Triethylamine → 6-Chloro-2-[[4-(4-fluorophenyl)-1-piperazinyl]methyl]-imidazo[1,2-a]pyridine

HRID 1416252Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([CH2:11]Cl)[N:10]=2)[CH:7]=1.[F:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[CH:16][CH:15]=1.C(N(CC)CC)C>C(O)CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([CH2:11][N:23]3[CH2:22][CH2:21][N:20]([C:17]4[CH:16]=[CH:15][C:14]([F:13])=[CH:19][CH:18]=4)[CH2:25][CH2:24]3)[N:10]=2)[CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 2-(chloromethyl)-6-chloroimidazo[1,2-a]pyridine (Example 4, Step 1; 0.50 g), 1-(4-fluorophenyl)piperazine (Aldrich; 0.471 g), triethylamine (0.277 g), and ethylene glycol (2 mL) is stirred at 80° C. for 1.3 h. After cooling, the mixture is partitioned between dichloromethane and aq. sodium bicarbonate. The organic layers are dried over sodium sulfate and the filtrate is concentrated under reduced pressure. The residue is chromatographed on silica gel using methanol/dichloromethane (2/98) and the appropriate fractions are combined and concentrated. The resulting material is crystallized from dichloromethane/hexane to give 0.66 g of the title compound; mp 129.5-131° C.; MS m/z at 344; IR (mineral oil) 1511, 1236, 1330, 1325, 825 cm-1; 1 H NMR (CDCl3) δ2.74, 3.15, 6.86-6.98, 7.13, 7.52, 7.54, 8.14.

Workup

temperatureAfter cooling
customthe mixture is partitioned between dichloromethane and aq. sodium bicarbonate
dry with materialThe organic layers are dried over sodium sulfate
concentrationthe filtrate is concentrated under reduced pressure
customThe residue is chromatographed on silica gel
concentrationconcentrated
customThe resulting material is crystallized from dichloromethane/hexane

Sources & evidence

ORD record: ord-7f6fbb05510c4460bc7c44b5446dd088
Source dataset: uspto-grants-1999_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05912246

Reaction notes

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