2-tert-butylbenzoyl chloride

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 5-nitroanthranilic acid (24.6 g, 135 mmol) and pyridine (14.2 mL, 175 mmol) in N,N-dimethylformamide (140 mL) cooled to 0° C. was added tert-butylbenzoyl chloride (31.6 mL, 162 mmol). After stirring for 1 h, the reaction mixture was heated at 75° C. for 4 h, cooled, and poured into an ice/water mixture. The resulting solid was filtered, washed with water and a 1:2 mixture of diethyl ether/hexanes, and dried in vacuo at 150° C. for 2 h to give 37.1 g (80%) of the title compound as a light brown solid; mp 245-9° C. MS-FD m/e 342 (p) Analysis for C18H18N2O5: Calc: C, 63.15; H, 5.30; N, 8.18; Found: C, 62.85; H, 5.05; N, 8.48. the reaction mixture was heated at 75° C. for 4 h cooled The resulting solid was filtered washed with water a 1:2 mixture of diethyl ether/hexanes dried in vacuo at 150° C. for 2 h

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

Procedure: 2-tert-butyl-N-ethylbenzamide was prepared from 2-tert-butylbenzoyl chloride, prepared in Example 186, and 70% ethylamine in water according to the method of step b of Example 248.

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

Procedure: A mixture of 2-tert-butylbenzoic acid (15.7 g, 88.2 mmol) and thionyl chloride (19.3 mL, 265 mmol) was stirred at RT for 1 day, then was concentrated and stripped from toluene (2×) under vacuum. The compound from example k (19.94 g, 176.5 mmol) was added to a solution of this crude 2-tert-butylbenzoyl chloride in toluene (90 mL), and the mixture was heated at 100° C. for 3 h, then was stirred at room temperature overnight. The resulting mixture was cooled with an ice-water bath, and Et3N (13.4 g, 132.4 mmol) was added, followed by the dropwise addition of methanol (5.65 g, 176.6 mmol). The resulting reaction mixture was stirred at RT and monitored to completion by GLC, then was partitioned between ether and sat aq NaHCO3. The ether extract was dried (MgSO4), concentrated, and purified by flash chromatography with 1:9 EtOAc/hexanes to afford 20.8 g of the title compound as a pale yellow oil, a 77% yield. was concentrated the mixture was heated at 100° C. for 3 h was stirred at room temperature overnight The resulting mixture was cooled with an ice-water bath The resulting reaction mixture was stirred at RT was partitioned between ether The ether extract was dried (MgSO4) concentrated purified by flash chromatography with 1:9 EtOAc/hexanes

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

Procedure: 2-tert-butyl-N-ethylbenzamide was prepared from 2-tert-butylbenzoyl chloride, prepared in Example 186, and 70% ethylamine in water according to the method of step b of Example 248.

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

Procedure: A mixture of 2-tert-butylbenzoic acid (15.7 g, 88.2 mmol) and thionyl chloride (19.3 mL, 265 mmol) was stirred at RT for 1 day, then was concentrated and stripped from toluene (2×) under vacuum. The compound from example k (19.94 g, 176.5 mmol) was added to a solution of this crude 2-tert-butylbenzoyl chloride in toluene (90 mL), and the mixture was heated at 100° C. for 3 h, then was stirred at room temperature overnight. The resulting mixture was cooled with an ice-water bath, and Et3N (13.4 g. 132.4 mmol) was added, followed by the dropwise addition of methanol (5.65 g, 176.6 mmol). The resulting reaction mixture was stirred at RT and monitored to completion by GLC, then was partitioned between ether and sat aq NaHCO3. The ether extract was dried (MgSO4), concentrated, and purified by flash chromatography with 1:9 EtOAc/hexanes to afford 20.8 g of the title compound as a pale yellow oil, a 77% yield. was concentrated the mixture was heated at 100° C. for 3 h was stirred at room temperature overnight The resulting mixture was cooled with an ice-water bath The resulting reaction mixture was stirred at RT was partitioned between ether The ether extract was dried (MgSO4) concentrated purified by flash chromatography with 1:9 EtOAc/hexanes

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

Procedure: 2-tert-butyl-N-ethylbenzamide was prepared from 2-tert-butylbenzoyl chloride, prepared in Example 186, and 70% ethylamine in water according to the method of step b of Example 248.

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

Procedure: A mixture of 2-tert-butylbenzoic acid (15.7 g, 88.2 mmol) and thionyl chloride (19.3 mL, 265 mmol) was stirred at RT for 1 day, then was concentrated and stripped from toluene (2×) under vacuum. The compound from example k (19.94 g, 176.5 mmol) was added to a solution of this crude 2-tert-butylbenzoyl chloride in toluene (90 mL), and the mixture was heated at 100° C. for 3 h, then was stirred at room temperature overnight. The resulting mixture was cooled with an ice-water bath, and Et3N (13.4 g, 132.4 mmol) was added, followed by the dropwise addition of methanol (5.65 g, 176.6 mmol). The resulting reaction mixture was stirred at RT and monitored to completion by GLC, then was partitioned between ether and sat aq NaHCO3. The ether extract was dried (MgSO4), concentrated, and purified by flash chromatography with 1:9 EtOAc/hexanes to afford 20.8 g of the title compound as a pale yellow oil, a 77% yield. was concentrated the mixture was heated at 100° C. for 3 h was stirred at room temperature overnight The resulting mixture was cooled with an ice-water bath The resulting reaction mixture was stirred at RT was partitioned between ether The ether extract was dried (MgSO4) concentrated purified by flash chromatography with 1:9 EtOAc/hexanes

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

Procedure: 2-tert-butyl-N-ethylbenzamide was prepared from 2-tert-butylbenzoyl chloride, prepared in Example 186, and 70% ethylamine in water according to the method of step b of Example 248.

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

Procedure: A mixture of 2-tert-butylbenzoic acid (15.7 g, 88.2 mmol) and thionyl chloride (19.3 mL, 265 mmol) was stirred at RT for 1 day, then was concentrated and stripped from toluene (2X) under vacuum. The compound from example k (19.94 g, 176.5 mmol) was added to a solution of this crude 2-tert-butylbenzoyl chloride in toluene (90 mL), and the mixture was heated at 100° C. for 3 h, then was stirred at room temperature overnight. The resulting mixture was cooled with an ice-water bath, and Et3N (13.4 g, 132.4 mmol) was added, followed by the dropwise addition of methanol (5.65 g, 176.6 mmol). The resulting reaction mixture was stirred at RT and monitored to completion by GLC, then was partitioned between ether and sat aq NaHCO3. The ether extract was dried (MgSO4), concentrated, and purified by flash chromatography with 1:9 EtOAc/hexanes to afford 20.8 g of the title compound as a pale yellow oil, a 77% yield. was concentrated the mixture was heated at 100° C. for 3 h was stirred at room temperature overnight The resulting mixture was cooled with an ice-water bath The resulting reaction mixture was stirred at RT was partitioned between ether The ether extract was dried (MgSO4) concentrated purified by flash chromatography with 1:9 EtOAc/hexanes

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

Procedure: The 6-(p-tert.butylbenzoyl)-3-chloro-5,6,7,8-tetrahydropyrido[4,3-c]pyridazine, required as starting material, may be obtained in a manner analogous to that described in Example 8 (g), from 34.2 g of 3-chloro-5,6,7,8-tetrahydropyrido[4,3-c]pyridazine maleate and 25 g of tert.butylbenzoyl chloride. M.P. 157°-160° (decomp., from 95% ethanol). may be obtained in a manner analogous to

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

Procedure: The 6-(p-tert.butylbenzoyl)-3-chloro-5,6,7,8-tetrahydropyrido[4,3-c]pyridazine, required as starting material, may be obtained in a manner analogous to that described in Example 8 (g), from 34.2 g of 3-chloro-5,6,7,8-tetrahydropyrido[4,3-c]pyridazine maleate and 25 g of tert.butylbenzoyl chloride. M.P. 157°-160° (decomp., from 95% ethanol). may be obtained in a manner analogous to

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

Procedure: 2-tert-butyl-N-ethylbenzamide was prepared from 2-tert-butylbenzoyl chloride, prepared in Example 186, and 70% ethylamine in water according to the method of step b of Example 248.