1-Methylpiperazine → 1-(5-Bromo-1,3-thiazol-2-yl)-4-methylpiperazine

HRID 1926308Notes

Reaction equation

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

Participants

Conditions

Temperature: 110 °C

Procedure

A solution of 2,5-dibromothiazole (1.000 g, 4.116 mmol) in DIPEA (3.00 mL) was charged with 1-methylpiperazine (0.457 mL, 4.12 mmol) and heated to 110° C. for 3 h then an additional 48 h at rt. The reaction mixture was partitioned between CHCl3 and H2O, and the layers were separated. The aqueous layer was re-extracted with CHCl3 (3×) and the combined organic fractions were dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by chromatography on silica gel [eluting with 5% EtOAc in CHCl3→20% EtOAc in CHCl3] resulting in the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3): δ=2.34 (s, 3H), 2.48-2.56 (m, 4H), 3.42-3.51 (m, 4H), 7.07 (s, 1H). MS (ES+): m/z=262.09/264.06 (51/49) [MH+]. HPLC: tR=1.57 & 0.53 min (peak splitting; ZQ2, polar—5 min).

Workup

customan additional 48 h
customat rt
customThe reaction mixture was partitioned between CHCl3 and H2O
customthe layers were separated
extractionThe aqueous layer was re-extracted with CHCl3 (3×)
dry with materialthe combined organic fractions were dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude material was purified by chromatography on silica gel [eluting with 5% EtOAc in CHCl3→20% EtOAc in CHCl3]

Sources & evidence

ORD record: ord-267ff5e92ee948428ad7f5bad2fdd830
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178668B2

Reaction notes

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