Reacción #61741

Ecuación de reacción

HOBt

1-(N,N-dimethylaminopropyl)piperazine

4-{4-[4-(Tetrahydropyran-4-sulfonyl)-phenyl]pyrimidin-2-ylamino}benzoic acid

4-{4-[4-(tetrahydro-pyran-4-sulfonyl)-phenyl]-pyrimidin-2-ylamino}-benzoic acid

EDCI

→

[4-(3-dimethylamino-propyl)piperazin 1-yl]-(4-{4-[4-(tetrahydropyran-4-sulfonyl)phenyl]pyrimidin-2-ylamino}phenyl)methanone

Rendimiento 22.2%

Disolventes

CH2Cl2

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Lavadowashed with 2% NaOH (aq, 30 mL), water (30 mL)
2. 2
   SecadoThe organic layer was dried (Na2SO4)
3. 3
   Filtraciónfiltered
4. 4
   Concentraciónconcentrated
5. 5
   Otrowas subjected to preparative HPLC (20-70 acetonitrile/water gradient, 20 min)
6. 6
   ConcentraciónThe desired fractions were concentrated
7. 7
   Otroto remove most of the acetonitrile
8. 8
   Extracciónthe aqueous mixture was extracted with CH2Cl2/2% NaOH (aq)
9. 9
   SecadoThe organic layer was dried (Na2SO4)
10. 10
    Filtraciónfiltered
11. 11
    Concentraciónconcentrated

Procedimiento

4-{4-[4-(Tetrahydropyran-4-sulfonyl)-phenyl]pyrimidin-2-ylamino}benzoic acid 4 (0.26 g, 0.6 mmol) was dissolved in THF (5 mL). To this solution was added 1-(N,N-dimethylaminopropyl)piperazine (0.130 g). EDCI (0.136 g), and HOBt (0.096 g). The mixture was stirred 12 h. The mixture was then diluted with CH2Cl2 (20 mL) and washed with 2% NaOH (aq, 30 mL), water (30 mL), and then brine (30 mL). The organic layer was dried (Na2SO4), filtered, and concentrated. The crude solid was subjected to preparative HPLC (20-70 acetonitrile/water gradient, 20 min). The desired fractions were concentrated to remove most of the acetonitrile, and then the aqueous mixture was extracted with CH2Cl2/2% NaOH (aq). The organic layer was dried (Na2SO4), filtered, and concentrated to afford [4-(3-dimethylamino-propyl)piperazin 1-yl]-(4-{4-[4-(tetrahydropyran-4-sulfonyl)phenyl]pyrimidin-2-ylamino}phenyl)methanone 5 (0.079 g; 22%): HPLC Retention Time; 7.93 min. (Method B) M+1=593.3

Fuente