4-Aminomethyltetrahydropyran → 6-Bromo-3-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine

Temperatur

80 °C

To a scintillation vial containing 3,5-dibromo-2-chloropyrazine (1 g, 3.67 mmol) and TEA (1.024 ml, 7.34 mmol) was added MeCN (5 ml) and (tetrahydro-2H-pyran-4-yl)methanamine (0.557 g, 3.67 mmol). The homogenous reaction mixture was capped, and heated to 80° C. in a oil bath for 4 hr. The reaction mixture was concentrated to dryness, diluted with EtOAc and sequentially washed with sat NaHCO3, and sat NaCl. The organic layer was dried Na2SO4, filtered and concentrated. The crude was purified by column chromatography on silica gel (20% EtOAc/Hexane) to yield 6-bromo-3-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (688 mg, 2.244 mmol, 61.1% yield), yield), LCMS (m/z): 308.0 (MH+), retention time=0.94 min, and 6-bromo-5-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (55 mg, 0.179 mmol, 4.89% yield), LCMS (m/z): 308.0 (MH+), retention time=0.91 min.

1. customThe homogenous reaction mixture was capped
2. concentrationThe reaction mixture was concentrated to dryness
3. additiondiluted with EtOAc
4. washsequentially washed with sat NaHCO3
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude was purified by column chromatography on silica gel (20% EtOAc/Hexane)

ORD-Eintrag

ord-e940e6cdfc8e4cea8744fb038615e0ee

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08778951B2