2-(2,6-dimethylpiperidin-1-yl)ethanamine

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: By the general method described in Example 1, 1-(2-aminoethyl)-2,6-dimethylpiperidine is reacted with propionyl isothiocyanate to give the title compound which may be hydrolysed with 10% sodium hydroxide to give N-2[(2,6-dimethylpiperidino)-ethyl]thiourea.

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

Procedure: By the general method described in Example 1, 1-(2-aminoethyl)-2,6-dimethylpiperidine is reacted with methyl isothiocyanate to give the title compound.

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

Procedure: By the general method described in Example 1, 1-(2-aminoethyl)-2,6-dimethylpiperidine is reacted with methyl isothiocyanate to give the title compound.

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: A mixture of nitrile 279 (3.13 g, 20.6 mmol) and Raney Nickel (50% w/w suspension in water, ca. 2 mL) in EtOH (30 mL) and cNH3 (2 mL) was stirred under H2 (60 psi) for 5 h. The suspension was filtered through Celite, washed with EtOH (3×10 mL) and the solvent evaporated to give diamine 280 (2.52 g, 78%) as a colourless oil which was used without further purification: 1H NMR δ 2.71-2.76 (m, 2H, CH2N), 2.63-2.68 (m, 2H, CH2N), 2.41-2.47 (m, 2H, 2×CH), 1.49-1.55 (m, 2H, CH2), 1.43 (br s, 2H, NH2), 1.25-1.42 (m, 4H, 2×CH2), 1.11 (d, J=6.3 Hz, 6H, 2×CH3); MS m/z 157 (MH+, 100%). The suspension was filtered through Celite washed with EtOH (3×10 mL) the solvent evaporated

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

Procedure: 2-(2,6-Dimethyl-1-piperidinyl)ethylamine (280) (0.66 g, 4.3 mmol) was added to a stirred solution of chloride 21 (314 mg, 1.4 mmol) in DME (50 mL) and the solution stirred at reflux temperature for 3 h. The solvent was evaporated and the residue partitioned between DCM (100 mL) and dilute aqueous NH3 solution (50 mL). The organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH/DCM, to give 1-oxide 38 (389 mg, 80%) as a yellow solid: mp (MeOH) 173-175° C.; 1H NMR δ 8.07 (s, 1H, H-9), 7.38 (s, 1H, H-5), 5.47 (br s, 1H, NH), 3.50-3.55 (m, 2H, CH2N), 2.96-3.03 (m, 4H, CH2N, CH2), 2.87-2.91 (m, 2H, CH2), 2.48-2.57 (m, 2H, CH2N), 2.10-2.18 (m, 2H, CH2), 1.64-1.69 (m, 1H, CH2), 1.53-1.58 (m, 2H, CH2), 1.33-1.38 (m, 1H, CH2), 1.24-1.31 (m, 2H, CH2), 1.20 (d, J=6.3 Hz, 6H, 2×CH3); 13C NMR δ 158.8, 154.5, 148.8, 143.2, 129.8, 120.6, 114.7, 57.2 (2), 47.5, 39.4, 34.3, 33.1 (2), 32.3, 25.8, 24.4, 21.7 (2). Anal. calcd for C19H27N5O: C, 66.8; H, 8.0; N, 20.5. Found: C, 66.8; H, 7.8; N, 20.6%. at reflux temperature for 3 h The solvent was evaporated the residue partitioned between DCM (100 mL) and dilute aqueous NH3 solution (50 mL) The organic fraction was dried the solvent evaporated The residue was purified by chromatography eluting with a gradient (0-10%) of MeOH/DCM

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

Procedure: 1.0 g of (R/S)-2-(3-acetoxy-2-oxo-1-pyrrolidinyl)acetic acid is placed in 15 ml of absolute tetrahydrofuran, whereupon 0.89 g of N,N'-carbonyldiimidazole is added in one portion. The mixture is stirred at room temperature until the gas evolution is complete. Thereafter, 0.86 g of 94.7% cis-(2-(2,6-dimethyl-1-piperidinyl)ethylamine is added and the mixture is left to stand overnight at room temperature and then evaporated. The residue is chromatographed on 60 g of aluminum oxide (activity grade III, neutral). The (R/S)-cis-N-[2-(2,6-dimethyl-1-piperidinyl)ethyl]-2-(3-acetoxy-2-oxo-1-pyrrolidinyl)acetamide which is eluted with methylene chloride has a melting point of 121°-122° after trituration with diethyl ether. is added in one portion the mixture is left evaporated The residue is chromatographed on 60 g of aluminum oxide (activity grade III, neutral) The (R/S)-cis-N-[2-(2,6-dimethyl-1-piperidinyl)ethyl]-2-(3-acetoxy-2-oxo-1-pyrrolidinyl)acetamide which is eluted with methylene chloride

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

Procedure: By the general method described in Example 1, 1-(2-aminoethyl)-2,6-dimethylpiperidine is reacted with propionyl isothiocyanate to give the title compound which may be hydrolysed with 10% sodium hydroxide to give N-2[(2,6-dimethylpiperidino)-ethyl]thiourea.

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

Procedure: By the general method described in Example 1, 1-(2-aminoethyl)-2,6-dimethylpiperidine is reacted with methyl isothiocyanate to give the title compound.