Piperazine → 1-(5-Bromopyridin-3-yl)-4-methylpiperazine

HRID 1889839Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[NH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.Cl[CH2:16]Cl>>[Br:8][C:6]1[CH:7]=[C:2]([N:9]2[CH2:14][CH2:13][N:12]([CH3:16])[CH2:11][CH2:10]2)[CH:3]=[N:4][CH:5]=1

Participants

Reactant 3

HCID 4837Piperazine

HCID 6344Dichloromethane

HCID 693693,5-Dibromopyridine

Product 1

HCID 534853141-(5-Bromopyridin-3-yl)-4-methylpiperazine

Conditions

Temperature: 180 °C

Procedure

1-(5-Bromo-pyridin-3-yl)-4-methyl-piperazine was prepared from 3,5-dibromo-pyridine (1.00 g, 4.22 mmol) and piperazine, 1-methyl-(0.936 mL, 8.44 mmol) which were combined and heated in a microwave vial to 180° C. for 2 hours. The reaction mixture was taken up in dichloromethane and purified by silica gel chromatography 0-10% methanol in dichloromethane to afford a clear oil (37%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.20 (s, 1H), 8.11 (s, 1H), 7.29 (m, 1H), 3.25 (bm, 4H), 2.58 (bm, 4H), 2.35 (s, 3H). 108b) [5-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyrazin-2-yl]-[5-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-amine was prepared from 5-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyrazin-2-ylamine and 1-(5-bromo-pyridin-3-yl)-4-methyl-piperazine in a manner analogous to Step 2d and was isolated as an off-white lyophilate (4% yield). 1H NMR (400 MHz, CDCl3, δ, ppm): 10.5 (bs, 1H), 9.86 (bs, 1H), 9.22 (s, 1H), 8.49 (s, 1H), 8.40 (d, J=7.9 Hz, 2H), 8.35 (s, 1H), 8.19 (d, J=7.6 Hz, 2H), 8.05 (d, J=16.5 Hz, 2H), 3.84 (bm, 2H), 3.55 (bm, 2H), 3.38 (s, 3H), 3.20 (bm, 2H), 3.09 (bm, 2H), 2.88 (s, 3H). MS=465.1 (MH)+.

Workup

custompurified by silica gel chromatography 0-10% methanol in dichloromethane

Sources & evidence

ORD record: ord-c9c9f3c9c551428c8df387d33d815fb7
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08501936B2

Reaction notes

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