sodium;propan-1-olate

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

Procedure: In a similar manner to Example 63 reaction of 7-methylsulphonyl-4-oxo-2-(2-propoxyphenyl)-3,4-dihydropyrimido[4,5-d]pyrimidine (0.54 g) and sodium propoxide solution (from sodium, 0.17 g, and n-propanol, 25 ml) yielded the title compound, 0.19 g, m.p. 157-8° C. (recrystallized from n-propanol). yielded the title compound, 0.19 g, m.p. 157-8° C. (recrystallized from n-propanol)

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

Procedure: To 30 g (167 mmole) of O-ethyl dichlorothiophosphate in 100 ml of tetrahydrofuran (THF) and cooled to -70° C. was added a solution of sodium propoxide (from 7.4 g of 60% NaH (184 mmole) and 11 g (176 mmole) of 1-propanol) in 50 ml of THF. After warming to room temperature over 2 hours, the THF was removed in vacuo and the residue was partitioned between 50 ml diethyl ether, 50 ml hexanes, and 25 ml cold water. The organic layer was dried over magnesium sulfate, concentrated in vacuo, and distilled (bp 45°-50° C. 1 torr) yielding 20 g of the title compound, an oil. nmr 1.0 t 3H, 1.4 t 3H, 1.8 sextet 2H, 4.4M 4H. the THF was removed in vacuo the residue was partitioned between 50 ml diethyl ether, 50 ml hexanes, and 25 ml cold water The organic layer was dried over magnesium sulfate concentrated in vacuo distilled (bp 45°-50° C. 1 torr)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 20.0 g (71 mmol) of 2-amino-4-trichloromethyl-6-trifluoromethyl-1,3,5-triazine were added at 22° C. to a solution of 0.58 g (7.1 mmol) of sodium propanolate in 40 ml of propanol. The resulting yellow mixture was then heated at 75° C. for 30 minutes, after which a further 0.58 g (7.1 mmol) of sodium propanolate in 10 ml of propanol was added and the mixture was heated at 75° C. for 10 minutes. The reaction mixture was cooled to 20° C. and then neutralized with 2 normal aqueous hydrochloric acid. After this, most of the solvent was removed under reduced pressure, and the residue was slowly diluted with 40 ml of water. The solid which formed was separated off, washed with 5 ml of water and dried at 40° C. under reduced pressure. the mixture was heated at 75° C. for 10 minutes The reaction mixture was cooled to 20° C. After this, most of the solvent was removed under reduced pressure the residue was slowly diluted with 40 ml of water The solid which formed was separated off washed with 5 ml of water dried at 40° C. under reduced pressure

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 20.0 g (71 mmol) of 2-amino-4-trichloromethyl-6-trifluoromethyl-1,3,5-triazine were added at 22° C. to a solution of 0.58 g (7.1 mmol) of sodium propanolate in 40 ml of propanol. The resulting yellow mixture was then heated at 75° C. for 30 minutes, after which a further 0.58 g (7.1 mmol) of sodium propanolate in 10 ml of propanol was added and the mixture was heated at 75° C. for 10 minutes. The reaction mixture was cooled to 20° C. and then neutralized with 2 normal aqueous hydrochloric acid. After this, most of the solvent was removed under reduced pressure, and the residue was slowly diluted with 40 ml of water. The solid which formed was separated off, washed with 5 ml of water and dried at 40° C. under reduced pressure. the mixture was heated at 75° C. for 10 minutes The reaction mixture was cooled to 20° C. After this, most of the solvent was removed under reduced pressure the residue was slowly diluted with 40 ml of water The solid which formed was separated off washed with 5 ml of water dried at 40° C. under reduced pressure

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

Procedure: By treating the product of Example 11 according to the procedure of Example 3, replacing the sodium ethoxide with sodium propoxide, 1-benzyl-4-propoxy-5,6-dihydrobenzo[5,6]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridin-11(1H)one is obtained.

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

Procedure: By treating the product of Example 11 according to the procedure of Example 3, replacing the sodium ethoxide with sodium propoxide, 1-benzyl-4-propoxy-5,6-dihydrobenzo[5,6]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridin-11(1H)one is obtained.

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

Procedure: By treating the product of Example 11 according to the procedure of Example 3, replacing the sodium ethoxide with sodium propoxide, 1-benzyl-4-propoxy-5,6-dihydrobenzo[5,6]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridin-11(1H)one is obtained.

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

Procedure: By treating the product of Example 11 according to the procedure of Example 3, replacing the sodium ethoxide with sodium propoxide, 1-benzyl-4-propoxy-5,6-dihydrobenzo[5,6]cyclohepta[1,2-b]pyrazolo[4,3-e]pyridin-11(1H)one is obtained.

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

Procedure: To 30 g (167 mmole) of O-ethyl dichlorothiophosphate in 100 ml of tetrahydrofuran (THF) and cooled to -70° C. was added a solution of sodium propoxide (from 7.4 g of 60% Nail (184 mmole) and 11 g (176 mmole) of 1-propanol) in 50 ml of THF. After warming to room temperature over 2 hours, the THF was removed in vacuo and the residue was partitioned between 50 ml diethyl ether, 50 ml hexanes, and 25 ml cold water. The organic layer was dried over magnesium sulfate, concentrated in vacuo, and distilled (bp 45°-50° C. 1 torr) yielding 20 g of the title compound, an oil. nmr 1.0 t 3H, 1.4 t 3H, 1.8 sextet 2H, 4.4 M 4H. the THF was removed in vacuo the residue was partitioned between 50 ml diethyl ether, 50 ml hexanes, and 25 ml cold water The organic layer was dried over magnesium sulfate concentrated in vacuo distilled (bp 45°-50° C. 1 torr)

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

Procedure: To 30 g (167 mmole) of O-ethyl dichlorothiophosphate in 100 ml of tetrahydrofuran (THF) and cooled to -70° C. was added a solution of sodium propoxide (from 7.4 g of 60% Nail (184 mmole) and 11 g (176 mmole) of 1-propanol) in 50 ml of THF. After warming to room temperature over 2 hours, the THF was removed in vacuo and the residue was partitioned between 50 ml diethyl ether, 50 ml hexanes, and 25 ml cold water. The organic layer was dried over magnesium sulfate, concentrated in vacuo, and distilled (bp 45°-50° C. 1 torr) yielding 20 g of the title compound, an oil. nmr 1.0 t 3H, 1.4 t 3H, 1.8 sextet 2H, 4.4 M 4H. the THF was removed in vacuo the residue was partitioned between 50 ml diethyl ether, 50 ml hexanes, and 25 ml cold water The organic layer was dried over magnesium sulfate concentrated in vacuo distilled (bp 45°-50° C. 1 torr)

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

Procedure: To 30 g (167 mmole) of O-ethyl dichlorothiophosphate in 100 ml of tetrahydrofuran (THF) and cooled to -70° C. was added a solution of sodium propoxide (from 7.4 g of 60% Nail (184 mmole) and 11 g (176 mmole) of 1-propanol) in 50 ml of THF. After warming to room temperature over 2 hours, the THF was removed in vacuo and the residue was partitioned between 50 ml diethyl ether, 50 ml hexanes, and 25 ml cold water. The organic layer was dried over magnesium sulfate, concentrated in vacuo, and distilled (bp 45°-50° C. 1 torr) yielding 20 g of the title compound, an oil. nmr 1.0 t 3H, 1.4 t 3H, 1.8 sextet 2H, 4.4 M 4H. the THF was removed in vacuo the residue was partitioned between 50 ml diethyl ether, 50 ml hexanes, and 25 ml cold water The organic layer was dried over magnesium sulfate concentrated in vacuo distilled (bp 45°-50° C. 1 torr)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a sodium propan-1-olate solution, prepared by addition of sodium (36 mg, 1.58 mmol) to propanol (1 mL), was added 2,6-dibromopyridine (250 mg, 1.06 mmol). The mixture was stirred at 90° C. for 2 h, then was diluted with EtOAc. The organic phase was washed with water (2×) and brine, dried (Na2SO4) and concentrated. The crude material was purified by flash chromatography (0 to 10% EtOAc/hexanes gradient) to afford 189 mg of Intermediate 161.1 as a colorless oil. LCMS (2 min gradient) RT=1.82 min, 216.1 (M+H)+. The organic phase was washed with water (2×) and brine dried (Na2SO4) concentrated The crude material was purified by flash chromatography (0 to 10% EtOAc/hexanes gradient)