Reacción #963607

Ecuación de reacción

Triethylamine

(2S,4S)-4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid

EDCI

HOBT

Dimethyl hydroxylamine HCl

→

product

Rendimiento 70.0%

(2S,4S)-tert-butyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-2-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

Rendimiento 70.0%

Disolventes

EtOAc

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe mixture was warmed to ambient temperature
2. 2
   workup.STIRRINGstirred for 4.5 hours
3. 3
   Lavadowashed with 1N KHSO4 (2×10 mL)
4. 4
   SecadoThe organic layer was dried over Na2SO4
5. 5
   Filtraciónfiltered
6. 6
   Concentraciónconcentrated
7. 7
   OtroThe crude material was purified by column chromatography (1 to 5% MeOH/CH2Cl2)

Procedimiento

(2S,4S)-4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid (Example 53; 0.100 g, 0.204 mmol), EDCI (0.0548 g, 0.286 mmol) and HOBT (0.0359 g, 0.266 mmol) were mixed in CH2Cl2 (2.5 mL) and the mixture was cooled to 0° C. Triethylamine (0.0712 mL, 0.511 mmol) was added and the mixture was stirred for 15 minutes. Dimethyl hydroxylamine HCl (0.0299 g, 0.306 mmol) was added, and the mixture was warmed to ambient temperature and stirred for 4.5 hours. The mixture was diluted with EtOAc (20 mL) and washed with 1N KHSO4 (2×10 mL), followed by a saturated aqueous NaHCO3 solution and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by column chromatography (1 to 5% MeOH/CH2Cl2) to provide 0.076 g (70%) of the product as a white foam.

Fuente