Reacción #44964

Ecuación de reacción

N-(5-Chloropyridin-2-yl)-3-({[trans-4-(methylamino)-cyclohexyl]carbonyl}amino)furo[3,2-b]pyridine-2-carboxamide trihydrochloride

sodium hydrogen carbonate

3-aminopropionaldehyde diethyl acetal

sodium triacetoxy borohydride

3-t-butoxycarbonyl-aminopropanal

→

title compound

t-Butyl {3-[(trans-4-{[(2-{[(5-chloropyridin-2-yl)amino]-carbonyl}furo[3,2-b]pyridin-3-yl)amino]carbonyl}cyclohexyl)(methyl)-amino]propyl}carbamate

Disolventes

chloroform

triethylamine

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturacooling
2. 2
   workup.STIRRINGstirred for 2 hours
3. 3
   Temperaturacooling
4. 4
   Extracciónthe mixture is extracted with chloroform
5. 5
   LavadoThe organic layer is washed successively with water and saturated brine
6. 6
   Secadodried over sodium sulfate
7. 7
   Otrothe solvent is evaporated under reduced pressure
8. 8
   OtroThe resulting residue is purified by NH-silica gel column chromatography (eluent: ethyl acetate followed by ethyl acetate/methanol=20/1)

Procedimiento

N-(5-Chloropyridin-2-yl)-3-({[trans-4-(methylamino)-cyclohexyl]carbonyl}amino)furo[3,2-b]pyridine-2-carboxamide trihydrochloride (300 mg) obtained in Example 119 is suspended in chloroform (7 ml). To the suspension are added 3-t-butoxycarbonyl-aminopropanal (208 mg), which can be prepared from 3-aminopropionaldehyde diethyl acetal in two steps according to the method described in a literature (Synthesis, 1994, 37) and triethylamine (334 μl) under ice-cooling, and the mixture is stirred for a few minutes. After addition of sodium triacetoxy borohydride (190 mg), the reaction solution is warmed to room temperature and stirred for 2 hours. To the reaction solution is poured saturated aqueous sodium hydrogen carbonate solution under ice-cooling, and the mixture is extracted with chloroform. The organic layer is washed successively with water and saturated brine, dried over sodium sulfate, and the solvent is evaporated under reduced pressure. The resulting residue is purified by NH-silica gel column chromatography (eluent: ethyl acetate followed by ethyl acetate/methanol=20/1) to give the title compound (291 mg).

Fuente