(2-propan-2-ylphenyl)hydrazine

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2-isopropyl-phenyl)-hydrazine 7.60 g, 0.0506 mol) (Asselin et al., J. Med. Chem. 1976, 19, 787-792) and acetone (100 mL) is added 1M HCl in EtOH (2 drops). The solution is heated at a reflux overnight. The solution is concentrated, dissolved in toluene (100 mL) and concentrated. The residue is dissolved in o-xylene (100 mL) and ZnCl2 (8.3 g) is added. The solution is heated at 140° C. for 2 hours, cooled to ambient temperature, diluted with EtOAc (200 mL), washed with sat. NH4Cl, dried over Na2SO4, filtered and concentrated. The residue is purified by ISCO (5%-15% EtOAc gradient to furnish the title compound (1.76 g, 10.16 mmol, 20%). 1H NMR (CDCl3), δ 1.43 (d, J=7.0 Hz, 6H), 2.50 (s, 3H), 3.17-3.29 (m, 1H), 6.24-6.27 (m, 1H), 7.02 (d, J=7.1 Hz, 1H), 7.07 (dd, J=7.5, 7.1 Hz, 1H), 7.39 (d, J=7.5 Hz, 1H), 7.85 (bs, 1H) ppm. LC/MS (m/z): calcd. for C12H15N (M+H)+: 174.1. found: 174.1. The solution is heated at a reflux overnight The solution is concentrated dissolved in toluene (100 mL) concentrated The residue is dissolved in o-xylene (100 mL) ZnCl2 (8.3 g) is added cooled to ambient temperature diluted with EtOAc (200 mL) washed with sat. NH4Cl dried over Na2SO4 filtered concentrated The residue is purified by ISCO (5%-15% EtOAc gradient

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

Procedure: A mixture of the substituted aniline, 2-isopropylaniline (27g, 0.2 mole), concentrated hydrochloric acid (150 ml) and water (160 ml) is stirred mechanically for 30 minutes at room temperature. After cooling to 0° C., the mixture is diazotized by adding dropwise a solution of sodium nitrite (14 g, 0.203 mole) in water (140 ml) over a period of 20 minutes. Stirring is continued for an additional one hour at 0° C. The diazo solution is reduced by adding dropwise a solution of stannous chloride dihydrate (112 g, 0.497 mole) in concentrated hydrochloric acid (90 ml) over a period of 30 minutes at -10° C. to -15° C. The reaction mixture is stirred for an additional 1.5 hour at -10° C. to -15° C. The precipitate is collected by filtration to give the hydrochloric acid addition salt of the title compound. The salt is purified further by dissolving it in ethanol, concentrating the solution and adding a saturated solution of hydrochloric acid in ether to give the hydrochloride salt with mp 206°-210° C. After cooling to 0° C. Stirring is continued for an additional one hour at 0° C The reaction mixture is stirred for an additional 1.5 hour at -10° C. to -15° C The precipitate is collected by filtration to give

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2-isopropyl-phenyl)-hydrazine 7.60 g, 0.0506 mol) (Asselin et al., J. Med. Chem. 1976, 19, 787-792) and acetone (100 mL) is added 1M HCl in EtOH (2 drops). The solution is heated at a reflux overnight. The solution is concentrated, dissolved in toluene (100 mL) and concentrated. The residue is dissolved in o-xylene (100 mL) and ZnCl2 (8.3 g) is added. The solution is heated at 140° C. for 2 hours, cooled to ambient temperature, diluted with EtOAc (200 mL), washed with sat. NH4Cl, dried over Na2SO4, filtered and concentrated. The residue is purified by ISCO (5%-15% EtOAc gradient to furnish the title compound (1.76 g, 10.16 mmol, 20%). 1H NMR (CDCl3), δ 1.43 (d, J=7.0 Hz, 6H), 2.50 (s, 3H), 3.17-3.29 (m, 1H), 6.24-6.27 (m, 1H), 7.02 (d, J=7.1 Hz, 1H), 7.07 (dd, J=7.5, 7.1 Hz, 1H), 7.39 (d, J=7.5 Hz, 1H), 7.85 (bs, 1H) ppm. LC/MS (m/z): calcd. for C12H15N (M+H)+: 174.1. found: 174.1. The solution is heated at a reflux overnight The solution is concentrated dissolved in toluene (100 mL) concentrated The residue is dissolved in o-xylene (100 mL) ZnCl2 (8.3 g) is added cooled to ambient temperature diluted with EtOAc (200 mL) washed with sat. NH4Cl dried over Na2SO4 filtered concentrated The residue is purified by ISCO (5%-15% EtOAc gradient

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

Procedure: A mixture of the substituted aniline, 2-isopropylaniline (27g, 0.2 mole), concentrated hydrochloric acid (150 ml) and water (160 ml) is stirred mechanically for 30 minutes at room temperature. After cooling to 0° C., the mixture is diazotized by adding dropwise a solution of sodium nitrite (14 g, 0.203 mole) in water (140 ml) over a period of 20 minutes. Stirring is continued for an additional one hour at 0° C. The diazo solution is reduced by adding dropwise a solution of stannous chloride dihydrate (112 g, 0.497 mole) in concentrated hydrochloric acid (90 ml) over a period of 30 minutes at -10° C. to -15° C. The reaction mixture is stirred for an additional 1.5 hour at -10° C. to -15° C. The precipitate is collected by filtration to give the hydrochloric acid addition salt of the title compound. The salt is purified further by dissolving it in ethanol, concentrating the solution and adding a saturated solution of hydrochloric acid in ether to give the hydrochloride salt with mp 206°-210° C. After cooling to 0° C. Stirring is continued for an additional one hour at 0° C The reaction mixture is stirred for an additional 1.5 hour at -10° C. to -15° C The precipitate is collected by filtration to give

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

Procedure: A mixture of the substituted aniline, 2-isopropylaniline (27g, 0.2 mole), concentrated hydrochloric acid (150 ml) and water (160 ml) is stirred mechanically for 30 minutes at room temperature. After cooling to 0° C, the mixture is diazotized by adding dropwise a solution of sodium nitrite (14 g, 0.203 mole) in water (140 ml) over a period of 20 minutes. Stirring is continued for an additional one hour at 0° C. The diazo solution is reduced by adding dropwise a solution of stannous chloride dihydrate (112 g, 0.497 mole) in concentrated hydrochloric acid (90 ml) over a period of 30 minutes at -10° C to -15° C. The reaction mixture is stirred for an additional 1.5 hour at -10° C to -15° C. The precipitate is collected by filtration to give the hydrochloric acid addition salt of the title compound. The salt is purified further by dissolving it in ethanol, concentrating the solution and adding a saturated solution of hydrochloric acid in either to give the hydrochloride salt with mp 206° - 210° C. After cooling to 0° C Stirring is continued for an additional one hour at 0° C The reaction mixture is stirred for an additional 1.5 hour at -10° C to -15° C The precipitate is collected by filtration to give

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2-isopropyl-phenyl)-hydrazine 7.60 g, 0.0506 mol) (Asselin et al., J. Med. Chem. 1976, 19, 787-792) and acetone (100 mL) is added 1M HCl in EtOH (2 drops). The solution is heated at a reflux overnight. The solution is concentrated, dissolved in toluene (100 mL) and concentrated. The residue is dissolved in o-xylene (100 mL) and ZnCl2 (8.3 g) is added. The solution is heated at 140° C. for 2 hours, cooled to ambient temperature, diluted with EtOAc (200 mL), washed with sat. NH4Cl, dried over Na2SO4, filtered and concentrated. The residue is purified by ISCO (5%-15% EtOAc gradient to furnish the title compound (1.76 g, 10.16 mmol, 20%). 1H NMR (CDCl3), δ 1.43 (d, J=7.0 Hz, 6H), 2.50 (s, 3H), 3.17-3.29 (m, 1H), 6.24-6.27 (m, 1H), 7.02 (d, J=7.1 Hz, 1H), 7.07 (dd, J=7.5, 7.1 Hz, 1H), 7.39 (d, J=7.5 Hz, 1H), 7.85 (bs, 1H) ppm. LC/MS (m/z): calcd. for C12H15N (M+H)+: 174.1. found: 174.1. The solution is heated at a reflux overnight The solution is concentrated dissolved in toluene (100 mL) concentrated The residue is dissolved in o-xylene (100 mL) ZnCl2 (8.3 g) is added cooled to ambient temperature diluted with EtOAc (200 mL) washed with sat. NH4Cl dried over Na2SO4 filtered concentrated The residue is purified by ISCO (5%-15% EtOAc gradient

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

Procedure: A mixture of the substituted aniline, 2-isopropylaniline (27g, 0.2 mole), concentrated hydrochloric acid (150 ml) and water (160 ml) is stirred mechanically for 30 minutes at room temperature. After cooling to 0° C., the mixture is diazotized by adding dropwise a solution of sodium nitrite (14 g, 0.203 mole) in water (140 ml) over a period of 20 minutes. Stirring is continued for an additional one hour at 0° C. The diazo solution is reduced by adding dropwise a solution of stannous chloride dihydrate (112 g, 0.497 mole) in concentrated hydrochloric acid (90 ml) over a period of 30 minutes at -10° C. to -15° C. The reaction mixture is stirred for an additional 1.5 hour at -10° C. to -15° C. The precipitate is collected by filtration to give the hydrochloric acid addition salt of the title compound. The salt is purified further by dissolving it in ethanol, concentrating the solution and adding a saturated solution of hydrochloric acid in ether to give the hydrochloride salt with mp 206°-210° C. After cooling to 0° C. Stirring is continued for an additional one hour at 0° C The reaction mixture is stirred for an additional 1.5 hour at -10° C. to -15° C The precipitate is collected by filtration to give