Реакция #163992

ord-84bb71aa225b41fe8bf187851ad05c28

Уравнение реакции

COc1c(N2CCCCC2=O)cc(F)cc1S(=O)(=O)N[C@@H](Cc1cc(-c2ccc(Cl)s2)on1)C(=O)O
Intermediate 17
COc1c(N2CCCCC2=O)cc(F)cc1S(=O)(=O)N[C@@H](Cc1cc(-c2ccc(Cl)s2)on1)C(=O)O
(S)-3-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-yl]-2-[5-fluoro-2-methoxy-3-(2-oxo-piperidin-1-yl)-benzenesulfonylamino]-propionic acid
CNC1CC1
cyclopropyl-methylamine
CCOC(=O)C(C#N)=NOC(N(C)C)=[N+](C)C.F[B-](F)(F)F
TOTU
→
COc1c(N2CCCCC2=O)cc(F)cc1S(=O)(=O)N[C@@H](Cc1cc(-c2ccc(Cl)s2)on1)C(=O)NCC1CC1
(S)-3-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-yl]-N-cyclopropylmethyl-2-[5-fluoro-2-methoxy-3-(2-oxo-piperidin-1-yl)-benzenesulfonylamino]-propionamide

Реактанты

COc1c(N2CCCCC2=O)cc(F)cc1S(=O)(=O)N[C@@H](Cc1cc(-c2ccc(Cl)s2)on1)C(=O)O
Intermediate 17
COc1c(N2CCCCC2=O)cc(F)cc1S(=O)(=O)N[C@@H](Cc1cc(-c2ccc(Cl)s2)on1)C(=O)O
(S)-3-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-yl]-2-[5-fluoro-2-methoxy-3-(2-oxo-piperidin-1-yl)-benzenesulfonylamino]-propionic acid
CNC1CC1
cyclopropyl-methylamine
CCOC(=O)C(C#N)=NOC(N(C)C)=[N+](C)C.F[B-](F)(F)F
TOTU

Реагенты

Нет

Условия реакции

Температура
50°CELSIUS
Подробные условия
See reaction.notes.procedure_details.

Обработка

  1. 1
    ДругоеThe mixture was purified by preparative HPLC
  2. 2
    ДругоеYield after lyophilization

Методика

Intermediate 17 (350 mg, 0.63 mmol) and cyclopropyl-methylamine (45 mg, 0.63 mmol) were coupled using the procedure described in example 1; 1.9), where only 25% conversion of starting materials was discovered. Heating to 50° C. did not lead to further conversion. Then TOTU (246 mg, 0.75 mmol) was added and after stirring for 1 h at RT conversion was completed. The mixture was purified by preparative HPLC. Yield after lyophilization: 162 mg, 43%, colorless, amorphous solid.

Источник

DOI: 10.6084/m9.figshare.5104873.v1Патент: US08835653B2uspto-grants-2014_09