Methylamine → HCID 66864635, compound

Participants

Reaction Conditions

Reaction Steps

60 mg of 1-hydroxybenzotriazole, 200 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 0.700 cm3 of a 2M solution of methylamine in tetrahydrofuran, 0.370 cm3 of triethylamine and 8 cm3 of tetrahydrofuran are added successively to a solution of 0.5 g of (S)-2-[3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}methanesulphonylamino)benzoyl-amino]propionic acid in 15 cm3 of tetrahydrofuran, stirred at a temperature in the region of 20° C. under an inert atmosphere. The reaction medium is stirred at a temperature in the region of 20° C. for 18 hours. After concentration to dryness under reduced pressure, the residue is dissolved in a mixture consisting of 30/15 cm3 of dichloromethane/water. After separation by settling out, the aqueous phase is extracted twice with 15 cm3 of dichloromethane. The organic phases are combined, washed with 15 cm3 of a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and then concentrated to dryness, to give 0.415 g of a crude product which is purified by flash chromatography on a Merck 25 g silica cartridge (particle size: 15-40 μm; eluent: 100 ethyl acetate). After concentration of the fractions under reduced pressure, 0.293 g of a product is obtained which is triturated in a minimum amount of pentane. After filtration, concentration to dryness under reduced pressure and drying, 0.247 g of a solid cream is obtained. 147 mg of this solid cream are injected onto a column 6 cm in diameter containing 700 g of Chiralpak IA 20 μM chiral stationary phase. The elution is carried out at 80 cm3 per minute with a mobile phase composed of 95% acetonitrile and 5% dichloromethane. The dextrorotatory enantiomer is eluted in the second position. After concentration of the mobile phase, 105 mg of 3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}methanesulphonylamino)-N—((S)-1-methyl-carbamoylethyl)benzamide are obtained in the form of an amorphous white powder.

Provenance & Evidence