 °C 9.1: tetrahydrofuran / 12 h / 80 °C 10.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 0.5 h / 30 °C 10.2: 11.5 h / 30 °C | ||
Multi-step reaction with 11 steps 1.1: N-fluorobis(benzenesulfon)imide; sec.-butyllithium / tetrahydrofuran / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane; tetrahydrofuran / 12 h / 0 - 15 °C 4.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 12 h / 0 - 10 °C 5.1: sodium hydroxide / tetrahydrofuran / 12 h / 10 °C 6.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 7.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -78 °C / Inert atmosphere 7.2: 0.5 h / -78 °C 8.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 100 °C / Inert atmosphere 9.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 10.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 12 h / 25 °C 11.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 0.5 h / 30 °C 11.2: 11.5 h / 30 °C | ||
Multi-step reaction with 12 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 10 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 12 h / 25 °C 3.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 1 h / 50 °C 4.1: sodium hydroxide / 1,1,2,2-tetrachloroethylene / 2 h / 25 °C 5.1: sodium hydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 6.1: sec.-butyllithium / tetrahydrofuran; hexane / 0.5 h / -78 °C 6.2: 1.5 h / -78 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 8.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 9.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 110 °C / Inert atmosphere 10.1: lithium diisopropyl amide / tetrahydrofuran / 1.5 h / -78 °C / Inert atmosphere 10.2: 10.5 h / 10 °C 11.1: tetrahydrofuran / 12 h / 80 °C 12.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 0.5 h / 30 °C 12.2: 11.5 h / 30 °C |
Multi-step reaction with 13 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 10 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 12 h / 25 °C 3.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 1 h / 50 °C 4.1: sodium hydroxide / 1,1,2,2-tetrachloroethylene / 2 h / 25 °C 5.1: sodium hydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 6.1: sec.-butyllithium / tetrahydrofuran; hexane / 0.5 h / -78 °C 6.2: 1.5 h / -78 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 8.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 9.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -78 °C / Inert atmosphere 9.2: 0.5 h / -78 °C 10.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 100 °C / Inert atmosphere 11.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 12.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 12 h / 25 °C 13.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 0.5 h / 30 °C 13.2: 11.5 h / 30 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1.1: hexachloroethane; sec.-butyllithium / tetrahydrofuran / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 12 h / 0 - 30 °C 4.1: methyl chloroformate; 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 24 h / 30 °C / Inert atmosphere 5.1: sodium hydride / tetrahydrofuran / 12 h / 25 °C / Inert atmosphere 6.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -60 °C / Inert atmosphere 6.2: 0.5 h / -60 °C 7.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 100 °C / Inert atmosphere 8.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 9.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 12 h / 30 °C 10.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 0.5 h / 25 °C 10.2: 0.5 h / 25 °C | ||
Multi-step reaction with 12 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 10 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 12 h / 25 °C 3.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 1 h / 50 °C 4.1: sodium hydroxide / 1,1,2,2-tetrachloroethylene / 2 h / 25 °C 5.1: sodium hydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 6.1: sec.-butyllithium / tetrahydrofuran; hexane / 0.5 h / -60 °C / Inert atmosphere 6.2: 0.5 h / -60 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 8.1: sodium hydride / tetrahydrofuran / 12 h / 25 °C / Inert atmosphere 9.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,2-dimethoxyethane; water / 12 h / 120 °C 10.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 10.2: 0.5 h / -78 °C 11.1: sodium hydroxide; water / tetrahydrofuran / 3 h / 75 °C 12.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 0.5 h / 25 °C 12.2: 0.5 h / 25 °C | ||
Multi-step reaction with 13 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 10 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 12 h / 25 °C 3.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 1 h / 50 °C 4.1: sodium hydroxide / 1,1,2,2-tetrachloroethylene / 2 h / 25 °C 5.1: sodium hydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 6.1: sec.-butyllithium / tetrahydrofuran; hexane / 0.5 h / -60 °C / Inert atmosphere 6.2: 0.5 h / -60 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 8.1: sodium hydride / tetrahydrofuran / 12 h / 25 °C / Inert atmosphere 9.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -60 °C / Inert atmosphere 9.2: 0.5 h / -60 °C 10.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 100 °C / Inert atmosphere 11.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 12.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 12 h / 30 °C 13.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 0.5 h / 25 °C 13.2: 0.5 h / 25 °C |
Multi-step reaction with 9 steps 1.1: hexachloroethane; sec.-butyllithium / tetrahydrofuran / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 12 h / 0 - 30 °C 4.1: methyl chloroformate; 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 24 h / 30 °C / Inert atmosphere 5.1: sodium hydride / tetrahydrofuran / 12 h / 25 °C / Inert atmosphere 6.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,2-dimethoxyethane; water / 12 h / 120 °C 7.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 7.2: 0.5 h / -78 °C 8.1: sodium hydroxide; water / tetrahydrofuran / 3 h / 75 °C 9.1: 1,1'-carbonyldiimidazole / N,N-dimethyl-formamide / 0.5 h / 25 °C 9.2: 0.5 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1.1: hexachloroethane; sec.-butyllithium / tetrahydrofuran / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 12 h / 0 - 30 °C 4.1: methyl chloroformate; 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 24 h / 30 °C / Inert atmosphere 5.1: sodium hydride / tetrahydrofuran / 12 h / 25 °C / Inert atmosphere 6.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -60 °C / Inert atmosphere 6.2: 0.5 h / -60 °C 7.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 100 °C / Inert atmosphere 8.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 9.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 12 h / 30 °C 10.1: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 2 h / 30 °C | ||
Multi-step reaction with 12 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 10 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 12 h / 25 °C 3.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 1 h / 50 °C 4.1: sodium hydroxide / 1,1,2,2-tetrachloroethylene / 2 h / 25 °C 5.1: sodium hydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 6.1: sec.-butyllithium / tetrahydrofuran; hexane / 0.5 h / -60 °C / Inert atmosphere 6.2: 0.5 h / -60 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 8.1: sodium hydride / tetrahydrofuran / 12 h / 25 °C / Inert atmosphere 9.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,2-dimethoxyethane; water / 12 h / 120 °C 10.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 10.2: 0.5 h / -78 °C 11.1: sodium hydroxide; water / tetrahydrofuran / 3 h / 75 °C 12.1: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 2 h / 30 °C | ||
Multi-step reaction with 13 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 10 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 12 h / 25 °C 3.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 1 h / 50 °C 4.1: sodium hydroxide / 1,1,2,2-tetrachloroethylene / 2 h / 25 °C 5.1: sodium hydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 6.1: sec.-butyllithium / tetrahydrofuran; hexane / 0.5 h / -60 °C / Inert atmosphere 6.2: 0.5 h / -60 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 8.1: sodium hydride / tetrahydrofuran / 12 h / 25 °C / Inert atmosphere 9.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -60 °C / Inert atmosphere 9.2: 0.5 h / -60 °C 10.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 100 °C / Inert atmosphere 11.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 12.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 12 h / 30 °C 13.1: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 2 h / 30 °C |
Multi-step reaction with 9 steps 1.1: hexachloroethane; sec.-butyllithium / tetrahydrofuran / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 12 h / 0 - 30 °C 4.1: methyl chloroformate; 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 24 h / 30 °C / Inert atmosphere 5.1: sodium hydride / tetrahydrofuran / 12 h / 25 °C / Inert atmosphere 6.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,2-dimethoxyethane; water / 12 h / 120 °C 7.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 7.2: 0.5 h / -78 °C 8.1: sodium hydroxide; water / tetrahydrofuran / 3 h / 75 °C 9.1: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 2 h / 30 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 10 steps 1.1: hexachloroethane; sec.-butyllithium / tetrahydrofuran / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 12 h / 0 - 30 °C 4.1: methyl chloroformate; 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 24 h / 30 °C / Inert atmosphere 5.1: sodium hydride / tetrahydrofuran / 12 h / 25 °C / Inert atmosphere 6.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -60 °C / Inert atmosphere 6.2: 0.5 h / -60 °C 7.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 100 °C / Inert atmosphere 8.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 9.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 12 h / 30 °C 10.1: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 2 h / 25 °C | ||
Multi-step reaction with 12 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 10 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 12 h / 25 °C 3.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 1 h / 50 °C 4.1: sodium hydroxide / 1,1,2,2-tetrachloroethylene / 2 h / 25 °C 5.1: sodium hydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 6.1: sec.-butyllithium / tetrahydrofuran; hexane / 0.5 h / -60 °C / Inert atmosphere 6.2: 0.5 h / -60 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 8.1: sodium hydride / tetrahydrofuran / 12 h / 25 °C / Inert atmosphere 9.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,2-dimethoxyethane; water / 12 h / 120 °C 10.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 10.2: 0.5 h / -78 °C 11.1: sodium hydroxide; water / tetrahydrofuran / 3 h / 75 °C 12.1: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 2 h / 25 °C | ||
Multi-step reaction with 13 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 10 °C 2.1: 3-chloro-benzenecarboperoxoic acid / tetrahydrofuran / 12 h / 25 °C 3.1: 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 1 h / 50 °C 4.1: sodium hydroxide / 1,1,2,2-tetrachloroethylene / 2 h / 25 °C 5.1: sodium hydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 6.1: sec.-butyllithium / tetrahydrofuran; hexane / 0.5 h / -60 °C / Inert atmosphere 6.2: 0.5 h / -60 °C 7.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 8.1: sodium hydride / tetrahydrofuran / 12 h / 25 °C / Inert atmosphere 9.1: lithium diisopropyl amide / tetrahydrofuran / 0.17 h / -60 °C / Inert atmosphere 9.2: 0.5 h / -60 °C 10.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate / 1,2-dimethoxyethane / 12 h / 100 °C / Inert atmosphere 11.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.5 h / 25 °C 12.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 12 h / 30 °C 13.1: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 2 h / 25 °C |
Multi-step reaction with 9 steps 1.1: hexachloroethane; sec.-butyllithium / tetrahydrofuran / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 12 h / 0 - 30 °C 4.1: methyl chloroformate; 1,1,1,3,3,3-hexamethyl-disilazane / tetrahydrofuran / 24 h / 30 °C / Inert atmosphere 5.1: sodium hydride / tetrahydrofuran / 12 h / 25 °C / Inert atmosphere 6.1: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,2-dimethoxyethane; water / 12 h / 120 °C 7.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 7.2: 0.5 h / -78 °C 8.1: sodium hydroxide; water / tetrahydrofuran / 3 h / 75 °C 9.1: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 2 h / 25 °C |
Tags: 640735-25-7 synthesis path| 640735-25-7 SDS| 640735-25-7 COA| 640735-25-7 purity| 640735-25-7 application| 640735-25-7 NMR| 640735-25-7 COA| 640735-25-7 structure
[ 868387-37-5 ]
5-Fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine
Similarity: 0.93
[ 1093759-49-9 ]
1-[Tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridine
Similarity: 0.87
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H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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