dimethylphosphorylmethanamine

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

Procedure: A solution of 4.95 g (3,5-Dichloro-2-pyridyloxy)-3,4-dinitrobenzene in 15 ml of toluene is refluxed, and 3.21 g of melted P,P-dimethyl-aminomethylphosphine oxide are added. After the initial evolution of nitrous gases has finished, the mixture is refluxed for a further 2 hours. The brown solution is subsequently concentrated by evaporation, and the residue is recrystallised from 20 ml of ethyl acetate and 100 ml of ether. There are obtained, in the form of yellow crystals, 4.9 g (84% of theory) of N-[2-nitro-5-(3,5-dichloro-2-pyridyloxy)-phenyl]-P,P-dimethyl-aminomethylphosphine oxide, m.p. 153°-155° C. the mixture is refluxed for a further 2 hours The brown solution is subsequently concentrated by evaporation the residue is recrystallised from 20 ml of ethyl acetate and 100 ml of ether

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

Procedure: A solution of 4.97 g of (5-trifluoromethyl-2-pyridyloxy)-3,4-dinitrobenzene in 15 ml of toluene is refluxed, and 3.21 g of melted P,P-dimethyl-aminomethylphosphine oxide are added dropwise. The mixture is refluxed for a further 2 hours, nitrous gases being evolved at the start. The brown solution is subsequently concentrated by evaporation, and the residue is recrystallised from 50 ml of ethyl acetate to thus obtain 4.10 g (70% of theory) of N-[2-nitro-5-(5-trifluoromethyl-2-pyridyloxy)-phenyl]-P,P-dimethyl-aminomethylphosphine oxide in the form of yellow crystals, m.p. 158°-160° C. The mixture is refluxed for a further 2 hours The brown solution is subsequently concentrated by evaporation the residue is recrystallised from 50 ml of ethyl acetate to thus obtain 4.10 g (70% of theory) of N-[2-nitro-5-(5-trifluoromethyl-2-pyridyloxy)-phenyl]-P,P-dimethyl-aminomethylphosphine oxide in the form of yellow crystals, m.p. 158°-160° C.

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

Procedure: 5-(4-(4-(3-fluorobenzyloxy)-3-chlorophenylamino)quinazolin-6-yl)furan-2-carbaldehyde (compound 1.7) and (dimethylphosphinoyl)methanamine (preparation: Maier, Ludwig Phosphorus, Sulfur and Silicon and the Related Elements, 53(1-4), 43-67; 1990) were suspended in dichloromethane (20 mL). Sequentially, acetic acid (3 drops) and sodium triacetoxyborohydride (2 equiv.) were added at room temperature. The mixture was stirred at room temperature until the starting material disappeared. The reaction was quenched with 2N NaOH aqueous solution and extracted with dichloromethane. The combined organic layer and extracts were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography, eluting with 20% methanol in dichloromethane to give the desired product as yellow crystalline solid. LCMS ESI(+) m/z: 566 (M+1). 1H NMR (300 MHz, CD3OD) δ 8.65 (s, 1H), 8.46 (s, 1H), 8.15 (m, 1H), 7.91 (d, 1H), 7.75 (m, 1H), 7.62 (m, 1H), 7.40 (m, 1H), 7.29 (m, 1H), 7.26 (m, 1H), 7.13 (m, 1H), 7.08 (m, 1H), 6.93 (d, 1H), 6.47 (d, 1H), 5.20 (s, 2H), 3.97 (s, 2H), 3.08 (m, 2H), 2.85 (m, 1H), 1.57 (m, 6H). The reaction was quenched with 2N NaOH aqueous solution extracted with dichloromethane The combined organic layer and extracts were dried over anhydrous magnesium sulfate filtered concentrated The residue was purified by flash chromatography eluting with 20% methanol in dichloromethane

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

Procedure: 5-(4-(4-(3-fluorobenzyloxy)-3-chlorophenylamino)quinazolin-6-yl)furan-2-carbaldehyde (compound 1.7) and (dimethylphosphinoyl)methanamine (preparation: Maier, Ludwig Phosphorus, Sulfur and Silicon and the Related Elements, 53(1-4), 43-67; 1990) were suspended in dichloromethane (20 mL). Sequentially, acetic acid (3 drops) and sodium triacetoxyborohydride (2 equiv.) were added at room temperature. The mixture was stirred at room temperature until the starting material disappeared. The reaction was quenched with 2N NaOH aqueous solution and extracted with dichloromethane. The combined organic layer and extracts were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography, eluting with 20% methanol in dichloromethane to give the desired product as yellow crystalline solid. LCMS ESI(+) m/z: 566 (M+1). 1H NMR (300 MHz, CD3OD) δ 8.65 (s, 1H), 8.46 (s, 1H), 8.15 (m, 1H), 7.91 (d, 1H), 7.75 (m, 1H), 7.62 (m, 1H), 7.40 (m, 1H), 7.29 (m, 1H), 7.26 (m, 1H), 7.13 (m, 1H), 7.08 (m, 1H), 6.93 (d, 1H), 6.47 (d, 1H), 5.20 (s, 2H), 3.97 (s, 2H), 3.08 (m, 2H), 2.85 (m, 1H), 1.57 (m, 6H). The reaction was quenched with 2N NaOH aqueous solution extracted with dichloromethane The combined organic layer and extracts were dried over anhydrous magnesium sulfate filtered concentrated The residue was purified by flash chromatography eluting with 20% methanol in dichloromethane

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

Procedure: A solution of 4.95 g (3,5-Dichloro-2-pyridyloxy)-3,4-dinitrobenzene in 15 ml of toluene is refluxed, and 3.21 g of melted P,P-dimethyl-aminomethylphosphine oxide are added. After the initial evolution of nitrous gases has finished, the mixture is refluxed for a further 2 hours. The brown solution is subsequently concentrated by evaporation, and the residue is recrystallised from 20 ml of ethyl acetate and 100 ml of ether. There are obtained, in the form of yellow crystals, 4.9 g (84% of theory) of N-[2-nitro-5-(3,5-dichloro-2-pyridyloxy)-phenyl]-P,P-dimethyl-aminomethylphosphine oxide, m.p. 153°-155° C. the mixture is refluxed for a further 2 hours The brown solution is subsequently concentrated by evaporation the residue is recrystallised from 20 ml of ethyl acetate and 100 ml of ether

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

Procedure: A solution of 4.97 g of (5-trifluoromethyl-2-pyridyloxy)-3,4-dinitrobenzene in 15 ml of toluene is refluxed, and 3.21 g of melted P,P-dimethyl-aminomethylphosphine oxide are added dropwise. The mixture is refluxed for a further 2 hours, nitrous gases being evolved at the start. The brown solution is subsequently concentrated by evaporation, and the residue is recrystallised from 50 ml of ethyl acetate to thus obtain 4.10 g (70% of theory) of N-[2-nitro-5-(5-trifluoromethyl-2-pyridyloxy)-phenyl]-P,P-dimethyl-aminomethylphosphine oxide in the form of yellow crystals, m.p. 158°-160° C. The mixture is refluxed for a further 2 hours The brown solution is subsequently concentrated by evaporation the residue is recrystallised from 50 ml of ethyl acetate to thus obtain 4.10 g (70% of theory) of N-[2-nitro-5-(5-trifluoromethyl-2-pyridyloxy)-phenyl]-P,P-dimethyl-aminomethylphosphine oxide in the form of yellow crystals, m.p. 158°-160° C.

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

Procedure: A solution of 4.97 g of (5-trifluoromethyl-2-pyridyloxy)-3,4-dinitrobenzene in 15 ml of toluene is refluxed, and 3.21 g of melted P,P-dimethyl-aminomethylphosphine oxide are added dropwise. The mixture is refluxed for a further 2 hours, nitrous gases being evolved at the start. The brown solution is subsequently concentrated by evaporation, and the residue is recrystallised from 50 ml of ethyl acetate to thus obtain 4.10 g (70% of theory) of N-[2-nitro-5-(5-trifluoromethyl-2-pyridyloxy)-phenyl]-P,P-dimethyl-aminomethylphosphine oxide in the form of yellow crystals, m.p. 158°-160° C. The mixture is refluxed for a further 2 hours The brown solution is subsequently concentrated by evaporation the residue is recrystallised from 50 ml of ethyl acetate to thus obtain 4.10 g (70% of theory) of N-[2-nitro-5-(5-trifluoromethyl-2-pyridyloxy)-phenyl]-P,P-dimethyl-aminomethylphosphine oxide in the form of yellow crystals, m.p. 158°-160° C.

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

Procedure: 5-(4-(4-(3-fluorobenzyloxy)-3-chlorophenylamino)quinazolin-6-yl)furan-2-carbaldehyde (compound 1.7) and (dimethylphosphinoyl)methanamine (preparation: Maier, Ludwig Phosphorus, Sulfur and Silicon and the Related Elements, 53(1-4), 43-67; 1990) were suspended in dichloromethane (20 mL). Sequentially, acetic acid (3 drops) and sodium triacetoxyborohydride (2 equiv.) were added at room temperature. The mixture was stirred at room temperature until the starting material disappeared. The reaction was quenched with 2N NaOH aqueous solution and extracted with dichloromethane. The combined organic layer and extracts were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography, eluting with 20% methanol in dichloromethane to give the desired product as yellow crystalline solid. LCMS ESI(+) m/z: 566 (M+1). 1H NMR (300 MHz, CD3OD) δ 8.65 (s, 1H), 8.46 (s, 1H), 8.15 (m, 1H), 7.91 (d, 1H), 7.75 (m, 1H), 7.62 (m, 1H), 7.40 (m, 1H), 7.29 (m, 1H), 7.26 (m, 1H), 7.13 (m, 1H), 7.08 (m, 1H), 6.93 (d, 1H), 6.47 (d, 1H), 5.20 (s, 2H), 3.97 (s, 2H), 3.08 (m, 2H), 2.85 (m, 1H), 1.57 (m, 6H). The reaction was quenched with 2N NaOH aqueous solution extracted with dichloromethane The combined organic layer and extracts were dried over anhydrous magnesium sulfate filtered concentrated The residue was purified by flash chromatography eluting with 20% methanol in dichloromethane

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

Procedure: A solution of 4.95 g (3,5-Dichloro-2-pyridyloxy)-3,4-dinitrobenzene in 15 ml of toluene is refluxed, and 3.21 g of melted P,P-dimethyl-aminomethylphosphine oxide are added. After the initial evolution of nitrous gases has finished, the mixture is refluxed for a further 2 hours. The brown solution is subsequently concentrated by evaporation, and the residue is recrystallised from 20 ml of ethyl acetate and 100 ml of ether. There are obtained, in the form of yellow crystals, 4.9 g (84% of theory) of N-[2-nitro-5-(3,5-dichloro-2-pyridyloxy)-phenyl]-P,P-dimethyl-aminomethylphosphine oxide, m.p. 153°-155° C. the mixture is refluxed for a further 2 hours The brown solution is subsequently concentrated by evaporation the residue is recrystallised from 20 ml of ethyl acetate and 100 ml of ether

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

Procedure: A solution of 4.97 g of (5-trifluoromethyl-2-pyridyloxy)-3,4-dinitrobenzene in 15 ml of toluene is refluxed, and 3.21 g of melted P,P-dimethyl-aminomethylphosphine oxide are added dropwise. The mixture is refluxed for a further 2 hours, nitrous gases being evolved at the start. The brown solution is subsequently concentrated by evaporation, and the residue is recrystallised from 50 ml of ethyl acetate to thus obtain 4.10 g (70% of theory) of N-[2-nitro-5-(5-trifluoromethyl-2-pyridyloxy)-phenyl]-P,P-dimethyl-aminomethylphosphine oxide in the form of yellow crystals, m.p. 158°-160° C. The mixture is refluxed for a further 2 hours The brown solution is subsequently concentrated by evaporation the residue is recrystallised from 50 ml of ethyl acetate to thus obtain 4.10 g (70% of theory) of N-[2-nitro-5-(5-trifluoromethyl-2-pyridyloxy)-phenyl]-P,P-dimethyl-aminomethylphosphine oxide in the form of yellow crystals, m.p. 158°-160° C.