Benzyldiisopropylamine

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

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

Procedure: 2-methoxyacetyl chloride (0.033 ml) was added in one portion to a stirred ice-cooled suspension of 3-(1,3-benzoxazol-2-yl)-5-[1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine (100 mg) and N-benzyl-N-isopropyl-propan-2-amine on polystyrene (185 mg, 3 mmol/g) in dichloromethane (5 ml) and THF (5 ml). The resulting suspension was stirred at room temperature for 2 hours. The resin was filtered, rinsed with dichloromethane/methanol. The filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 4% methanol in dichloromethane. After evaporation of the solvants, the resulting solid was triturated in acetonitrile to give the title compound (79 mg). NMR Spectrum: (CDCl3): 1.97-2.11 (m, 2H), 2.22-2.35 (m, 2H), 2.80-2.91 (m, 1H), 3.17-3.29 (m, 1H), 3.46 (s, 3H), 4.06-4.23 (m, 3H), 4.38-4.47 (m, 1H), 4.69-4.80 (m, 1H), 7.08 (bs, 2H), 7.35-7.42 (m, 2H), 7.58-7.63 (m, 1H), 7.69 (s, 1H), 7.73-7.78 (m, 1H), 7.80 (s, 1H), 8.35 (d, 1H), 8.41 (d, 1H); Mass spectrum: M+H+ 433. cooled The resin was filtered rinsed with dichloromethane/methanol The filtrate was concentrated to dryness The crude product was purified by flash chromatography on silica gel eluting with 0 to 4% methanol in dichloromethane After evaporation of the solvants the resulting solid was triturated in acetonitrile

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

Procedure: 2-methoxyacetyl chloride (0.033 ml) was added in one portion to a stirred ice-cooled suspension of 3-(1,3-benzoxazol-2-yl)-5-[1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine (100 mg) and N-benzyl-N-isopropyl-propan-2-amine on polystyrene (185 mg, 3 mmol/g) in dichloromethane (5 ml) and THF (5 ml). The resulting suspension was stirred at room temperature for 2 hours. The resin was filtered, rinsed with dichloromethane/methanol. The filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 4% methanol in dichloromethane. After evaporation of the solvants, the resulting solid was triturated in acetonitrile to give the title compound (79 mg). NMR Spectrum: (CDCl3): 1.97-2.11 (m, 2H), 2.22-2.35 (m, 2H), 2.80-2.91 (m, 1H), 3.17-3.29 (m, 1H), 3.46 (s, 3H), 4.06-4.23 (m, 3H), 4.38-4.47 (m, 1H), 4.69-4.80 (m, 1H), 7.08 (bs, 2H), 7.35-7.42 (m, 2H), 7.58-7.63 (m, 1H), 7.69 (s, 1H), 7.73-7.78 (m, 1H), 7.80 (s, 1H), 8.35 (d, 1H), 8.41 (d, 1H); Mass spectrum: M+H+ 433. cooled The resin was filtered rinsed with dichloromethane/methanol The filtrate was concentrated to dryness The crude product was purified by flash chromatography on silica gel eluting with 0 to 4% methanol in dichloromethane After evaporation of the solvants the resulting solid was triturated in acetonitrile

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

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

Procedure: Heptan-1-amine (1 g, 8.679 mmol) was dissolved in dry THF under N2 and polymer supported N-benzyl-N,N-diisopropylamine (4.955 g, 26.038 mmol) was added. The mixture was stirred for 30 min and cooled to 0° C. and (4-chlorophenyl)acetyl chloride (1.969 g, 10.415 mmol) was added. The solution was stirred overnight at room temperature. The excess of (4-chlorophenyl)acetyl chloride was removed by filtering the mixture through an NH2 cartridge. The solvent was removed by evaporation. The crude was purified by preparative HPLC (started with isocratic acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product containing fractions were pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4) and the solvent was removed by evaporation to give 1.045 g of 2-(4-chlorophenyl)-N-heptylacetamide (yield 45.0%). was added The solution was stirred overnight at room temperature The excess of (4-chlorophenyl)acetyl chloride was removed by filtering the mixture through an NH2 cartridge The solvent was removed by evaporation The crude was purified by preparative HPLC ( the acetonitrile concentration was increased to 100% a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min) The product containing fractions the acetonitrile was removed by evaporation EtOAc (10 ml) was added the organic phase was washed with two portions of brine dried (MgSO4) the solvent was removed by evaporation

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

Procedure: Heptan-1-amine (1 g, 8.679 mmol) was dissolved in dry THF under N2 and polymer supported N-benzyl-N,N-diisopropylamine (4.955 g, 26.038 mmol) was added. The mixture was stirred for 30 min and cooled to 0° C. and phenylacetyl chloride (1.610 g, 10.415 mmol) was added. The solution was stirred overnight at room temperature. The excess of phenylacetyl chloride was removed by filtering the mixture through an NH2 cartridge. The solvent was removed by evaporation. The crude was purified by preparative HPLC (started with isocratic acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product containing fractions were pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4) and the solvent was removed by evaporation to give 0.886 g of N-heptyl-2-phenylacetamide (yield 43.7%). was added The solution was stirred overnight at room temperature The excess of phenylacetyl chloride was removed by filtering the mixture through an NH2 cartridge The solvent was removed by evaporation The crude was purified by preparative HPLC ( the acetonitrile concentration was increased to 100% a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min) The product containing fractions the acetonitrile was removed by evaporation EtOAc (10 ml) was added the organic phase was washed with two portions of brine dried (MgSO4) the solvent was removed by evaporation

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

Procedure: Heptan-1-amine (1 g, 8.679 mmol) was dissolved in dry THF under N2 and polymer supported N-benzyl-N,N-diisopropylamine (4.955 g, 26.038 mmol) was added. The mixture was stirred for 30 min and cooled to 0 degrees and phenylacetyl chloride (1.610 g, 10.415 mmol) was added. The solution was stirred overnight at room temperature. The excess of phenylacetyl chloride was removed by filtering the mixture through an NH2 cartridge. The solvent was removed by evaporation. The crude was purified by preparative HPLC (started with isocratic acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product containing fractions were pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4) and the solvent was removed by evaporation to give 0.886 g of N-heptyl-2-phenylacetamide (yield 43.7%). was added cooled to 0 degrees The solution was stirred overnight at room temperature The excess of phenylacetyl chloride was removed by filtering the mixture through an NH2 cartridge The solvent was removed by evaporation The crude was purified by preparative HPLC ( the acetonitrile concentration was increased to 100% a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min) The product containing fractions the acetonitrile was removed by evaporation EtOAc (10 ml) was added the organic phase was washed with two portions of brine dried (MgSO4) the solvent was removed by evaporation

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

Procedure: Heptan-1-amine (1 g, 8.679 mmol) was dissolved in dry THF under N2 and polymer supported N-benzyl-N,N-diisopropylamine (4.955 g, 26.038 mmol) was added. The mixture was stirred for 30 min and cooled to 0 degrees and (4-chlorophenyl)acetyl chloride (1.969 g, 10.415 mmol) was added. The solution was stirred overnight at room temperature. The excess of (4-chlorophenyl)acetyl chloride was removed by filtering the mixture through an NH2 cartridge. The solvent was removed by evaporation. The crude was purified by preparative HPLC (started with isocratic acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product containing fractions were pooled and the acetonitrile was removed by evaporation EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4) and the solvent was removed by evaporation to give 1.045 g of 2-(4-chlorophenyl)-N-heptylacetamide (yield 45.0%). was added cooled to 0 degrees The solution was stirred overnight at room temperature The excess of (4-chlorophenyl)acetyl chloride was removed by filtering the mixture through an NH2 cartridge The solvent was removed by evaporation The crude was purified by preparative HPLC ( the acetonitrile concentration was increased to 100% a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min) The product containing fractions the acetonitrile was removed by evaporation EtOAc (10 ml) was added the organic phase was washed with two portions of brine dried (MgSO4) the solvent was removed by evaporation

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

Procedure: 2-methoxyacetyl chloride (0.033 ml) was added in one portion to a stirred ice-cooled suspension of 3-(1,3-benzoxazol-2-yl)-5-[1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine (100 mg) and N-benzyl-N-isopropyl-propan-2-amine on polystyrene (185 mg, 3 mmol/g) in dichloromethane (5 ml) and THF (5 ml). The resulting suspension was stirred at room temperature for 2 hours. The resin was filtered, rinsed with dichloromethane/methanol. The filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 4% methanol in dichloromethane. After evaporation of the solvants, the resulting solid was triturated in acetonitrile to give the title compound (79 mg). NMR Spectrum: (CDCl3): 1.97-2.11 (m, 2H), 2.22-2.35 (m, 2H), 2.80-2.91 (m, 1H), 3.17-3.29 (m, 1H), 3.46 (s, 3H), 4.06-4.23 (m, 3H), 4.38-4.47 (m, 1H), 4.69-4.80 (m, 1H), 7.08 (bs, 2H), 7.35-7.42 (m, 2H), 7.58-7.63 (m, 1H), 7.69 (s, 1H), 7.73-7.78 (m, 1H), 7.80 (s, 1H), 8.35 (d, 1H), 8.41 (d, 1H); Mass spectrum: M+H+ 433. cooled The resin was filtered rinsed with dichloromethane/methanol The filtrate was concentrated to dryness The crude product was purified by flash chromatography on silica gel eluting with 0 to 4% methanol in dichloromethane After evaporation of the solvants the resulting solid was triturated in acetonitrile