Cesium carbonate → 1-(5-Bromopyridin-3-yl)-4-methylpiperazine

HRID 1892232Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:57][N:58]1[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]1>O1CCOCC1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:8][C:6]1[CH:7]=[C:2]([N:61]2[CH2:62][CH2:63][N:58]([CH3:57])[CH2:59][CH2:60]2)[CH:3]=[N:4][CH:5]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To a suspension of 3,5-dibromopyridine (0.30 g, 4.6 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (57 mg, 0.098 mmol), tris(dibenzylideneacetone)dipalladium (0) (32 mg, 0.035 mmol) and cesium carbonate (830 mg, 2.5 mmol) in 1,4-dioxane (4.0 mL) in a sealed r×n vessel was added 1-methylpiperazine (0.170 mL, 1.5 mmol) under argon. The reaction mixture was heated for 30 min in a microwave reactor, at 150° C. The reaction mixture was diluted with EtOAc (50 mL), washed with brine and water, dried over Na2SO4, then filtered and concentrated. The crude reaction product was purified by column chromatography to give 1-(5-bromopyridin-3-yl)-4-methylpiperazine (0.13 g, 39%) as a brown oil. LCMS (FA): Rt=1.03 min, m/z=258.0 (M+H).

Workup

washwashed with brine and water
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude reaction product
customwas purified by column chromatography

Sources & evidence

ORD record: ord-66e1856638934d1ea88218b4c89f146b
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507667B2

Reaction notes

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