Reacción #509063

Ecuación de reacción

O-Cyclopropylmethyl-hydroxylamine

2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid

EDCI

HOBt

Et3N

→

pure desired product

Rendimiento 57.1%

2-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid cyclopropylmethoxyamide

Rendimiento 57.1%

Disolventes

EtOAc

DMA

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGAfter the reaction mixture was stirred for 16 hours at room temperature
2. 2
   Lavadowashed with saturated NH4Cl solution, saturated NaHCO3 solution and saturated NaCl
3. 3
   SecadoThe organic layer was dried (Na2SO4)
4. 4
   Concentraciónconcentrated under reduced pressure
5. 5
   OtroPurification by flash column chromatography (methylene chloride/methanol, 20:1)

Procedimiento

A mixture of 2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (0.022 g, 0.064 mmol), EDCI (0.019 g, 0.097 mmol), and HOBt (0.019 g, 0.097 mmol) in DMA (1 mL) was stirred for 30 minutes at room temperature under N2. O-Cyclopropylmethyl-hydroxylamine (0.017 g, 0.19 mmol) was added followed by Et3N (0.022 mL, 0.016 g, 0.16 mmol). After the reaction mixture was stirred for 16 hours at room temperature, it was diluted with EtOAc and washed with saturated NH4Cl solution, saturated NaHCO3 solution and saturated NaCl. The organic layer was dried (Na2SO4) and concentrated under reduced pressure. Purification by flash column chromatography (methylene chloride/methanol, 20:1) gave 0.015 g (57%) pure desired product as a yellow solid. MS APCI (−) m/z 410, 411 (M−, Br pattern) detected; 1H NMR (400 MHz, DMSO-d6) δ 11.4 (s, 1H), 9.81 (s, 1H), 7.58 (m, 2H), 7.28 (d, 1H), 6.82 (t, 1H), 6.17 (d, 1H), 3.46 (d, 2H), 3.22 (s, 3H), 0.99 (m, 1H), 0.48 (m, 2H), 0.18 (m, 2H).

Fuente