Toluene → HCID 69593066, compound

Participants

Reaction Steps

2-[1-carboxy-2-(1phenyl-1H-pyrazol-3-yl)-ethylamino]-4-methyl-pentanoic acid Phenyl pyrazole 54-3 was prepared as described by R. M. Adlington et al. from 54-1 (J. Chem. Soc. Perkin Trans I 2000, 2311–2316). This reaction with phenyl hydrazine provided a single isomer whose structure was confirmed with 2D NMR methods (NOESY, HMBC, and HMQC). Phenyl pyrazole 54-3 (380 mg, 0.98 mmol) was dissolved in dichloromethane (4 mL) and a solution of HCl (2.45 mL, 9.80 mmol, 4 N in dioxane) was added dropwise. The resulting mixture was stirred for 2 hours at room temperature, and a precipitate formed. The reaction mixture was concentrated to give a brown oil (290 mg, 100% yield). 1H NMR was consistent with the desired amino acid (with some tert-butyl ester). This oil was dissolved in methanol (5 mL) and toluene (5 mL) and a solution of trimethylsilyldiazomethane (2 mL, 3.92 mmol, 2 M in hexane) was added (gas evolution and precipitate formation). After 2 hours, the reaction mixture was concentrated to a brown oil. This oil was redissolved in ethyl acetate and the solution was extracted with saturated NaHCO3 solution, dried over Na2SO4, filtered and concentrated to give 2-amino-3-(1-phenyl-1H-pyrazol-3-yl)-propionic acid methyl ester (54-4) as a brown oil (262 mg, >100% yield, contaminated with some tert-butyl ester). This ester was alkylated with triflate 54-5 as described above. The resulting diester was hydrolyzed to 2-[1-carboxy-2-(1phenyl-1H-pyrazol-3-yl)-ethylamino]-4-methyl-pentanoic acid 54-6 (Compound OD) as described above. 1H NMR (300 MHz, CD3OD) δ 8.17 (d, 1H, J=2.4 Hz); 7.76 (d, 2H, J=7.7 Hz); 7.46 (dd, 2H, J1=7.7 Hz, J2=8.1 Hz); 7.30 (t, 1H, J=7.3 Hz); 6.45 (d, 1H, J=2.4 Hz); 4.08 (dd, 1H, J1=4.5 Hz, J2=7.3 Hz); 3.97 (dd, 1H, J1=J2=6.9 Hz); 3.43 (dd, 1H, J1=4.7 Hz, J2=16.1 Hz); 3.34 (dd, 1H, J1=7.3 Hz, J2=16.3 Hz); 1.90–1.98 (m, 1H); 1.78–1.84 (m, 2H); 1.01 (d, 3H, J=5.3 Hz); 0.99 (d, 3H, J=5.7 Hz). Anal. Calc'd. for C18H23N3O4.H2O: % C, 59.49; % H 6.93; % N, 11.56. Found: % C, 59.85; % H, 6.96; and % N, 11.46.

Provenance & Evidence