Chloroacetyl chloride → HCID 87546374, compound

Participants

Reaction Steps

A mixture of EXAMPLE 191A (600 mg, 1.46 mmol), N-BOC-ethylenediamine (469 mg, 2.93 mmol) and DIEA (189 mg, 1.46 mmol) was refluxed in ethanol (10 mL) for 3 h. The solvent was evaporated and the residue was flash chromatographed on SiO2 eluting with 10% methanol in DCM affording 265 mg (38%) intermediate tert-butyl 2-{[2-(2-{[(3-chloro-2-methylphenyl)sulfonyl]amino}-1,3-thiazol-4-yl)ethyl]amino}ethylcarbamate. This material (255 mg, 0.54 mmol) was dissolved in DCM (4 mL), followed by the addition of DMAP (163 mg, 1.21 mmol). Chloroacetyl chloride (134 mg, 1.18 mmol) dissolved in DCM (2 mL) was added, and the mixture was stirred for 1 h at room temperature followed by a wash with aqueous HCl (2 M). The remaining organic phase was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was taken up in ethyl acetate (25 mL), and at 0° C. HCl gas was bubbled trough under a period of 3 minutes. The mixture was stirred for 10 minutes and the solvent was evaporated giving 284 mg of N-(2-aminoethyl)-2-chloro-N-[2-(2-{[(3-chloro-2-methylphenyl)sulfonyl]amino}-1,3-thiazol-4-yl)ethyl]acetamide hydrochloride. This material (280 mg, 0.57 mmol) and sodium bicarbonate (169 mg, 2.01 mmol) were refluxed in ethanol (30 mL) for 2 h. The solvent was evaporated and the residue was flash chromatographed on RP silica gel gradient eluting with (acetonitrile in H2O/1% conc. HCl) giving 113 mg (47%) of 3-chloro-2-methyl-N-{4-[2-(2-oxo-1-piperazinyl)ethyl]-1,3-thiazol-2-yl}benzenesulfonamide hydrochloride.

Provenance & Evidence