Reacción #2292790

Ecuación de reacción

2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile

tert-butyl (R)-4-(5-((S)-1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-2-methylpiperazine-1-carboxylate

triethylamine

2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile

Triethylamine

→

title compound

Rendimiento 84.1%

tert-Butyl (R)-4-(5-((S)-1-((2-amino-5-cyano-6-methylpyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-2-methylpiperazine-1-carboxylate

Rendimiento 84.1%

Disolventes

DMSO

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe mixture was heated for another 3 hours at 80° C
2. 2
   OtroThe cooled mixture was partitioned between saturated NaHCO3 and ethyl acetate
3. 3
   ExtracciónThe aqueous layer was extracted with ethyl acetate
4. 4
   Secadodried over MgSO4
5. 5
   Filtraciónfiltered
6. 6
   Concentraciónconcentrated
7. 7
   OtroThe residue was purified by liquid chromatography (SiO2, 25-100% EtOAc/heptanes gradient)

Procedimiento

To a 50 mL pear flask were added 2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile (30.5 mg, 0.181 mmol) and tert-butyl (R)-4-(5-((S)-1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-2-methylpiperazine-1-carboxylate (45 mg, 0.120 mmol) in DMSO (0.60 mL). Triethylamine (84 μL, 0.60 mmol) was added, and the mixture was stirred at 80° C. for 2 hours. Additional triethylamine (84 μL, 0.602 mmol) and 2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile (10 mg, 0.060 mmol) were added and the mixture was heated for another 3 hours at 80° C. The cooled mixture was partitioned between saturated NaHCO3 and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over MgSO4, filtered, and concentrated. The residue was purified by liquid chromatography (SiO2, 25-100% EtOAc/heptanes gradient) to give the title compound as a white solid (51 mg, 84%). 1H NMR (400 MHz, CDCl3) δ ppm 1.48-1.52 (m, 12H), 1.54 (d, J=6.82 Hz, 3H), 2.39 (s, 3H), 2.79-2.86 (m, 1H), 2.89-3.09 (m, 3H), 3.35 (br s, 1H), 3.78 (s, 3H), 4.05 (d, J=9.85 Hz, 1H), 4.34 (br s, 1H), 5.27 (br s, 1H), 5.94 (quin, J=6.76 Hz, 1H), 6.66 (d, J=3.28 Hz, 1H), 7.24 (d, J=3.28 Hz, 1H), 7.31 (d, J=7.83 Hz, 1H), 7.40 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C26H35N9O2, 506. found 506.

Fuente