Reacción #166299

Ecuación de reacción

Compound 4

9-Cyclopentyl-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-amine

compound 72

1,1-dimethylethyl 4-((2-bromo-1,3-thiazol-4-yl)carbonyl)-1-piperazinecarboxylate

compound 72

1,1-dimethylethyl 4-((2-bromo-1,3-thiazol-4-yl)carbonyl)-1-piperazinecarboxylate

t-Butyl-XPhos

sodium 2-methylpropan-2-olate

sodium 2-methylpropan-2-olate

t-Butyl-XPhos

→

compound 74

Rendimiento 57.7%

1,1-dimethylethyl 4-((2-((9-cyclopentyl-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-1,3-thiazol-4-yl)carbonyl)-1-piperazinecarboxylate

Rendimiento 57.7%

Disolventes

toluene

water

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThis mixture was degassed
2. 2
   Otroby bubbling nitrogen through this solution for ˜2 min
3. 3
   Temperaturawas heated overnight at 100° C
4. 4
   TemperaturaThe reaction was cooled to 20° C.
5. 5
   OtroThe layers were partitioned
6. 6
   Lavadothe aqueous layer was washed with ethyl acetate
7. 7
   SecadoThe combined organic fractions were dried over MgSO4
8. 8
   Concentraciónconcentrated
9. 9
   OtroThe product was purified by flash column chromatography
10. 10
    Lavadoeluting with a gradient of DCM-6% methanol/0.3% NH4OH/DCM

Procedimiento

Compound 4 (0.075 g, 0.30 mmol) was combined with sodium 2-methylpropan-2-olate (0.085 g, 0.89 mmol) and compound 72 (0.14 g, 0.38 mmol) in toluene (2 mL). This mixture was degassed by bubbling nitrogen through this solution for ˜2 min followed by the addition of Pd2(dba)3 (0.014 g, 0.015 mmol) and t-Butyl-XPhos (0.025 g, 0.059 mmol). The reaction was heated overnight at 60° C. Additional compound 72, 0.28 g, 0.76 mmol), Pd2(dba)3 (25 mg), t-Butyl-XPhos (54 mg), and the sodium 2-methylpropan-2-olate (0.085 g, 0.89 mmol) were added to the reaction which was heated overnight at 100° C. The reaction was cooled to 20° C. and poured into a separation funnel, with ethyl acetate and water. The layers were partitioned and the aqueous layer was washed with ethyl acetate. The combined organic fractions were dried over MgSO4 and concentrated. The product was purified by flash column chromatography, eluting with a gradient of DCM-6% methanol/0.3% NH4OH/DCM to yield compound 74 (95 mg) as a brown film. LCMS-ESI (POS), M/Z, M+1: Found 549.3.

Fuente