tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-(4-(pyrrolidin-1-yl)quinazolin-7-yl)piperazine-1-carboxylate

Temperatur

100 °C

Potassium tert-butoxide (998 mg, 8.99 mmol), 2-dicyclohexylphosphino-2,4,6-triisopropyl-biphenyl (X-Phos) (79 mg, 0.18 mmol) and tris-(dibenzylideneacetone)-dipalladium [Pd2(dba)3] (36 mg, 0.036 mmol) were added, under nitrogen, to a mixture of 7-chloro-4-(pyrrolidin-1-yl)quinazoline (A) (840 mg, 3.59 mmol) and tert-butyl piperazine-1-carboxylate (1.0 g, 5.39 mmol) in toluene (49 ml). The reaction mixture was then heated for 15 h at 100° C. The reaction mixture was cooled to room temperature, and water (25 ml) and ethyl acetate (25 ml) were added. The aqueous phase was extracted with ethyl acetate (2×25 ml), and the combined organic phases were washed with saturated sodium chloride solution (20 ml). The organic phase was then dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel) using ethyl acetate/-dichloromethane/ammonia solution (25% aq.) (50:10:0.5) and ethyl acetate/dichloro-methane/methyl tert-butyl ether/ammonia solution (25% aq.) (50:10:10:0.7).

1. temperatureThe reaction mixture was cooled to room temperature
2. extractionThe aqueous phase was extracted with ethyl acetate (2×25 ml)
3. washthe combined organic phases were washed with saturated sodium chloride solution (20 ml)
4. dry with materialThe organic phase was then dried (MgSO4)
5. concentrationconcentrated in vacuo
6. customThe crude product was purified by column chromatography (silica gel)

ORD-Eintrag

ord-21ec4c1f22c14a65a569bc67b5d27e3f

Quelldatensatz

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08435978B2