Oxalyl chloride → N-(3-tert-butyl-isoxazol-5-ylmethyl)-2-methyl-2-(tetrahydro-pyran-4-sulfonyl)-propionamide

Activation of 51 mg (0.22 mmol) of 2-methyl-2-(tetrahydro-pyran-4-sulfonyl)-propionic acid as the corresponding acid chloride is achieved by treatment with oxalyl chloride (0.04 mL) and DMF (1 drop) in DCM (2 mL) at room temperature for 1 h. The reaction is concentrated under reduced pressure. The crude acid chloride is dissolved in DCM (1 mL) and added dropwise to a solution of (3-tert-butyl-1,2-oxazol-5-yl)methanamine (42 mg, 80%, 0.22 mmol) and N,N-diisopropylethylamine (114 μL, 0.66 mmol) in DCM (2 mL). The reaction is concentrated under reduced pressure. The residue is purified twice by column chromatography (silica, eluent: heptanes, 0-50% ethyl acetate then DCM, 20% ethyl acetate), followed by preparative HPLC (neutral method) to give 36 mg of N-(3-tert-butyl-isoxazol-5-ylmethyl)-2-methyl-2-(tetrahydro-pyran-4-sulfonyl)-propionamide. Yield: 44%; ES-MS: m/z 373 [M+H]. Compounds in Table 4 amide method D are made according to this procedure.

1. concentrationThe reaction is concentrated under reduced pressure
2. dissolutionThe crude acid chloride is dissolved in DCM (1 mL)
3. concentrationThe reaction is concentrated under reduced pressure
4. customThe residue is purified twice by column chromatography (silica, eluent

ORDレコード

ord-444e031952944cbea500f1087f426aeb

出典データセット

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09315454B2