tetramethoxymethane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tetramethyl orthocarbonate (1.24 mL, 9.3 mmol) was added to a suspension of 2-chloroquinoline-3,4-diamine, see U.S. Pat. No. 5,756,747 (Gerster) Example 30, (1.5 g, 7.75 mmol) in acetic acid (8 mL), and the reaction was stirred overnight at room temperature. An analysis by LC/MS indicated the reaction was incomplete, and additional tetramethyl orthocarbonate (0.5 equivalent) was added. The reaction was stirred overnight at room temperature and diluted with water (100 mL). The mixture was adjusted to pH 7 with the addition of 2 N aqueous sodium hydroxide. Dichloromethane (100 mL) was added to the mixture, and a precipitate formed. The precipitate was isolated by filtration to provide 1.13 g of 4-chloro-2-methoxy-1H-imidazo[4,5-c]quinoline as a gray solid. a precipitate formed The precipitate was isolated by filtration

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2,3-diamino-4-methoxybenzoate [0.5 g, Reference Example 8(a)] acetic acid (0.15 ml) and tetramethoxymethane (0.53 ml) was stirred at 80° C. for 40 minutes. After cooling to room temperature the reaction mixture was diluted with a mixture of methanol (3.6 ml), 1N sodium hydroxide (2.55 ml) and water (8 ml). The resulting precipitate was filtered and then passed through a short filtration silica gel column to give the title compound (0.49 g) as a tan coloured solid. M+236. NMR (CDCl3): δ 3.93(s, 3H), 4.05(s, 3H), 4.23(s, 3H), 6.69(d, J=8 Hz, 1H), 7.74(d, J=8 Hz, 1H), 9.48(bs, 1H)]. After cooling to room temperature the reaction mixture The resulting precipitate was filtered passed through a short filtration silica gel column

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tetramethyl orthocarbonate (1.24 mL, 9.3 mmol) was added to a suspension of 2-chloroquinoline-3,4-diamine, see U.S. Pat. No. 5,756,747 (Gerster) Example 30, (1.5 g, 7.75 mmol) in acetic acid (8 mL), and the reaction was stirred overnight at room temperature. An analysis by LC/MS indicated the reaction was incomplete, and additional tetramethyl orthocarbonate (0.5 equivalent) was added. The reaction was stirred overnight at room temperature and diluted with water (100 mL). The mixture was adjusted to pH 7 with the addition of 2 N aqueous sodium hydroxide. Dichloromethane (100 mL) was added to the mixture, and a precipitate formed. The precipitate was isolated by filtration to provide 1.13 g of 4-chloro-2-methoxy-1H-imidazo[4,5-c]quinoline as a gray solid. a precipitate formed The precipitate was isolated by filtration

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2,3-diamino-4-methoxybenzoate [0.5 g, Reference Example 8(a)] acetic acid (0.15 ml) and tetramethoxymethane (0.53 ml) was stirred at 80° C. for 40 minutes. After cooling to room temperature the reaction mixture was diluted with a mixture of methanol (3.6 ml), 1N sodium hydroxide (2.55 ml) and water (8 ml). The resulting precipitate was filtered and then passed through a short filtration silica gel column to give the title compound (0.49 g) as a tan coloured solid. M+236. NMR (CDCl3): δ 3.93(s,3H), 4.05(s,3H), 4.23(s,3H), 6.69(d,J=8 Hz,1H), 7.74(d,J=8 Hz,1H). 9.48(bs,1H)] After cooling to room temperature the reaction mixture The resulting precipitate was filtered passed through a short filtration silica gel column

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-[3-[N-[(E)-3-(6-acetamidopyridin-3-yl)acryloylglycyl]-N-methylamino]-2,6-dichlorobenzyloxy]-2-aminoaniline (735 mg) in acetic acid (7.4 ml) was added tetramethyl orthocarbonate (215 mg) at ambient temperature, and the mixture was stirred for 8 hours at the same temperature. The solvent was removed, and the residue was dissolved in chloroform. The solution was washed with saturated sodium bicarbonate solution, water and brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (chloroform-methanol) to give 4-[3-[N-[(E)-3-(6-acetamidopyridin-3-yl)acryloylglycyl]-N-methylamino]-2,6-dichlorobenzyloxy]-2-methoxy-1H-benzimidazole (654 mg). The solvent was removed the residue was dissolved in chloroform The solution was washed with saturated sodium bicarbonate solution, water and brine dried over magnesium sulfate concentrated in vacuo The residue was purified by flash chromatography (chloroform-methanol)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-[2-(6-Amino-7-hydroxy-2,3-dihydro-1H-inden-1-yl)ethyl]acetamide hydrochloride (100 mg, 0.369 mmol) and tetramethoxymethane (151 mg, 1.11 mmol) were heated under reflux in tetrahydrofuran (3.7 mL) for 2 hr. The reaction solution was diluted with ethyl acetate and saturated aqueous sodium hydrogencarbonate solution, washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→95/5) to give the title compound (58.4 mg, yield 58%). washed with saturated brine dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→95/5)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Hydroxy-2-methyl-1-[4-(2-morpholin-4-ylethyl)phenyl]propane-1-sulfonamide (44 mg) was stirred with tetramethyl orthocarbonate (1 ml) and glacial acetic acid (0.2 ml) at 80° C. for 17 hours. The solvents were removed under reduced pressure. This gave the crude product with a molecular weight of 382.5 g/mol (C18H26N2O5S), which was used without further purification. The solvents were removed under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Hydroxy-2-methyl-1-(4-morpholin-4-ylmethylphenyl)propane-1-sulfonamide (350 mg) was stirred with tetramethyl orthocarbonate (5 ml) and glacial acetic acid (1 ml) at 80° C. for 16 hours. The solvents were removed under reduced pressure and the residue was used further without further purification. The solvents were removed under reduced pressure the residue was used further without further purification

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Hydroxy-2-methyl-1-(4-morpholin-4-ylphenyl)propane-1-sulfonamide (41 mg) was stirred with tetramethyl orthocarbonate (0.2 ml), glacial acetic acid (0.01 ml) and dioxane (0.1 ml) at 90° C. for 4 hours. The solvents were removed under reduced pressure and the residue was used further without further purification. The solvents were removed under reduced pressure the residue was used further without further purification

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 2.01 g of 2-(4-bromophenyl)-3-hydroxy-3-methylbutane-2-sulfonamide in 15 ml of tetramethoxymethane was admixed with 3 ml of acetic acid and stirred at 100° C. for 1.5 hours. After the removal of the solvent under reduced pressure, the crude product was purified by means of normal phase chromatography using a Flashmaster with an n-heptane/ethyl acetate gradient. The product-containing fractions were combined, concentrated by rotary evaporation and dried under high vacuum. This gave the product (0.21 g) with a molecular weight of 362.2 g/mol (C13H16BrNO4S). After the removal of the solvent under reduced pressure the crude product was purified by means of normal phase chromatography concentrated by rotary evaporation dried under high vacuum