Reacción #155416

ord-62f5b10b7d794c21bde5c1df8ca5fed7

Ecuación de reacción

CCN(CC)CC
Triethylamine
O=C1S[C@H]2C[C@@H]1N(C(=O)OCc1ccc([N+](=O)[O-])cc1)C2
Intermediate 1
O=C1S[C@H]2C[C@@H]1N(C(=O)OCc1ccc([N+](=O)[O-])cc1)C2
(1S,4S)-4-nitrobenzyl 3-oxo-2-thia-5-azabicylco[2.2.1]heptane-5-carboxylate
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CN[C@H](C(=O)NCc4ccc(S(N)(=O)=O)cc4)C3)[C@H](C)[C@H]12
(4R,5S,6S)-4nitrobenzyl 6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-3-(((3S,5S)-5-((4-sulfamoylbenzyl)carbamoyl)pyrrolidin-3-yl)thio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CN[C@H](C(=O)NCc4ccc(S(N)(=O)=O)cc4)C3)[C@H](C)[C@H]12
raw material 3
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CN[C@H](C(=O)NCc4ccc(S(N)(=O)=O)cc4)C3)[C@H](C)[C@H]12
(4R,5S,6S)-4nitrobenzyl 6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-3-(((3S,5S)-5-((4-sulfamoylbenzyl)carbamoyl)pyrrolidin-3-yl)thio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
CCOC(C)=O
ethyl acetate
→
CC(=O)O.NCc1ccc(S(N)(=O)=O)cc1
solid
CC(=O)O.NCc1ccc(S(N)(=O)=O)cc1
mafenide acetate

Reactantes

CCN(CC)CC
Triethylamine
O=C1S[C@H]2C[C@@H]1N(C(=O)OCc1ccc([N+](=O)[O-])cc1)C2
Intermediate 1
O=C1S[C@H]2C[C@@H]1N(C(=O)OCc1ccc([N+](=O)[O-])cc1)C2
(1S,4S)-4-nitrobenzyl 3-oxo-2-thia-5-azabicylco[2.2.1]heptane-5-carboxylate
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CN[C@H](C(=O)NCc4ccc(S(N)(=O)=O)cc4)C3)[C@H](C)[C@H]12
(4R,5S,6S)-4nitrobenzyl 6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-3-(((3S,5S)-5-((4-sulfamoylbenzyl)carbamoyl)pyrrolidin-3-yl)thio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CN[C@H](C(=O)NCc4ccc(S(N)(=O)=O)cc4)C3)[C@H](C)[C@H]12
raw material 3
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@@H]3CN[C@H](C(=O)NCc4ccc(S(N)(=O)=O)cc4)C3)[C@H](C)[C@H]12
(4R,5S,6S)-4nitrobenzyl 6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-3-(((3S,5S)-5-((4-sulfamoylbenzyl)carbamoyl)pyrrolidin-3-yl)thio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
CCOC(C)=O
ethyl acetate

Reactivos

Ninguno

Disolventes

CN(C)C=O
dimethylformamide

Condiciones de reacción

Temperatura
-15°CELSIUS
Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    workup.ADDITIONwas added
  2. 2
    LavadoThe mixture was sequentially washed with water, dilute hydrochloric acid and saturated sodium bicarbonate
  3. 3
    Secadothe organic layer was dried over anhydrous sodium sulfate
  4. 4
    ConcentraciónThe ethyl acetate layer was concentrated
  5. 5
    Filtraciónthe precipitate was filtered
  6. 6
    Otrodried

Procedimiento

Intermediate 1 and (4R,5S,6S)-4nitrobenzyl 6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-3-(((3S,5S)-5-((4-sulfamoylbenzyl)carbamoyl)pyrrolidin-3-yl)thio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (raw material 3) (2980 g, 5.01 mol) were dissolved in dimethylformamide, and the solution was cooled to −15° C. Triethylamine was added dropwise under nitrogen protection. After the reaction is over, ethyl acetate was added. The mixture was sequentially washed with water, dilute hydrochloric acid and saturated sodium bicarbonate, and the organic layer was dried over anhydrous sodium sulfate. The ethyl acetate layer was concentrated and the precipitate was filtered, and dried to obtain 3300 g of a solid (i.e. intermediate 2) with a yield of 79.46% and a purity of 94.75%.

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US08822445B2uspto-grants-2014_09