tert-butyl (2S)-2-amino-4-methylsulfanylbutanoate

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

Procedure: A solution of pentafluorophenyl 5-[(E)-3-(imidazol-1-yl)prop-1-en-1-yl]-2-(4-fluorophenethyl)benzoate (0.36 g, 0.7 mmol), L-methionine-tert-butyl ester(0.173 g, 0.84 mmol) and 1-hydroxy-7-azabenzotriazole (0.1 g, 0.73 mmol) in DMF (2 ml) was stirred at ambient temperature overnight. After evaporation of the solvent, the residue was taken up in ethyl acetate, washed with 5% sodium hydrogen carbonate solution and saturated brine and evaporated to dryness. The residue was then purified by flash chromatography eluting with dichloromethane/ethanol (97/3) to give the title compound. Yield: 50% After evaporation of the solvent washed with 5% sodium hydrogen carbonate solution and saturated brine evaporated to dryness The residue was then purified by flash chromatography eluting with dichloromethane/ethanol (97/3)

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

Procedure: When in the procedure of Example 1, Step (b), thianthrene-2-sulfonyl chloride is replaced by phenoxathiine-2-sulfonyl chloride and (L)-valine-t-butyl ester is replaced with (L)-methionine-t-butyl ester, (S)-4-methanesulfinyl-2-(phenoxathiine-2-sulfonylamino)-butyric acid is obtained as a white solid;

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

Procedure: The title compound was prepared from 3-(4-fluorophenethyl)-6-[1-(4-fluorophenyl)-2-(1-methylimidazol-5-yl)ethoxy]pyridin-2-carboxylic acid by a similar route to that described for the preparation of tert-butyl (2S)-2-{3-(4-fluorophenethyl)-6-[1-(4-fluorophenyl)-2-(1-methylimidazol-5-yl)ethoxy]pyrid-2-oylamino}-4-methylsulfanylbutyrate but using L-methionine cyclopentyl ester rather than L-methionine-tert-butyl ester.

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

Procedure: The title compound was prepared in 80% yield from 5-(1-(4-fluorophenyl)-2-(imidazol-1-yl)ethoxy)-2-(4-fluorophenethyl)benzoic acid and L-methionine tert-butyl ester by a similar method to that used for Example 34. 1H NMR (DMSO-d6, 300 MHz) δ: 1.38 (9H,s); 1.88-2.0 (2H,m); 2.02 (3H,d); 2.62-2.75 (2H,m); 2.75-2.9 (2H,m); 4.32-4.42 (1H, m); 4.68 (2H,d); 5.83 (1H,m); 6.79-6.83 (2H,md); 6.95-7.1 (3H,m); 7.1-7.28 (4H,m); 7.45-7.52 (2H,dd); 7.61 (1H,s); 7.68 (1H,s); 8.62 (1H,t); 9.08 (1H,s). MS (ES+) m/z 636.4 (MH+); Anal.calculated for C35H39F2N3O4S.2.7H2O C, 61.4; H, 6.5; N, 6.1%; Found: C, 61.1; H, 6.2; N, 5.7%.

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

Procedure: The title compound was prepared from 2-(4-fluorophenyl)4-[1-(thiazol-2-yl)-2-(imidazol-1-yl)ethoxymethyl]benzoic acid by a similar method to that used for Example 1 but using L-methionine tert-butyl ester in place of L-methionine methyl ester.

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

Procedure: A solution of pentafluorophenyl 5-[(E)-3-(imidazol-1-yl)prop-1-en-1-yl]-2-(4-fluorophenethyl)benzoate (0.36 g, 0.7 mmol), L-methionine-tert-butyl ester(0.173 g, 0.84 mmol) and 1-hydroxy-7-azabenzotriazole (0.1 g, 0.73 mmol) in DMF (2 ml) was stirred at ambient temperature overnight. After evaporation of the solvent, the residue was taken up in ethyl acetate, washed with 5% sodium hydrogen carbonate solution and saturated brine and evaporated to dryness. The residue was then purified by flash chromatography eluting with dichloromethane/ethanol (97/3) to give the title compound. Yield: 50% After evaporation of the solvent washed with 5% sodium hydrogen carbonate solution and saturated brine evaporated to dryness The residue was then purified by flash chromatography eluting with dichloromethane/ethanol (97/3)