H-Thr-NH2 HCl

Chemical Properties

White solid

Uses

L-Threonine Amide Hydrochloride is used as a reagent in the synthesis of N-monosubstituted [(pyridin-2-yl)methyl]amine and [(pyrimidin-4-yl)methyl]amine derivatives as transient receptor potential cation channel 3 (TRPV3) modulators.

Synthesis

The general procedure for the synthesis of (2S,3R)-2-amino-3-hydroxy-1-oxobutan-2-yl)carbamic acid benzyl ester from (2S,3R)-1-amino-3-hydroxybutyramide hydrochloride is as follows: dissolve N-Cbz-ThrNH2 (504 g, 2 mol) in methanol, followed by addition of 10% Pd/C catalyst (50.4 g, 10 wt%) . The resulting suspension was stirred in hydrogen (1.0 MPa) atmosphere for 12 h at room temperature. Upon completion of the reaction, the Pd/C catalyst was removed by filtration, and the filtrate was evaporated under vacuum to obtain a crude product in the form of a yellow oil. This crude product was redissolved in 3 L of acetone, and HCl solution dissolved in isopropanol (500 mL) was added slowly at 0-5 °C while stirring. The precipitated white solid was collected by filtration and dried under high vacuum (45 °C, 0.1 MPa) to give the final target product 1b 289 g (93.5% yield). The product was analyzed by 1H-NMR (400 MHz, D2O) showing δ 4.15 (p, J = 6.1 Hz, 1H), 3.86 (d, J = 5.2 Hz, 1H), 1.25 (d, J = 6.5 Hz, 3H); and 13C-NMR (101 MHz, D2O) analysis showing δ 170.25, 66.04, 58.40, 18.80. HRMS (ESI-TOF+) analysis showed m/z ([M + H]+) calculated value of 119.0815 (corresponding to C14H11N2O2 + H+) and measured value of 119.0817.

References

[1] Molecules, 2018, vol. 23, # 5,