Water → 8-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene

HRID 886201Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][CH:10]=[C:11]([C:13]3[N:17]([CH:18]([CH3:20])[CH3:19])[N:16]=[CH:15][N:14]=3)[N:12]=2)=[C:4](F)[CH:3]=1.C1(=O)O[CH2:25][CH2:24][O:23]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]3[N:9]([CH:10]=[C:11]([C:13]4[N:17]([CH:18]([CH3:20])[CH3:19])[N:16]=[CH:15][N:14]=4)[N:12]=3)[CH2:25][CH2:24][O:23][C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of 5-[2-(4-bromo-2-fluoro-phenyl)-1H-imidazol-4-yl]-1-isopropyl-1H-[1,2,4]triazole (10.0 g, 28.6 mmol) in DMF (100 mL) was treated with ethylene carbonate (5.3 g, 60.1 mmol) and cesium carbonate (13.9 g, 42.5 mmol) and then heated at 100° C. for 72 h. Further cesium carbonate (9.0 g, 27.5 mmol) and water (0.5 mL) were added and heating continued for 24 h before concentrating the reaction mixture in vacuo. The resultant residue was partitioned between DCM and water, the organic layer was isolated, washed with water then brine, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, 1% MeOH in DCM) to give 194 as an off-white solid (5.78 g, 58%). 1H NMR δ (ppm) (CDCl3): 8.04 (1H, s), 7.83 (1H, s), 7.50-7.38 (3H, m), 5.93-5.84 (1H, m), 4.07-4.02 (2H, m), 3.93-3.88 (2H, m), 1.53-1.46 (6H, m)

Workup

temperatureheating
concentrationbefore concentrating the reaction mixture in vacuo
customThe resultant residue was partitioned between DCM and water
customthe organic layer was isolated
washwashed with water
dry with materialbrine, dried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-02da712ac494490089e7f670f45bfe2b
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08242104B2

Reaction notes

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