Reaktion #166299

Reaktionsgleichung

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

Ausbeute 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

Ausbeute 57.7%

Lösungsmittel

toluene

water

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThis mixture was degassed
2. 2
   Sonstigeby bubbling nitrogen through this solution for ˜2 min
3. 3
   Temperaturwas heated overnight at 100° C
4. 4
   TemperaturThe reaction was cooled to 20° C.
5. 5
   SonstigeThe layers were partitioned
6. 6
   Waschenthe aqueous layer was washed with ethyl acetate
7. 7
   TrocknenThe combined organic fractions were dried over MgSO4
8. 8
   Einengenconcentrated
9. 9
   SonstigeThe product was purified by flash column chromatography
10. 10
    Wascheneluting with a gradient of DCM-6% methanol/0.3% NH4OH/DCM

Vorschrift

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.

Quelle