Oxalyl chloride → 2-{[6-(4-Fluoro-phenyl)-5-piperidin-1-yl-pyrazine-2-carbonyl]-amino}-2-methyl-propionic acid methyl ester

To a dichloromethane (1 ml) solution of 6-(4-Fluoro-phenyl)-5-piperidin-1-yl-pyrazine-2-carboxylic acid (0.107 g, 0.358 mmol, 1.0 eq) was added oxalyl chloride (0.136 g, 1.07 mmol, 3.0 eq). The reaction was stirred at room temperature for 3 hours after which time the solvent was removed in vacuo. The residue was re-dissolved in dichloromethane (3 ml) and added portion-wise to a dichloromethane (1 ml) solution of aminoisobutyric acid methyl ester (0.066 g, 0.429 mmol, 1.2 eq). PS-N,N-diisopropyl-ethylamine (0.31 g, 1.04 mmol, 3.0 eq) resin was added to the reaction and the mixture stirred overnight at room temperature. PS-isocyanate (0.15 g, 0.358 mmol, 1.0 eq) and PS-aminomethyl (0.15 g, 0.358 mmol, 1.0 eq) resin were added to the reaction and the mixture stirred for a further 12 hrs at room temperature. The reaction was filtered and resin washed successfully with dichloromethane (2×3 ml). The combined filtrates were concentrated in vacuo and the residue purified by chromatography on silica gel with heptane:ethyl acetate (1:1) to afford 2-{[6-(4-fluoro-phenyl)-5-piperidin-1-yl-pyrazine-2-carbonyl]-amino}-2-methyl-propionic acid methyl ester. Yield=0.030 g (21%). HPLC-MS 100%; 2.52 min (MW=400; M+1=401.2).

1. customwas removed in vacuo
2. dissolutionThe residue was re-dissolved in dichloromethane (3 ml)
3. stirringthe mixture stirred overnight at room temperature
4. stirringthe mixture stirred for a further 12 hrs at room temperature
5. filtrationThe reaction was filtered
6. washresin washed successfully with dichloromethane (2×3 ml)
7. concentrationThe combined filtrates were concentrated in vacuo
8. customthe residue purified by chromatography on silica gel with heptane:ethyl acetate (1:1)

ORDレコード

ord-ca674d20f89f42fb96faf94d8da9d714

出典データセット

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07812028B2