Reacción #72603

Ecuación de reacción

N-ethyl-N-isopropylpropan-2-amine

3-(hydroxymethyl)pyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-6(5H)-one

N,3-dimethyl-4-(piperazin-1-yl)benzamide dihydrochloride

(cyanomethyl)trimethylphosphonium iodide

→

N,3-dimethyl-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamide

Rendimiento 39.7%

Disolventes

Propiononitrile

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe suspension was cooled to 23° C.
2. 2
   Concentraciónconcentrated via rotary evaporation, re-constituted in ACN (2.0 mL)
3. 3
   workup.STIRRINGstirred for 15 min
4. 4
   Filtraciónfiltered
5. 5
   Lavadorinsed with ACN (3×1 mL)
6. 6
   Otrodried in vacuo
7. 7
   Temperaturaheated
8. 8
   Temperaturato reflux
9. 9
   Temperaturacooled to 23° C.
10. 10
    Filtraciónfiltered
11. 11
    Lavadorinsed with ACN (3×2.0 mL)

Procedimiento

To a suspension of 3-(hydroxymethyl)pyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-6(5H)-one (75.00 mg, 0.348 mmol), N,3-dimethyl-4-(piperazin-1-yl)benzamide dihydrochloride (133 mg, 0.436 mmol) and (cyanomethyl)trimethylphosphonium iodide (136 mg, 0.558 mmol) in Propiononitrile (Volume: 2.00 mL) was added N-ethyl-N-isopropylpropan-2-amine (0.425 mL, 2.439 mmol) at 23° C. The reaction was stirred at 95° C. for 15 hr. The suspension was cooled to 23° C., concentrated via rotary evaporation, re-constituted in ACN (2.0 mL), stirred for 15 min, filtered, rinsed with ACN (3×1 mL) and dried in vacuo. The crude solid was re-suspended in ACN (2.0 mL), heated to reflux, cooled to 23° C., filtered, rinsed with ACN (3×2.0 mL) to provide N,3-dimethyl-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamide (0.0594 g, 0.138 mmol, 39.6% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.26 (s, 3 H) 2.53-2.66 (m, 4 H) 2.75 (d, J=4.55 Hz, 3 H) 2.86-2.96 (m, 4 H) 3.64 (s, 2 H) 6.71-6.76 (m, 1 H) 7.03 (d, J=8.34 Hz, 1 H) 7.07 (dd, J=3.66, 1.64 Hz, 1H) 7.58 (d, J=1.77 Hz, 1 H) 7.59-7.66 (m, 2 H) 7.67 (dd, J=3.03, 1.52 Hz, 1 H) 8.19 (q, J=4.29 Hz, 1 H) 8.36 (d, J=1.52 Hz, 1 H) 11.58 (s, 1 H). ESI-MS: m/z 431.4 (M+H)+. mp=264.0-266.3° C.

Fuente