Tebipenem

Tebipenem is an orally available carbapenem antibiotic, shows broad-spectrum activity against Gram-positive and -negative bacteria, except for Pseudomonas aeruginosa.

The compound (II) (R is p-nitrobenzyl) (15.0 g, 29.Ommo 1) was added 200 mL of n-butanol, 200 mL of water, stirred to dissolve, and 8.00 g of Raney Ni was added and hydrogenated at 20 ° C under 2.0 MPa hydrogen pressure for 4 h. The filter cake was washed with 15 mL of water The filtrate was adjusted to pH 6.5 with 4-dimethylaminopyridine and then washed with 150 mL of ethyl acetate. After cooling to 0 ° C, 700 mL of acetone was added dropwise, stirred for 10 min and then 700 mL of acetone was added dropwise, stirred for 1 h, To give telbemidine as a white solid 12.5 g, yield 94.5percent, purity 99.6percent.The 229.2 g of the intermediate I obtained in was successively mixed with 27.4 g of the volume of n-butanol aqueous solution (3: 1 volume of n-butanol and water), 27.4 g of palladium-carbon catalyst (0.5percent palladium), and 330.0 g of sodium bicarbonate. The reaction was carried out for 3 hours at a hydrogen pressure of 1MPa, temperature 25 to 30 ° C and a rotation speed of 500 r / min. After the completion of the reaction, the suction filtration was carried out and the filtrate pH was adjusted to 5.5 with 4mo 1/1 hydrochloric acid to give an aqueous phase and n-butanol phase; Cooling to 7 to 8 ° C, while stirring the aqueous phase slowly added 5 times its volume of acetone, the solution crystallization, filtration, drying was carried out to obtain the intermediate II 151.3g, the calculated yield was 89.3percent and the purity was 99.5percent.The compound (II) (R is p-nitrobenzyl) (15.0 g, 29.Ommo 1) was added 200 mL of n-butanol, 200 mL of water, stirred to dissolve, and 8.00 g of Raney Ni was added and hydrogenated at 20 ° C under 2.0 MPa hydrogen pressure for 4 h. The filter cake was washed with 15 mL of water The filtrate was adjusted to pH 6.5 with 4-dimethylaminopyridine and then washed with 150 mL of ethyl acetate. After cooling to 0 ° C, 700 mL of acetone was added dropwise, stirred for 10 min and then 700 mL of acetone was added dropwise, stirred for 1 h, To give telbemidine as a white solid 12.5 g, yield 94.5percent, purity 99.6percent.The 229.2 g of the intermediate I obtained in was successively mixed with 27.4 g of the volume of n-butanol aqueous solution (3: 1 volume of n-butanol and water), 27.4 g of palladium-carbon catalyst (0.5percent palladium), and 330.0 g of sodium bicarbonate. The reaction was carried out for 3 hours at a hydrogen pressure of 1MPa, temperature 25 to 30 ° C and a rotation speed of 500 r / min. After the completion of the reaction, the suction filtration was carried out and the filtrate pH was adjusted to 5.5 with 4mo 1/1 hydrochloric acid to give an aqueous phase and n-butanol phase; Cooling to 7 to 8 ° C, while stirring the aqueous phase slowly added 5 times its volume of acetone, the solution crystallization, filtration, drying was carried out to obtain the intermediate II 151.3g, the calculated yield was 89.3percent and the purity was 99.5percent.

Molecular Weight:383.5
XLogP3:0.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:5
Exact Mass:383.09734851
Monoisotopic Mass:383.09734851
Topological Polar Surface Area:144
Heavy Atom Count:25
Complexity:689
Defined Atom Stereocenter Count:4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes