methoxy(trimethyl)silane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 500 ml 5-neck round-bottom flask, rendered inert with nitrogen and equipped with paddle stirrer, dropping funnel, thermometer, and water separator with reflux condenser, is charged with 70 g (0.5 mol) of methyl-trimethoxysilane (available commercially from Wacker Chemie AG), 6 g (0.05 mol) of trimethylmethoxysilane (prepared in the laboratory by reacting trimethyl-chlorosilane with methanol), and 98.6 g of Isopar E (isoparaffinic hydrocarbon mixture having a boiling range of 113-143° C., available commercially from ExxonMobil). The water separator is filled to the brim with Isopar E. Accompanied by stirring at 300 rpm, a solution of 40.5 g of 50% strength aqueous potassium hydroxide solution (0.36 mol of potassium hydroxide) and 3.2 g of demineralized water is metered in over 6 minutes. During this metered addition, the mixture heats up to 63° C. The mixture is heated to boiling temperature (70° C.). The distillate separates out as the bottom phase in the water separator. Up to a boiling temperature of 118° C., 60.3 g of colorless, slightly turbid distillate are accumulated, and—according to analysis by gas chromatography—contains 84 area % of methanol, 10.8 area % of water, 3.3 area % of Isopar E, and 0.8 area % of trimethylmethoxysilane. The suspension which remains is subsequently evaporated to dryness with stirring under a full oil-pump vacuum (5 hPa) to 70° C. This gives 55.9 g of fine, white, free-flowable powder with a solids content of 99.9% (determined using the HR73 halogen moisture analyzer from Mettler Toledo at 160° C.). A 50% strength aqueous solution prepared with this powder exhibits no precipitation even after being stored at room temperature for two weeks in the absence of air. A 500 ml 5-neck round-bottom flask, rendered inert with nitrogen equipped with paddle stirrer with reflux condenser prepared in the laboratory is metered in over 6 minutes During this metered addition heats up to 63° C The suspension which remains is subsequently evaporated to dryness with stirring under a full oil-pump vacuum (5 hPa) to 70° C at 160° C. A 50% strength aqueous solution prepared with this powder no precipitation even after being stored at room temperature for two weeks in the absence of air

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-[2-hydroxy-4-(1-triisopropylsilanyl-1H-pyrrol-3-yl)-phenyl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one in MeCN (10 mL) is added HF-Pyridine (0.2 mL, 2.23 mmol) and the reaction mixture is stirred at RT for 2 h. TMSOMe (5 mL) is added to consume unreacted HF, and the crude reaction mixture is concentrated in vacuo. The residue is purified by reverse phase MPLC using 1-40% MeCN/H2O as eluent to give the title compound: (M−1)−=292. to consume unreacted HF the crude reaction mixture is concentrated in vacuo The residue is purified by reverse phase MPLC

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 6-aminoisoquinolin-1-ol in DMF was added methoxytrimethylsilane and (R)-tert-butyl 2-fluoro-2 oxo-1-(thiophen-3-yl)ethylcarbamate and the solution was stirred at room temperature for 6 h. The mixture was poured into EtOAc, washed with NH4Cl(sat)/HCl (1N) followed by NaHCO3 (0.05%), dried (Na2SO4), filtered and evaporated. Column chromatography (SiO2, 5% MeOH, CH2Cl2) gave pure (R)-tert-butyl 2-(1-hydroxyisoquinolin-6-ylamino)-2-oxo-1-(thiophen-3-yl)ethylcarbamate) (91.8% ee by Chiracel OD-RH). washed with NH4Cl(sat)/HCl (1N) dried (Na2SO4) filtered evaporated

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 500 ml 5-neck round-bottom flask, rendered inert with nitrogen and equipped with paddle stirrer, dropping funnel, thermometer, and water separator with reflux condenser, is charged with 70 g (0.5 mol) of methyl-trimethoxysilane (available commercially from Wacker Chemie AG), 6 g (0.05 mol) of trimethylmethoxysilane (prepared in the laboratory by reacting trimethyl-chlorosilane with methanol), and 98.6 g of Isopar E (isoparaffinic hydrocarbon mixture having a boiling range of 113-143° C., available commercially from ExxonMobil). The water separator is filled to the brim with Isopar E. Accompanied by stirring at 300 rpm, a solution of 40.5 g of 50% strength aqueous potassium hydroxide solution (0.36 mol of potassium hydroxide) and 3.2 g of demineralized water is metered in over 6 minutes. During this metered addition, the mixture heats up to 63° C. The mixture is heated to boiling temperature (70° C.). The distillate separates out as the bottom phase in the water separator. Up to a boiling temperature of 118° C., 60.3 g of colorless, slightly turbid distillate are accumulated, and—according to analysis by gas chromatography—contains 84 area % of methanol, 10.8 area % of water, 3.3 area % of Isopar E, and 0.8 area % of trimethylmethoxysilane. The suspension which remains is subsequently evaporated to dryness with stirring under a full oil-pump vacuum (5 hPa) to 70° C. This gives 55.9 g of fine, white, free-flowable powder with a solids content of 99.9% (determined using the HR73 halogen moisture analyzer from Mettler Toledo at 160° C.). A 50% strength aqueous solution prepared with this powder exhibits no precipitation even after being stored at room temperature for two weeks in the absence of air. A 500 ml 5-neck round-bottom flask, rendered inert with nitrogen equipped with paddle stirrer with reflux condenser prepared in the laboratory is metered in over 6 minutes During this metered addition heats up to 63° C The suspension which remains is subsequently evaporated to dryness with stirring under a full oil-pump vacuum (5 hPa) to 70° C at 160° C. A 50% strength aqueous solution prepared with this powder no precipitation even after being stored at room temperature for two weeks in the absence of air

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: B(OCH3)3 (20.0 g, 0.19 mol) and KCN (12.5 g, 0.19 mol) were dissolved in TMSCN (66.8 g, 0.67 mol) and heated at a reflux temperature of 70° C. under protective gas for 18 hours. After cooling, all volatile components (unreacted TMSCN, formed TMSOMe) were distilled off to give powdery K[B(CN)3(OCH3)] in a yield of 27.8 g (92%). After cooling

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 6-aminoisoquinolin-1-ol in DMF was added methoxytrimethylsilane and (R)-tert-butyl 2-fluoro-2 oxo-1-(thiophen-3-yl)ethylcarbamate and the solution was stirred at room temperature for 6 h. The mixture was poured into EtOAc, washed with NH4Cl (sat)/HCl (1N) followed by NaHCO3 (0.05%), dried (Na2SO4), filtered and evaporated. Column chromatography (SiO2, 5% MeOH, CH2Cl2) gave pure (R)-tert-butyl 2-(1-hydroxyisoquinolin-6-ylamino)-2-oxo-1-(thiophen-3-yl)ethylcarbamate) (91.8% ee by Chiracel OD-RH). washed with NH4Cl (sat)/HCl (1N) dried (Na2SO4) filtered evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of Example 52B (1.26 g, 5.22 mmol) in CH2Cl2 (5 mL) was cooled to −78° C. after which the starting material was observed to precipitate. Methoxytrimethylsilane (1.44 mL, 10.5 mmol) and trimethylsilyltrifluoromethane sulfonate (0.047 mL, 0.261 mmol) were added and the reaction mixture was allowed to proceed for 24 hr with gradual warming to ambient temperature. The reaction was quenched with saturated aq NaHCO3 solution (10 mL), then diluted with EtOAc (50 mL) and H2O (30 mL). The separated aqueous phase was extracted with EtOAc, and the combined organic extract was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The result was 1.42 g (95%) of the title compound as a yellow oil. 1H NMR (300 MHz, DMSO-d6) δ 8.53 (s, 1H), 7.98 (d, J=8.7, 2H), 7.87 (d, J=8.4, 2H), 5.55 (s, 1H), 3.34 (s, 6H). MS (DCI+) m/z 288 (M+H). to precipitate The reaction was quenched with saturated aq NaHCO3 solution (10 mL) diluted with EtOAc (50 mL) and H2O (30 mL) The separated aqueous phase was extracted with EtOAc the combined organic extract was washed with brine dried (Na2SO4) filtered concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methoxytrimethylsilane (545 mg, 5.23 mmol) and trimethylsilyl trifluoromethanesulfonate (30 mg, 0.13 mmol) were added to a solution of 2-(4-fluorophenyl)oxazole-4-carbaldehyde (500 mg, 2.62 mmol) in dry CH2Cl2 (2 mL) at −78° C. The reaction mixture was allowed to warm up to room temperature and stirred for 24 h, quenched with saturated aqueous NaHCO3 solution, and the crude product was extracted with EtOAc. The organic layer was washed with 10% NaHCO3 solution, water and brine and dried over anhydrous sodium sulfate. Solvent was removed under reduced pressure to get 4-(dimethoxymethyl)-2-(4-fluorophenyl)oxazole (400 mg, crude), which was carried through without further purification. 1H NMR (400 MHz, CDCl3) δ 8.08-8.05 (m, 2H), 7.71 (d, J=1.2 Hz, 1H), 7.16-7.12 (m, 2H), 5.50 (d, J=0.9 Hz, 1H), 3.41 (s, 6H). MS (ESI) m/z: Calculated for C12H12FNO3: 237.08. found: 259.9 (M+Na)+. quenched with saturated aqueous NaHCO3 solution the crude product was extracted with EtOAc The organic layer was washed with 10% NaHCO3 solution, water and brine dried over anhydrous sodium sulfate Solvent was removed under reduced pressure

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 6-chloro-4-(5,6-dimethoxypyridin-2-ylamino)pyridazine-3-carboxamide (500 mg, 1.6 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (692 mg, 3.2 mmol) in NMP (1.5 mL), methoxy trimethylsilane (0.5 mL, 3.6 mmol) was added and the mixture heated to 150° C. for 65 h. The mixture was concentrated under high vacuum to obtain a sticky crude mass that was purified by chromatography (silica, 100-200 mesh, 1-10% methanol in dichloromethane) to give 6-((1R,2S)-2-amino-cyclohexylamino)-4-(5,6-dimethoxy-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide (220 mg 35%) as a yellow solid. LC-MS 388 [M+H]+. The mixture was concentrated under high vacuum to obtain a sticky crude mass that was purified by chromatography (silica, 100-200 mesh, 1-10% methanol in dichloromethane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 6-aminoisoquinolin-1-ol in DMF was added methoxytrimethylsilane and (R)-tert-butyl 2-fluoro-2 oxo-1-(thiophen-3-yl)ethylcarbamate and the solution was stirred at room temperature for 6 h. The mixture was poured into EtOAc, washed with NH4Cl (sat)/HCl (1N) followed by NaHCO3 (0.05%), dried (Na2SO4), filtered and evaporated. Column chromatography (SiO2, 5% MeOH, CH2Cl2) gave pure (R)-tert-butyl 2-(1-hydroxyisoquinolin-6-ylamino)-2-oxo-1-(thiophen-3-yl)ethylcarbamate) (91.8% ee by Chiracel OD-RH). washed with NH4Cl (sat)/HCl (1N) dried (Na2SO4) filtered evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 0.1 mole 12-isocyanatododecanoic acid chloride was reacted as in Example 1 with 0.11 mole methoxytrimethyl silane at 75° C. until the acid chloride band at 1800 cm-1 had disappeared. The desired product was obtained after distillation.