2-(2-methylphenyl)acetonitrile

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: To 50 ml of 6 N hydrochloric acid was added 11.8 g of 2-amino-4-chloro-5-sulfamylaniline and 10.4 g of 2-methylbenzyl cyanide. The reaction was refluxed for 22 hours and then concentrated in vacuo to a solid which was then added with stirring to 200 ml of 38% ammonium hydroxide. Filtration provided the free base as a semi-gum which was dissolved in 500 ml of methanol. The methanol solution was brought to a boil, charcoal added, and boiling continued for five minutes. Upon cooling, the suspension was filtered through Celite and the filtrate concentrated in vacuo to yield a solid, m.p. 226°-230°. The reaction was refluxed for 22 hours concentrated in vacuo to a solid which was then added Filtration provided the free base as a semi-gum which added Upon cooling the suspension was filtered through Celite the filtrate concentrated in vacuo to yield a solid, m.p. 226°-230°

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

Procedure: A solution of bis(2-chloroethyl)-N-(1,1-dimethylethoxy)carbonyl amine (1.438 g, 5.94 mmol) and 2-methylphenyl acetonitrile (600 mg, 3.96 mmol) in a 4:1 mixture of THF/DMF (15 mL) was treated with NaH (357.9 mg, 8.7 mmol) at 60° C. (3 d). The solvent was removed in vacuo, the residue dissolved in EtOAc (200 ml) and washed with saturated NaHCO3 (50 ml), H2O (2×50 ml), and saturated aqueous NaCl (50 ml), dried (Na2SO4) and concentrated in vacuo. PCTLC (SiO2, 6 mm, 100% hexane) afforded 4-cyano-N-(1,1-dimethylethoxy)carbonyl-4-(2-methylphenyl) piperidine as a yellow/orange oil. The solvent was removed in vacuo the residue dissolved in EtOAc (200 ml) washed with saturated NaHCO3 (50 ml), H2O (2×50 ml), and saturated aqueous NaCl (50 ml) dried (Na2SO4) concentrated in vacuo

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

Procedure: A thick walled tube was charged with 1H-pyrrole-2-carbaldehyde (2.0 g, 21.0 mmol), 2-methylphenylacetonitrile (2.5 g, 18.9 mmol, 0.9 equivalents), ethanol (75 ml), and 40% aqueous Triton B (4.0 ml, 3.3 mmol). The tube was sealed and heated to 90° C. for 4 days. Removal of the solvent, followed by chromatography on silica gel using dichloromethane/petroleum spirits (20:80) as eluant afforded a yellow solid (1.2 g). This is Compound 16 in Table 8. The tube was sealed Removal of the solvent

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

Procedure: A thick walled tube was charged with 1H-pyrrole-2-carbaldehyde (2.0 g, 21.0 mmol), 2-methylphenylacetonitrile (2.5 g, 18.9 mmol, 0.9 equivalents), ethanol (75 ml), and 40% aqueous Triton B (4.0 ml, 3.3 mmol). The tube was sealed and heated to 90° C. for 4 days. Removal of the solvent, followed by chromatography on silica gel using dichloromethane/petroleum spirits (20:80) as eluant afforded a yellow solid (1.2 g). This is Compound 16 in Table 8. The tube was sealed Removal of the solvent

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

Procedure: The title compound was prepared according to Example 1, starting from 2-methylbenzyl cyanide and 2,4-diamino-5-pyrimidine-carboxaldehyde; mp 300-302° C.

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

Procedure: A solution of bis(2-chloroethyl)-N-(1,1-dimethylethoxy)carbonyl amine (1.438 g, 5.94 mmol) and 2-methylphenyl acetonitrile (600 mg, 3.96 mmol) in a 4:1 mixture of THF/DMF (15 mL) was treated with NaH (357.9 mg, 8.7 mmol) at 60° C. (3 d). The solvent was removed in vacuo, the residue dissolved in EtOAc (200 ml) and washed with saturated NaHCO3 (50 ml), H20 (2×50 ml), and saturated aqueous NaCl (50 ml), dried (Na2SO4) and concentrated in vacuo. PCTLC (SiO2, 6mm, 100% hexane) afforded 4-cyano-N-(1,1-dimethylethoxy)carbonyl-4-(2-methylphenyl) piperidine as a yellow/orange oil. The solvent was removed in vacuo the residue dissolved in EtOAc (200 ml) washed with saturated NaHCO3 (50 ml), H20 (2×50 ml), and saturated aqueous NaCl (50 ml) dried (Na2SO4) concentrated in vacuo

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

Procedure: A solution of bis(2-chloroethyl)-N-(1,1-dimethylethoxy)carbonyl amine (1.438 g, 5.94 mmol) and 2-methylphenyl acetonitrile (600 mg, 3.96 mmol) in a 4:1 mixture of THF/DMF (15 mL) was treated with NaH (357.9 mg, 8.7 mmol) at 60° C. (3 d). The solvent was removed in vacuo, the residue dissolved in EtOAc (200 ml) and washed with saturated NaHCO3 (50 ml), H20 (2×50 ml), and saturated aqueous NaCl (50 ml), dried (Na2SO4) and concentrated in vacuo. PCTLC (SiO2, 6mm, 100% hexane) afforded 4-cyano-N-(1,1-dimethylethoxy)carbonyl-4-(2-methylphenyl) piperidine as a yellow/orange oil. The solvent was removed in vacuo the residue dissolved in EtOAc (200 ml) washed with saturated NaHCO3 (50 ml), H20 (2×50 ml), and saturated aqueous NaCl (50 ml) dried (Na2SO4) concentrated in vacuo

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

Procedure: The title compound was prepared according to Example 1, starting from 2-methylbenzyl cyanide and 2,4-diamino-5-pyrimidine-carboxaldehyde; mp 300°-302° C.

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

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

Procedure: The title compound was prepared according to Example 1, starting from 2-methylbenzyl cyanide and 2,4-diamino-5-pyrimidine-carboxaldehyde; mp 300°-302° C.