1,2-Dimethoxyethane → 5-(3,6-dihydro-2H-pyran-4-yl)pyrazin-2-amine

HRID 595785Notes

Reaction equation

Br[C:2]1[N:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.CO[CH2:11][CH2:12][O:13][CH3:14].C([O-])([O-])=O.[Na+].[Na+].[CH3:21][CH2:22]OC(C)=O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:13]1[CH2:14][CH:22]=[C:21]([C:2]2[N:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=2)[CH2:11][CH2:12]1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of boronic ester (6.64 g, 31.6 mmol), 5-bromopyrazin-2-amine (5 g, 28.7 mmol), and PdCl2(dppf) (2.1 g, 2.87 mmol) was added DME (71.8 mL) and 2 M Na2CO3 solution (24 mL). The reaction mixture was heated at 90° C. for 15 h. The reaction mixture was worked up with EtOAc. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, filtered off, and concentrated in vacuo. The crude product was purified by flash chromatography (gradient EtOAc in heptanes) yielding 5-(3,6-dihydro-2H-pyran-4-yl)pyrazin-2-amine in 57% yield. LCMS (m/z): 178.1 (MH+), 0.34 min; 1H NMR (400 MHz, CDCl3) δ ppm 8.17-8.03 (m, 1H), 8.04-7.88 (m, 1H), 6.57-6.41 (m, 1H), 4.68-4.42 (m, 2H), 4.42-4.29 (m, 2H), 4.06-3.84 (m, 2H), 2.68-2.47 (m, 2H).

Workup

washThe organic layer was washed with water and brine
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered off
concentrationconcentrated in vacuo
customThe crude product was purified by flash chromatography (gradient EtOAc in heptanes)

Sources & evidence

ORD record: ord-c33abf2d6abc4489996868cf34c9e2ad
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242996B2

Reaction notes

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