1-amino-2-cyclopropylpropan-2-ol

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

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

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: 5-Bromo-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinic acid (1.1 g, 3.0 mmol) was dissolved in DMF (25 mL). To the solution was added TBTU (1.06 g, 3.3 mmol), N,N-diisopropylethyl amine (2.54 mL, 15 mmol) and α-(aminomethyl)-α-methyl-cyclopropanemethanol (0.38 g, 3.3 mmol). The reaction mixture was stirred for 16 h at room temperature. The solvent was evaporated in vacuo and the residue dissolved in ethyl acetate (20 mL), washed with sodium hydroxide solution (0.5 N) and brine. Organic phases were pooled, dried with MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (SiO2, heptane/ethyl acetate) to give the title compound (0.38 g) as a light yellow solid, MS (ISP) 462.9, 464.9 (M−H)+. The solvent was evaporated in vacuo the residue dissolved in ethyl acetate (20 mL) washed with sodium hydroxide solution (0.5 N) and brine dried with MgSO4 concentrated in vacuo The residue was purified by flash chromatography (SiO2, heptane/ethyl acetate)

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

Procedure: 5-Bromo-6-(2,2,2-trifluoro-ethoxy)-2-trifluoromethyl-nicotinic acid (1.1 g, 3.0 mmol) was dissolved in DMF (25 mL). To the solution was added TBTU (1.06 g, 3.3 mmol), N,N-diisopropylethyl amine (2.54 mL, 15 mmol) and α-(aminomethyl)-α-methyl-cyclopropanemethanol (0.38 g, 3.3 mmol). The reaction mixture was stirred for 16 h at room temperature. The solvent was evaporated in vacuo and the residue dissolved in ethyl acetate (20 mL), washed with sodium hydroxide solution (0.5 N) and brine. Organic phases were pooled, dried with MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (SiO2, heptane/ethyl acetate) to give the title compound (0.38 g) as a light yellow solid, MS (ISP) 462.9, 464.9 (M−H)+. The solvent was evaporated in vacuo the residue dissolved in ethyl acetate (20 mL) washed with sodium hydroxide solution (0.5 N) and brine dried with MgSO4 concentrated in vacuo The residue was purified by flash chromatography (SiO2, heptane/ethyl acetate)

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: The title compound was synthesized in analogy to the procedure described for the preparation of Example 43, using 5-bromo-6-chloro-nicotinic acid methyl ester, cyclopropylmethanol (commercially available), 4-trifluoromethoxyphenylboronic acid (commercially available) and rac-1-amino-2-cyclopropyl-propan-2-ol (commercially available) as starting materials. The two enantiomers were separated by column chromatography on chiral phase. MS (ISP): 451.1 (M+H+). described for the preparation of Example 43 The two enantiomers were separated by column chromatography on chiral phase

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

Procedure: The title compound was synthesized in analogy to the procedure described for the preparation of Example 43, using 5-bromo-6-chloro-nicotinic acid methyl ester, cyclopropylmethyl methylamine hydrochloride, (commercially available), 4-fluorophenyl-boronic acid (commercially available) and rac-1-amino-2-cyclopropyl-propan-2-ol (commercially available) as starting materials. MS (ISP): 398.0 (M+H+). described for the preparation of Example 43

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

Procedure: The title compound was synthesized in analogy to the procedure described for the preparation of Example 43, using 5-bromo-6-chloro-nicotinic acid methyl ester, piperidine (commercially available), 4-chlorophenyl-boronic acid (commercially available) and rac-1-amino-2-cyclopropyl-propan-2-ol (commercially available) as starting materials. MS (ISP): 414.4 (M+H+). described for the preparation of Example 43

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

Procedure: The title compound was synthesized in analogy to the procedure described for the preparation of Example 43, using 5-bromo-6-chloro-nicotinic acid methyl ester, cyclopropylmethanol (commercially available), 4-fluorophenylboronic acid (commercially available) and rac-1-amino-2-cyclopropyl-propan-2-ol (commercially available) as starting materials. The two enantiomers were separated by column chromatography on chiral phase. MS (ISP): 385.3 (M+H+). described for the preparation of Example 43 The two enantiomers were separated by column chromatography on chiral phase